Physical activity and exercise

مَا تَذَرُ مِن شَيۡءٍ أَتَتۡ عَلَيۡهِ إِلَّا جَعَلَتۡهُ كَٱلرَّمِيمِ

and it reduced everything it came up against to shreds

قَالَ قَآئِلࣱ مِّنۡهُمۡ لَا تَقۡتُلُواْ يُوسُفَ وَأَلۡقُوهُ فِي غَيَٰبَتِ ٱلۡجُبِّ يَلۡتَقِطۡهُ بَعۡضُ ٱلسَّيَّارَةِ إِن كُنتُمۡ فَٰعِلِينَ

[Another of them] said, ‘Do not kill Joseph, but, if you must, throw him into the hidden depths of a well where some caravan may pick him up.’

ٱذۡهَبُواْ بِقَمِيصِي هَٰذَا فَأَلۡقُوهُ عَلَىٰ وَجۡهِ أَبِي يَأۡتِ بَصِيرࣰ ا وَأۡتُونِي بِأَهۡلِكُمۡ أَجۡمَعِينَ

Take my shirt and lay it over my father’s face: he will recover his sight. Then bring your whole family back to me.’

وَمِنَ ٱلنَّاسِ مَن يَتَّخِذُ مِن دُونِ ٱللَّهِ أَندَادࣰ ا يُحِبُّونَهُمۡ كَحُبِّ ٱللَّهِۖ وَٱلَّذِينَ ءَامَنُوٓاْ أَشَدُّ حُبࣰّ ا لِّلَّهِۗ وَلَوۡ يَرَى ٱلَّذِينَ ظَلَمُوٓاْ إِذۡ يَرَوۡنَ ٱلۡعَذَابَ أَنَّ ٱلۡقُوَّةَ لِلَّهِ جَمِيعࣰ ا وَأَنَّ ٱللَّهَ شَدِيدُ ٱلۡعَذَابِ

Even so, there are some who choose to worship others besides God as rivals to Him, loving them with the love due to God, but the believers have greater love for God. If only the idolaters could see- as they will see when they face the torment- that all power belongs to God, and that God punishes severely

۞إِنَّ قَٰرُونَ كَانَ مِن قَوۡمِ مُوسَىٰ فَبَغَىٰ عَلَيۡهِمۡۖ وَءَاتَيۡنَٰهُ مِنَ ٱلۡكُنُوزِ مَآ إِنَّ مَفَاتِحَهُۥ لَتَنُوٓأُ بِٱلۡعُصۡبَةِ أُوْلِي ٱلۡقُوَّةِ إِذۡ قَالَ لَهُۥ قَوۡمُهُۥ لَا تَفۡرَحۡۖ إِنَّ ٱللَّهَ لَا يُحِبُّ ٱلۡفَرِحِينَ

Qarun was one of Moses’ people, but he oppressed them. We had given him such treasures that even their keys would have weighed down a whole company of strong men. His people said to him, ‘Do not gloat, for God does not like people who gloat

قَالُواْ ٱبۡنُواْ لَهُۥ بُنۡيَٰنࣰ ا فَأَلۡقُوهُ فِي ٱلۡجَحِيمِ

They said, ‘Build a pyre and throw him into the blazing fire.’

Go with this shirt of mine and cast it upon the face of my father so that he may come to seeing. Joseph said, " Take my shirt to Jacob, for his pain has not ceased from the time he saw the shirt stained with the wolf's blood. The balm will also be my shirt. " When they took the shirt from Egypt, the morning breeze was commanded to take the shirt's scent to Jacob's nostrils so that, before Joseph's messenger could give the good news, he would receive it from the Real's mes- senger and recognize the Real's perfect gentleness and favor toward him. According to the tasting of the recognizers, this is the divine breeze that wanders furtively around the world to the doors of the breasts of the faithful and the tawḤīd-voicers to see where there may be a limpid breast and an empty secret core in which to dwell. Her love came to me before I knew love- it came across a carefree heart and took poss

Among the people are some who take peers apart from God, loving them as if loving God. And those who have faith are more intense in love for God. If this were the only verse in the whole Qur'an about the faithful and God's friends, their eminence and honor would be complete, for the Lord of the Worlds is saying, “They love Me intensely and more completely than the unbelievers love their objects of worship.” Do you not see that every once in a while the unbelievers set up another idol and take up another object of worship. Like poor people, they are content with something carved of wood. Then, when they can, they take down the wooden one and make another from silver or gold. If their love for their object of wor- ship is real, why do they turn away from it toward another? They say that a man met a woman recognizer, and her beauty exercised its influence over his heart. He said, “'My all i

It did not leave anything any soul or property that it came upon without making it like decayed bones like something that is withered and in scattered pieces.

And in Musa, when We sent him to Fir'awn with a manifest authority (38)But (he) turned away along with his hosts, and said: "A sorcerer or a madman. (39)So We took him and his armies, and dumped them into the sea (Yamm), for he was blameworthy (40)And in 'Ad when We sent against them the barren wind (41)It spared nothing that it reached, but blew it into broken spreads of rotten ruins (42)And in Thamud, when they were told: "Enjoy yourselves for a while! (43)But they insolently defied the command of their Lord, so the Sa'iqah overtook them while they were looking (44)Then they were unable to rise up, nor could they help themselves (45)(So were) the people of Nuh before them. Verily, they were a people who were rebellious (46) Lessons from the Destruction of Fir'awn, 'Ad, Thamud, and the People of Nuh Allah the Exalted said, وَفِي مُوسَىٰ إِذْ أَرْسَلْنَاهُ إِلَىٰ فِرْعَوْنَ بِسُلْطَان

One of them namely Judah said ‘Do not kill Joseph but cast him throw him into the bottom of a well ghayābat al-jubb is the darkest recess of a well; a variant reading has the plural ghayābāt so that some caravan might pick him up if you are to do anything’ of what you desire in the way of separating Joseph from us so content yourselves with this solution.

