Altérations cellulaires hippocampiques liées à l'âge et récupération cognitive induite par un enrichissement environnemental chez les souris Tg2576 modèles de la maladie d’Alzheimer

Afin comprendre les mécanismes cellulaires qui sous-tendent le développement de la maladie d'Alzheimer (MA), nous avons utilisé des souris transgéniques (Tg2576) qui développent des altérations phénotypiques mimant certains aspects de la MA. Nous avons révélé qu'au cours du développement de la MA, la neurogenèse hippocampique est altérée chez les jeunes souris Tg2576 et qu'un remodelage du réseau neuronal de l'hippocampe pourrait contribuer aux déficits de mémoire. D'autre part, il a été suggéré que les facteurs environnementaux pourraient diminuer le risque de développer la MA chez l'Homme. L'hypothèse de la "réserve cognitive" propose que les stimulations cognitives induisent des modifications durables du cerveau, le rendant plus résistant à la démence et aux atteintes cellulaires. L'exposition précoce des souris à un environnement enrichi restaure les performances de mémoire et réduit la formation de plaques amyloïdes dans le cerveau.To understand the cellular mechanisms underlying the development of Alzheimer's disease (AD), we used transgenic mice (Tg2576) that develop phenotypic alterations mimicking some aspects of AD. We found that during the development of AD, hippocampal neurogenesis is impaired in young Tg2576 mice and a remodeling of the neural network of the hippocampus may contribute to memory deficits. On the other hand, environmental factors have been suggested to impact the risk and development of AD. The "cognitive reserve" hypothesis proposes protective effects of complex experiences, such as sustained cognitive engagement, against dementia. We found that transient enriched housing of young mice to an enriched environment restores memory performance and decreases senile plaque formation in neo-cortical areas

Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers

Objective: This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. Methods: Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. Results: Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos- positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. Conclusions: Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease

Popularity of carsharing service on the example of Szczecin city for age group 18–25 years

Carsharing jest modelem biznesowym, polegającym na wypożyczaniu samochodów na krótki czas − jest to atrakcyjne dla osób korzystających z auta sporadycznie oraz dla tych, którzy chcieliby mieć samochód określonego typu na konkretną okazję. Celem artykułu jest analiza i ocena popularności usługi wypożyczania samochodu na minuty w wybranej grupie wiekowej.Carsharing is a business model whose goal is to rent a car for a short time. It is attractive for people using the car sporadically and for those who would like to have access to a particular type of car for a specific occasion. The aim of the article is to analyze and evaluate the popularity of a car rental service for minutes, among a selected age group on the example of the city of Szczecin

Altérations cellulaires hippocampiques liées à l'âge et récupération cognitive induite par un enrichissement environnemental chez les souris Tg2576 modèles de la maladie d Alzheimer

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

High fat diet rapidly induces brain-plasticity-related transcriptomic signature in hypothalamus: role in energy homeostasis

Poster board E12 (1 page) ; Session 203 - Food intake regulation 3 - Abstract n° 203.1 - Publication ref.: FENS Abstr., vol.5, 203.1, 2010International audienceWe have investigated the early events that are induced by a hypercaloric hyperlipidic diet in mice. The high fat diet rapidly induced metabolic imbalance, as soon as the first day, which is characterized. by a large increase in energy intake and several others metabolic alterations such as. hypercholesterolemia, and glucose intolerance. However, the diet-induced metabolic imbalance was. fully reversed after a week, suggesting that a physiological adaptive response has been then induced,. probably in order to counteract the deleterious excessive caloric intake in these normal mice. The. hypothalamus, which ensures coordination of endocrine