Yet there be people who take to themselves compeers idols besides God that is other than God loving them by magnifying them and being subservient to them as God is loved that is as their love of Him; but those who believe love God more ardently than those who love their compeers because the former never reject God whereas the latter when faced with hardship soon abandon those compeers for God; If he if you O Muhammad (s) were to see those who did evil by taking to themselves compeers when idh here denotes idhā they see read either as active yarawna ‘they see’ or passive yurawna ‘they are made to see’ the chastisement you would see a grave sight that this is because the might the power and the vanquishing altogether a circumstantial qualifier belongs to God and that God is terrible in chastisement according to one reading the person listening to the verse governs the verb yarā ‘he sees’ a

حَدَّثَنَا أَحْمَدُ بْنُ مَنِيعٍ، حَدَّثَنَا يَزِيدُ بْنُ هَارُونَ، حَدَّثَنَا الْحَجَّاجُ، عَنْ مَكْحُولٍ، عَنْ أَبِي ثَعْلَبَةَ، وَالْحَجَّاجُ، عَنِ الْوَلِيدِ بْنِ أَبِي مَالِكٍ، عَنْ عَائِذِ اللَّهِ بْنِ عَبْدِ اللَّهِ، أَنَّهُ سَمِعَ أَبَا ثَعْلَبَةَ الْخُشَنِيَّ، قَالَ قُلْتُ يَا رَسُولَ اللَّهِ إِنَّا أَهْلُ صَيْدٍ ‏.‏ قَالَ ‏"‏ إِذَا أَرْسَلْتَ كَلْبَكَ وَذَكَرْتَ اسْمَ اللَّهِ عَلَيْهِ فَأَمْسَكَ عَلَيْكَ فَكُلْ ‏"‏ ‏.‏ قُلْتُ وَإِنْ قَتَلَ قَالَ ‏"‏ وَإِنْ قَتَلَ ‏"‏ ‏.‏ قُلْتُ إِنَّا أَهْلُ رَمْىٍ ‏.‏ قَالَ ‏"‏ مَا رَدَّتْ عَلَيْكَ قَوْسُكَ فَكُلْ ‏"‏ ‏.‏ قَالَ قُلْتُ إِنَّا أَهْلُ سَفَرٍ نَمُرُّ بِالْيَهُودِ وَالنَّصَارَى وَالْمَجُوسِ فَلاَ نَجِدُ غَيْرَ آنِيَتِهِمْ ‏.‏ قَالَ ‏"‏ فَإِنْ لَمْ تَجِدُوا غَيْرَهَا فَاغْسِلُوهَا بِالْمَاءِ ثُمَّ كُلُوا فِيهَا وَاشْرَبُوا ‏"‏ ‏.‏ قَالَ وَفِي الْبَابِ عَنْ عَدِيِّ بْنِ حَاتِمٍ ‏.‏ قَالَ أَبُو عِيسَى هَذَا حَدِيثٌ حَسَنٌ صَحِيحٌ ‏.‏ وَعَائِذُ اللَّهِ بْنُ عَبْدِ اللَّهِ هُوَ أَبُو إِدْرِيسَ الْخَوْلاَنِيُّ وَاسْمُ أَبِي ثَعْلَبَةَ الْخُشَنِيِّ جُرْثُومٌ وَيُقَالُ جُرْثُمُ بْنُ نَاشِرٍ وَيُقَالُ ابْنُ قَيْسٍ ‏.‏

Narrated Abu Tha'labah Al-Khushani:"I said: 'O Messenger of Allah! We are a people who hunt.' He said: 'If you send your dog and you mentioned the Name of Allah upon it, and he catches something for you, then eat it.' I said: 'Even if he kills it?' He said: 'Even if he kills it.' I said: 'We are a people who shoot (at game).' He said: 'What you catch with your bow, then eat it.'" He said: "Then I said:'Indeed we are a people who travel. We come across Jews, Christians, and Zoroastrians, and we do not find vessels other than theirs.' He said: 'If you do not find other than them, then wash them with water, then eat and drink from it

أَخْبَرَنَا أَحْمَدُ بْنُ عَبْدِ الْوَاحِدِ، قَالَ حَدَّثَنَا مَرْوَانُ، - وَهُوَ ابْنُ مُحَمَّدٍ - قَالَ حَدَّثَنَا خَالِدُ بْنُ يَزِيدَ بْنِ صَالِحِ بْنِ صَبِيحٍ الْمُرِّيُّ، قَالَ حَدَّثَنَا إِبْرَاهِيمُ بْنُ أَبِي عَبْلَةَ، عَنِ الْوَلِيدِ بْنِ عَبْدِ الرَّحْمَنِ الْجُرَشِيِّ، عَنْ جُبَيْرِ بْنِ نُفَيْرٍ، عَنْ سَلَمَةَ بْنِ نُفَيْلٍ الْكِنْدِيِّ، قَالَ كُنْتُ جَالِسًا عِنْدَ رَسُولِ اللَّهِ صلى الله عليه وسلم فَقَالَ رَجُلٌ يَا رَسُولَ اللَّهِ أَذَالَ النَّاسُ الْخَيْلَ وَوَضَعُوا السِّلاَحَ وَقَالُوا لاَ جِهَادَ قَدْ وَضَعَتِ الْحَرْبُ أَوْزَارَهَا فَأَقْبَلَ رَسُولُ اللَّهِ صلى الله عليه وسلم بِوَجْهِهِ وَقَالَ ‏ "‏ كَذَبُوا الآنَ الآنَ جَاءَ الْقِتَالُ وَلاَ يَزَالُ مِنْ أُمَّتِي أُمَّةٌ يُقَاتِلُونَ عَلَى الْحَقِّ وَيُزِيغُ اللَّهُ لَهُمْ قُلُوبَ أَقْوَامٍ وَيَرْزُقُهُمْ مِنْهُمْ حَتَّى تَقُومَ السَّاعَةُ وَحَتَّى يَأْتِيَ وَعْدُ اللَّهِ وَالْخَيْلُ مَعْقُودٌ فِي نَوَاصِيهَا الْخَيْرُ إِلَى يَوْمِ الْقِيَامَةِ وَهُوَ يُوحَى إِلَىَّ أَنِّي مَقْبُوضٌ غَيْرَ مُلَبَّثٍ وَأَنْتُمْ تَتَّبِعُونِي أَفْنَادًا يَضْرِبُ بَعْضُكُمْ رِقَابَ بَعْضٍ وَعُقْرُ دَارِ الْمُؤْمِنِينَ الشَّامُ ‏"‏ ‏.‏

It was narrated that Salamah bin Nufail Al-Kindi said:"I was sitting with the Messenger of Allah when a man said: 'O Messenger of Allah! The people have lost interest in horses and put down their weapons, and they say there is no Jihad, and that war has ended.' The Messenger of Allah turned to face him and said: 'They are lying, now the fighting is to come. There will always be a group among my Ummah who will fight for the truth, for whom Allah will cause some people to deviate, and grant them provision from them, until the Hour begins and until the promise of Allah comes. Goodness is tied to the forelocks of horses until the Day of Resurrection. It has been revealed to me that I am going to die and will not stay long, and you will follow me group after group, striking one another's necks. And the place of safety for the believers is Ash-Sham

أَخْبَرَنَا عَمْرُو بْنُ يَحْيَى بْنِ الْحَارِثِ، قَالَ حَدَّثَنَا مَحْبُوبُ بْنُ مُوسَى، قَالَ حَدَّثَنَا أَبُو إِسْحَاقَ، - يَعْنِي الْفَزَارِيَّ - عَنْ سُهَيْلِ بْنِ أَبِي صَالِحٍ، عَنْ أَبِيهِ، عَنْ أَبِي هُرَيْرَةَ، قَالَ قَالَ رَسُولُ اللَّهِ صلى الله عليه وسلم ‏ "‏ الْخَيْلُ مَعْقُودٌ فِي نَوَاصِيهَا الْخَيْرُ إِلَى يَوْمِ الْقِيَامَةِ الْخَيْلُ ثَلاَثَةٌ فَهِيَ لِرَجُلٍ أَجْرٌ وَهِيَ لِرَجُلٍ سَتْرٌ وَهِيَ عَلَى رَجُلٍ وِزْرٌ فَأَمَّا الَّذِي هِيَ لَهُ أَجْرٌ فَالَّذِي يَحْتَبِسُهَا فِي سَبِيلِ اللَّهِ فَيَتَّخِذُهَا لَهُ وَلاَ تُغَيِّبُ فِي بُطُونِهَا شَيْئًا إِلاَّ كُتِبَ لَهُ بِكُلِّ شَىْءٍ غَيَّبَتْ فِي بُطُونِهَا أَجْرٌ وَلَوْ عَرَضَتْ لَهُ مَرْجٌ ‏"‏ ‏.‏ وَسَاقَ الْحَدِيثَ ‏.‏

It was narrated that Abu Hurairah said:"The Messenger of Allah said: 'There is goodness tied to the forelocks of horses until the Day of Resurrection. And horses are of three types: Those that bring reward to man, those that are a means of protection for a man, and those that are a burden (of sin) for a man. As for those that bring reward, they are kept for the cause of Allah and for Jihad. No fodder enters their stomach but for everything that enters their stomachs, reward is written for him, even if he puts them out to pasture.'" And he quoted the Hadith

حَدَّثَنَا نَصْرُ بْنُ عَلِيٍّ الْجَهْضَمِيُّ، حَدَّثَنَا الْمُعْتَمِرُ بْنُ سُلَيْمَانَ، عَنْ أَبِيهِ، عَنْ أَبِي إِسْحَاقَ، عَنِ الْبَرَاءِ بْنِ عَازِبٍ، أَنَّ رَسُولَ اللَّهِ صلى الله عليه وسلم قَالَ ‏"‏ ائْتُونِي بِالْكَتِفِ أَوِ اللَّوْحِ ‏"‏ ‏.‏ فَكَتَبَ ‏:‏ ‏(‏ لاَ يَسْتَوِي الْقَاعِدُونَ مِنَ الْمُؤْمِنِينَ ‏)‏ وَعَمْرُو بْنُ أُمِّ مَكْتُومٍ خَلْفَ ظَهْرِهِ فَقَالَ هَلْ لِي مِنْ رُخْصَةٍ فَنَزَلَتْ ‏:‏ ‏(‏ غَيْرُ أُولِي الضَّرَرِ ‏)‏ ‏.‏ وَفِي الْبَابِ عَنِ ابْنِ عَبَّاسٍ وَجَابِرٍ وَزَيْدِ بْنِ ثَابِتٍ ‏.‏ وَهَذَا حَدِيثٌ حَسَنٌ صَحِيحٌ وَهُوَ حَدِيثٌ غَرِيبٌ مِنْ حَدِيثِ سُلَيْمَانَ التَّيْمِيِّ عَنْ أَبِي إِسْحَاقَ ‏.‏ وَقَدْ رَوَى شُعْبَةُ وَالثَّوْرِيُّ عَنْ أَبِي إِسْحَاقَ هَذَا الْحَدِيثَ ‏

Narrated Al-Bara' bin 'Azib: That the Messenger of Allah (ﷺ) said: "Bring me a shoulder blade or tablet." Then he wrote: Not equal are those of believers who sit. 'Amr bin Umm Maktum who was behind him said: "Is there an exemption for me?" So the following was revealed: Except those who are disabled. There are narrations on this topic from Ibn 'Abbas, Jabir and Zaid bin Thabit. This Hadith is Hasan Sahih and it is a Hadith that is Gharib from the narration of Sulaiman At-Taimi from Abu Ishaq. And Shu'bah and Ath-Thawri reported this Hadith from Abu Ishaq

حَدَّثَنَا مُحَمَّدُ بْنُ بَشَّارٍ، حَدَّثَنَا يَحْيَى بْنُ سَعِيدٍ، عَنْ سُفْيَانَ، وَشُعْبَةَ، عَنْ حَبِيبِ بْنِ أَبِي ثَابِتٍ، عَنْ أَبِي الْعَبَّاسِ، عَنْ عَبْدِ اللَّهِ بْنِ عَمْرٍو، قَالَ جَاءَ رَجُلٌ إِلَى النَّبِيِّ صلى الله عليه وسلم يَسْتَأْذِنُهُ فِي الْجِهَادِ فَقَالَ ‏"‏ أَلَكَ وَالِدَانِ ‏"‏ ‏.‏ قَالَ نَعَمْ ‏.‏ قَالَ ‏"‏ فَفِيهِمَا فَجَاهِدْ ‏"‏ ‏.‏ قَالَ أَبُو عِيسَى وَفِي الْبَابِ عَنِ ابْنِ عَبَّاسٍ ‏.‏ وَهَذَا حَدِيثٌ حَسَنٌ صَحِيحٌ ‏.‏ وَأَبُو الْعَبَّاسِ هُوَ الشَّاعِرُ الأَعْمَى الْمَكِّيُّ وَاسْمُهُ السَّائِبُ بْنُ فَرُّوخَ ‏.‏

Narrated 'Abdullah bin 'Umar: A man came to Prophet (ﷺ) seeking permission to go for Jihad. So he said: 'Do you have parents (living)? ' He said: 'Yes.' He said: 'Then it is for them that you should perform Jihad.'" [Abu 'Eisa said:] There is something on this topic from Ibn 'Abbas. This Hadith is Hasan Sahih. (One of the narrators) Abul-Abbas is the blind (Al-A'ma) poet (Ash-Sha'ir), from Makkah, and his name is As-Sa'ab bin Farrukh

وصفات الفعل والقدرة والتفرد بالضر والنفع والعطاء والمنع ونفوذ المشيئة وكمال القوة وتدبير أمر الخليقة أخص باسم الرب

فمنشأ الغلط التسوية بين المشيئة والمحبة واعتقادهم وجوب الرضا بالقضاء ونحن نبين ما في الفصلين إن شاء الله تعالى فإن القوة لله جميعا

المثال الأول أن نقول مثل نفس الإنسان في بدنه أعني بالنفس اللطيفة المذكورة كمثل ملك في مدينته ومملكته فإن البدن مملكة النفس وعالمها ومستقرها ومدينتها وجوارحها وقواها بمنزلة الصناع والعملة والقوة العقلية المفكرة له كالمشير الناصح والوزير العاقل

1332 وعن أبي حماد ويقال أبو سعاد ويقال أبو أسد ويقال أبو عامر ويقال أبو عمرو ويقال أبو الأسود ويقال أبو عبس عقبة بن عامر الجهني رضي الله عنه قال سمعت رسول الله صلى الله عليه وسلم وهو على المنبر يقول وأعدوا لهم ما استطعتم من قوة ألا إن القوة الرمي ألا إن القوة الرمي ألا إن القوة الرمي رواه مسلم

السير في طلبها سير في أرض مسبعة والسباحة فيها سباحة في غدير التمساح المفروح به منها هو عين المحزون عليه آلامها متولدة من لذاتها واحزانها من أفراحها

فهذا وأمثاله من الأسباب مع الانهماك في الشهوات هو الذي سد على الخلق سبيل الاستضاءة بأنوار المعرفة والسباحة في بحارها الواسعة فالناس في طلبهم معرفة الله كالمدهوش الذى يضرب به المثل إذا كان راكبا لحماره وهو يطلب حماره والجليات إذا صارت مطلوبة صارت معتاصة

Lack of exercise is a major cause of chronic diseases.: Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause versus treatment; physical activity and inactivity mechanisms differ; gene-environment interaction (including aerobic training adaptations, personalized medicine, and co-twin physic

High-Intensity Interval Training and Isocaloric Moderate-Intensity Continuous Training Result in Similar Improvements in Body Composition and Fitness in Obese Individuals.: This study aimed to determine the effects of 12 weeks of isocaloric programs of high-intensity intermittent training (HIIT) or moderate-intensity continuous training (MICT) or a short-duration HIIT (1/2HIIT) inducing only half the energy deficit on a cycle ergometer, on body weight and composition, cardiovascular fitness, resting metabolism rate (RMR), respiratory exchange ratio (RER), nonexercise physical activity (PA) levels and fasting and postprandial insulin response in sedentary obese indi

Web-based intervention to promote physical activity by sedentary older adults: randomized controlled trial.: Background: Physical activity (PA) for older adults has well-documented physical and cognitive benefits, but most seniors do not meet recommended guidelines for PA, and interventions are lacking. Objectives: This study evaluated the efficacy of a 12-week Internet intervention to help sedentary older adults over 55 years of age adopt and maintain an exercise regimen. Methods: A total of 368 sedentary men and women (M=60.3; SD 4.9) were recruited, screened, and assessed online. They were randomize

Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: systematic review and meta-analysis.: Objective: To assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. Data sources: Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. Population: sedentary individ

Physical activity patterns among South-Asian adults: a systematic review.: Physical activity (PA) has many beneficial physical and mental health effects. Physical inactivity is considered the fourth leading risk factor for global mortality. At present there are no systematic reviews on PA patterns among South Asian adults residing in the region. The present study aims to systematically evaluate studies on PA patterns in South Asian countries. A five-staged comprehensive search of the literature was conducted in Medline, Web of Science and SciVerse Scopus using keywords

Reducing the decline in physical activity during pregnancy: a systematic review of behaviour change interventions.: Purpose: Physical activity (PA) typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to re

A role for orexin in central vestibular motor control.

The absence of orexin results in narcolepsy-cataplexy. While the function of the central orexinergic system in sleep regulation has been well studied, the role of orexin in motor control is largely unknown. Here, we show that orexin-A acts via OX(1) and OX(2) receptors to directly depolarize neurons in the rat lateral vestibular nucleus (LVN), a subcortical motor center, and enhance their sensitivity. A dual ionic mechanism involving both Na+-Ca²+ exchangers and inward rectifier K+ channels underlies these effects. Furthermore, orexin-A regulates central vestibular-mediated posture, motor balance and negative geotaxis. Orexin is critical when an animal is facing a major motor challenge as opposed to during rest and general movements. Therefore, orexin participates not only in sleep and emotion (nonsomatic) but also in motor (somatic) regulation, suggesting that the central orexinergic sy…

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Reduced anxiety-like behavior and central neurochemical change in germ-free mice.

Background: There is increasing interest in the gut-brain axis and the role intestinal microbiota may play in communication between these two systems. Acquisition of intestinal microbiota in the immediate postnatal period has a defining impact on the development and function of the gastrointestinal, immune, neuroendocrine and metabolic systems. For example, the presence of gut microbiota regulates the set point for hypothalamic-pituitary-adrenal (HPA) axis activity. Methods: We investigated basal behavior of adult germ-free (GF), Swiss Webster female mice in the elevated plus maze (EPM) and compared this to conventionally reared specific pathogen free (SPF) mice. Additionally, we measured brain mRNA expression of genes implicated in anxiety and stress-reactivity. Key results: Germ-free mice, compared to SPF mice, exhibited basal behavior in the EPM that can be interpreted as anxiolytic. …

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A time-dependent history of mood disorders in a murine model of neuropathic pain.

Background: Chronic pain is clinically associated with the development of affective disorders. However, studies in animal models of neuropathic pain are contradictory and the relationship with mood disorders remains unclear. In this study, we aimed to characterize the affective consequences of neuropathic pain over time and to study potential underlying mechanisms. Methods: Neuropathic pain was induced by inserting a polyethylene cuff around the main branch of the right sciatic nerve in C57BL/6J mice. Anxiety- and depression-related behaviors were assessed over 2 months, using a battery of tests, such as elevated plus maze, marble burying, novelty suppressed feeding, splash test, and forced swimming test. Plasma corticosterone levels were assessed by radioimmunoassay. We also investigated changes in cyclic adenosine monophosphate response element (CRE) activity using CRE-LacZ transgenic …

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Resilience and reduced c-Fos expression in P2X7 receptor knockout mice exposed to repeated forced swim test.

There is considerable evidence suggesting genetic factors play an important role in the pathophysiology of depression, possibly by increasing susceptibility to repeated environmental stressors. Recent linkage studies have associated a polymorphism of the gene coding for the P2X7 receptor (P2X7R) with both major depressive disorder and bipolar disorder. Here we assessed whether P2X7 deletion affected the behavioural and neural response to repeated stress. P2X7R knockout (P2X7-/-) mice were subjected to the forced swim test for three consecutive days and neuronal activation in response to the third exposure was assessed using c-Fos immunohistochemistry. In addition, anxiety was evaluated in another group of P2X7-/- mice using the elevated plus maze (EPM) and light dark emergence (LDE) tests. Equivalent levels of immobility were observed in P2X7-/- mice and wild-type (WT) mice on the first …

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Development of the brain's default mode network from wakefulness to slow wave sleep.

Falling asleep is paralleled by a loss of conscious awareness and reduced capacity to process external stimuli. Little is known on sleep-associated changes of spontaneously synchronized anatomical networks as detected by resting-state functional magnetic resonance imaging (rs-fMRI). We employed functional connectivity analysis of rs-fMRI series obtained from 25 healthy participants, covering all non-rapid eye movement (NREM) sleep stages. We focused on the default mode network (DMN) and its anticorrelated network (ACN) that are involved in internal and external awareness during wakefulness. Using independent component analysis, cross-correlation analysis (CCA), and intraindividual dynamic network tracking, we found significant changes in DMN/ACN integrity throughout the NREM sleep. With increasing sleep depth, contributions of the posterior cingulate cortex (PCC)/retrosplenial cortex (Rs…

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Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve.

There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, a…

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Prevention and treatment of drug addiction by environmental enrichment.

Environmental enrichment (EE) has been shown to have powerful beneficial effects on a variety of physiological and pathological processes. Accumulating evidence indicates that EE can mimic positive life experiences and prevent the development of drug addiction. More recently, EE has also been shown to eliminate already developed addiction-related behaviors and to reduce the risks of relapse. These preventive and "curative" effects of EE are associated with dramatic plastic changes in several brain areas such as the hippocampus, the frontal cortex and the striatum. EE alters neurotransmitter systems, produces changes in gene expression and transcription factors, induces chromatin rearrangement, and stimulates hippocampal neurogenesis. Here we review the existent literature on behavioral, neurochemical, cellular and molecular effects of EE and we discuss different possible ways in which EE…

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A single footshock causes long-lasting hypoactivity in unknown environments that is dependent on the development of contextual fear conditioning.

Exposure to a single session of footshocks induces long-lasting inhibition of activity in unknown environments that markedly differ from the shock context. Interestingly, these effects are not necessarily associated to an enhanced anxiety and interpretation of this hypoactivity remains unclear. In the present experiment we further studied this phenomenon in male Sprague-Dawley rats. In a first experiment, a session of three shocks resulted in hypoactivity during exposure, 6-12days later, to three different unknown environments. This altered behaviour was not accompanied by a greater hypothalamic-pituitary-adrenal (HPA) activation, although greater HPA activation paralleling higher levels of freezing was observed in the shock context. In a second experiment we used a single shock and two procedures, one with pre-exposure to the context before the shock and another with immediate shock tha…

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Behavioral and neurochemical effects of chronic L-DOPA treatment on nonmotor sequelae in the hemiparkinsonian rat.

Depression and anxiety are the prevalent nonmotor symptoms that worsen quality of life for Parkinson's disease (PD) patients. Although dopamine (DA) cell loss is a commonly proposed mechanism, the reported efficacy of DA replacement therapy with L-DOPA on affective symptoms is inconsistent. To delineate the effects of DA denervation and chronic L-DOPA treatment on affective behaviors, male Sprague-Dawley rats received unilateral 6-hydroxydopamine or sham lesions and were treated daily with L-DOPA (12 mg/kg+benserazide, 15 mg/kg, subcutaneously) or vehicle (0.9% NaCl, 0.1% ascorbic acid) for 28 days before commencing investigations into anxiety (locomotor chambers, social interaction) and depression-like behaviors (forced swim test) during the OFF phase of L-DOPA. One hour after the final treatments, rats were killed and striatum, prefrontal cortex, hippocampus, and amygdala were analyzed…

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General psychological acceptance and chronic pain: there is more to accept than the pain itself.

An increasing body of research demonstrates that acceptance of pain is significantly associated with the quality of daily functioning in people with chronic pain. The aim of the present study was to examine acceptance more broadly in relation to a wider range of undesirable experiences these people may encounter, such as other physical symptoms, experiences of emotional distress, or distressing thoughts. One hundred forty-four, consecutive, adult patients attending interdisciplinary treatment for chronic pain participated in this study. They completed the Acceptance and Action Questionnaire-II (AAQ-II [Bond F, Hayes SC, Baer RA, Carpenter KM, Orcutt HK, Waltz T, Zettle RD. Preliminary psychometric properties of the Acceptance Action Questionnaire-II: a revised measure of psychological flexibility and acceptance, submitted for publication]), measuring their general psychological acceptanc…

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Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis.

Toll-like receptors (TLRs) are innate immune receptors that have recently emerged as regulators of neuronal survival and developmental neuroplasticity. Adult TLR3-deficient mice exhibited enhanced hippocampus-dependent working memory in the Morris water maze, novel object recognition, and contextual fear-conditioning tasks. In contrast, TLR3-deficient mice demonstrated impaired amygdala-related behavior and anxiety in the cued fear-conditioning, open field, and elevated plus maze tasks. Further, TLR3-deficient mice exhibited increased hippocampal CA1 and dentate gyrus volumes, increased hippocampal neurogenesis, and elevated levels of the AMPA receptor subunit GluR1 in the CA1 region of the hippocampus. In addition, levels of activated forms of the kinase ERK and the transcription factor CREB were elevated in the hippocampus of TLR3-deficient mice, suggesting that constitutive TLR3 signa…

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Early life protein restriction alters dopamine circuitry.

Adverse prenatal environment, such as intrauterine growth retardation (IUGR), increases the risk for negative neurobehavioral outcomes. IUGR, affecting approximately 10% of all US infants, is a known risk factor for attention deficit hyperactivity disorder (ADHD), schizophrenia spectrum disorders and addiction. Mouse dams were fed a protein deficient (8.5% protein) or isocaloric control (18% protein) diet through pregnancy and lactation (a well validated rodent model of IUGR). Dopamine-related gene expression, dopamine content and behavior were examined in adult offspring. IUGR offspring have six to eightfold over-expression of dopamine (DA)-related genes (tyrosine hydroxylase (TH) and dopamine transporter) in brain regions related to reward processing (ventral tegmental area (VTA), nucleus accumbens, prefrontal cortex (PFC)) and homeostatic control (hypothalamus), as well as increased n…

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Evaluating early preventive antipsychotic and antidepressant drug treatment in an infection-based neurodevelopmental mouse model of schizophrenia.

Current pharmacotherapy of schizophrenia remains unsatisfactory with little hope for complete functional restoration in patients once the disease has developed. A preventive approach based on intervention in the prodromal stage of the disease aiming to preserve functional integrity by halting the progress of the disease is therefore extremely attractive. Here, we investigated the effects of preventive antipsychotic or antidepressant drug treatment in a well-established neurodevelopmental mouse model of multiple schizophrenia-related abnormalities. Pregnant mice on gestation day 9 were exposed to the viral mimic polyriboinosinic-polyribocytidylic acid (2 mg/kg, intravenously) or corresponding vehicle treatment, and the resulting offspring from both prenatal treatment conditions were subjected to chronic antipsychotic (haloperidol or clozapine), antidepressant (fluoxetine), or placebo trea…

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Cannabidiol ameliorates cognitive and motor impairments in bile-duct ligated mice via 5-HT1A receptor activation.

Background and purpose: We aimed to demonstrate the involvement of 5-HT(1A) receptors in the therapeutic effect of cannabidiol, a non-psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile-duct ligation (BDL) in mice. Experimental approach: Cannabidiol (5 mg x kg(-1); i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight-arm maze and the open field tests respectively. Hippocampi were analysed by RT-PCR for expression of the genes for tumour necrosis factor-alpha receptor 1, brain-derived neurotrophic factor (BDNF) and 5-HT(1A) receptor. N-(2-(4-(2-methoxy-phenyl)-1-piperazin-1-yl)ethyl)-N-(2-pyridyl) cyclohexanecarboxamide (WAY-100635), a 5-HT(1A) receptor antagonist (0.5 mg x kg(-1)), was co-administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and biliru…

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Residual social, memory and oxytocin-related changes in rats following repeated exposure to γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination.

Rationale: There has been little investigation of the possible lasting adverse effects of γ-hydroxybutyrate (GHB). Objectives: This study aims to study whether GHB produces residual adverse effects on memory and social behaviour in rats and lasting changes in brain monoamines and oxytocin-related gene expression. Methods: Rats received daily intraperitoneal injections of GHB (500 mg/kg), methylenedioxymethamphetamine (MDMA; 5 mg/kg) or their combination (GHB/MDMA) over ten consecutive days. Locomotor activity and body weight were assessed during the dosing period and withdrawal-related anxiety was assessed 24 h after drug cessation. After a washout of 4 weeks, rats were tested on the emergence, social interaction, and object recognition tasks over a 2-week period. Monoamine levels in cortex and striatum, and hypothalamic oxytocin and oxytocin receptor mRNA, were then assessed. Results: M…

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Association between adult attention deficit/hyperactivity disorder and obesity in the US population.

Attention deficit hyperactivity disorder (ADHD) is a neurobehavioral disorder that affects approximately 2.9-4.7% of US adults. Studies have revealed high rates of ADHD (26-61%) in patients seeking weight loss treatment suggesting an association between ADHD and obesity. The objective of the present study was to test the association between ADHD and overweight and obesity in the US population. Cross-sectional data from the Collaborative Psychiatric Epidemiology Surveys were used. Participants were 6,735 US residents (63.9% white; 51.6% female) aged 18-44 years. A retrospective assessment of childhood ADHD and a self-report assessment of adult ADHD were administered. Diagnosis was defined by three categories: never met diagnostic criteria, met full childhood criteria with no current symptoms, and met full childhood criteria with current symptoms. The prevalence of overweight and obesity w…

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Prognostic importance and long-term determinants of self-rated health after initial acute myocardial infarction.

Background: Self-rated health (SRH) is a valid measure of health and its trajectories over time have been found to predict mortality. A better understanding of the determinants of changes in SRH is required, particularly post-myocardial infarction (MI), where rapid changes in health may occur. Objectives: To evaluate the prognostic importance of SRH and the determinants of its long-term trajectory in patients with MI. Patients and methods: Between February 1992 and February 1993, 1521 consecutive patients aged <or=65 years (19% women) discharged from all hospitals in central Israel after initial acute MI were enrolled and followed-up for a mean of 12 years. Extensive data were obtained at study entry, with SRH measured at baseline (retrospective assessment of pre-MI health status) and at 5 and 10 years. Results: Baseline SRH showed a strong graded association with mortality post-MI. The …

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Light-induced activity in the activity box is not aversively motivated and does not show between-trial habituation.

The induction of behaviour by sensory stimuli, i.e. sensorimotor stimulation, is a fundamental aspect of behaviour. Recently, it was found that the presentation of white-light stimuli to a rat in an activity box reliably induces locomotor activity, and, thus, may be able to serve as a paradigm to measure basal, non-aversively motivated sensorimotor processing. However, light can be an aversive stimulus to a rat. In order to test if there is a stressful component in light-induced activity, a retreat-box was introduced into the test-apparatus in experiment 1, so that the animals had the opportunity to escape the light stimuli. It was found, that light-induced activity was also shown, when a retreat-box was available in the activity box, and that light-stimulation did not lead to an increase of entries into or the time spent in the retreat box. Experiment 2 examines the stability of the res…

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Chronic vagus nerve stimulation induces neuronal plasticity in the rat hippocampus.

Vagus nerve stimulation (VNS) is used to treat pharmacotherapy-resistant epilepsy and depression. However, the mechanisms underlying the therapeutic efficacy of VNS remain unclear. We examined the effects of VNS on hippocampal neuronal plasticity and behaviour in rats. Cell proliferation in the hippocampus of rats subjected to acute (3 h) or chronic (1 month) VNS was examined by injection of bromodeoxyuridine (BrdU) and immunohistochemistry. Expression of doublecortin (DCX) and brain-derived neurotrophic factor (BDNF) was evaluated by immunofluorescence staining. The dendritic morphology of DCX+ neurons was measured by Sholl analysis. Our results show that acute VNS induced an increase in the number of BrdU+ cells in the dentate gyrus that was apparent 24 h and 3 wk after treatment. It also induced long-lasting increases in the amount of DCX immunoreactivity and in the number of DCX+ neu…

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Anxiolytic- and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models.

Ketamine, a dissociative anesthetic agent, appears to have rapid antidepressant effects at sub-anesthetic doses in clinically depressed patients. Although promising, these results need to be replicated in double-blind placebo-controlled studies, a strategy thwarted by the psychoactive effects of ketamine, which are obvious to both patients and clinicians. Alternatively, demonstrations of the psychotherapeutic effects of ketamine in animal models are also complicated by ketamine's side-effects on general activity, which have not been routinely measured or taken into account in experimental studies. In this study we found that ketamine decreased "behavioral despair" in the forced swim test, a widely used rats model of antidepressant drug action. This effect was not confounded by side-effects on general activity, and was comparable to that of a standard antidepressant drug, fluoxetine. Inte…

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Cortical and subcortical networks in human secondarily generalized tonic-clonic seizures.

Generalized tonic-clonic seizures are among the most dramatic physiological events in the nervous system. The brain regions involved during partial seizures with secondary generalization have not been thoroughly investigated in humans. We used single photon emission computed tomography (SPECT) to image cerebral blood flow (CBF) changes in 59 secondarily generalized seizures from 53 patients. Images were analysed using statistical parametric mapping to detect cortical and subcortical regions most commonly affected in three different time periods: (i) during the partial seizure phase prior to generalization; (ii) during the generalization period; and (iii) post-ictally. We found that in the pre-generalization period, there were focal CBF increases in the temporal lobe on group analysis, reflecting the most common region of partial seizure onset. During generalization, individual patients h…

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Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin.

Although the tryptophan-degrading enzyme, indoleamine 2,3-dioxygenase (IDO), is a pivotal mediator of inflammation-induced depression, its mechanism of regulation has not yet been investigated in this context. Here, we demonstrate an essential role for interferon (IFN)gamma and tumor necrosis factor (TNF)alpha in the induction of IDO and depressive-like behaviors in response to chronic immune activation. Wild-type (WT) control mice and IFNgammaR(-/-) mice were inoculated with an attenuated form of Mycobacterium bovis, bacille Calmette-Guérin (BCG). Infection with BCG induced an acute episode of sickness that was similar in WT and IFNgammaR(-/-) mice. Increased immobility during the forced swim and tail suspension tests occurred in WT mice 7 d after BCG inoculation but was entirely absent in IFNgammaR(-/-) mice. In WT mice, these indices of depressive-like behavior were associated with ch…

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Reduced midlife physical functioning among never married and childless men: evidence from the 1946 British birth cohort study.

Background and aims: Marital and parental role characteristics are important factors in both men and women's health. Most studies to date have either focused on disease specific outcomes or summary measures of self-reported health rather than using functional tests of performance. The goal of this study is to investigate the extent to which marital and parental role characteristics are associated with midlife physical function. Methods: A prospective birth cohort study was carried out with reference to births that took place in England, Scotland, and Wales during one week in March of 1946. Regular assessment of 1353 men and 1411 women were made from six weeks after birth throughout childhood and adulthood. Handgrip strength, timed chair rising, and standing balance tests at age 53 years were used to calculate an aggregate physical performance score that ranged from 0 (poorest score) to 2…

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Awake replay of remote experiences in the hippocampus.

Hippocampal replay is thought to be essential for the consolidation of event memories in hippocampal-neocortical networks. Replay is present during both sleep and waking behavior, but although sleep replay involves the reactivation of stored representations in the absence of specific sensory inputs, awake replay is thought to depend on sensory input from the current environment. Here, we show that stored representations are reactivated during both waking and sleep replay. We found frequent awake replay of sequences of rat hippocampal place cells from a previous experience. This spatially remote replay was as common as local replay of the current environment and was more robust when the rat had recently been in motion than during extended periods of quiescence. Our results indicate that the hippocampus consistently replays past experiences during brief pauses in waking behavior, suggestin…

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Ablation of adhesion molecule L1 in mice favours Schwann cell proliferation and functional recovery after peripheral nerve injury.

The adhesion molecule L1 is one of the few adhesion molecules known to be beneficial for repair processes in the adult central nervous system of vertebrates by promoting axonal growth and neuronal survival. In the peripheral nervous system, L1 is up-regulated by myelination-competent Schwann cells and regenerating axons after nerve damage but its functional role has remained unknown. Here we tested the hypothesis that L1 is, as in the central nervous system, beneficial for nerve regeneration in the peripheral nervous system by performing combined functional and histological analyses of adult L1-deficient mice (L1y/-) and wild-type (L1y/+) littermates. Contrary to our hypothesis, quantitative video-based motion analysis revealed better locomotor recovery in L1y/- than in L1y/+ mice at 4-12 weeks after transection and surgical repair of the femoral nerve. Motoneuron regeneration in L1y/- m…

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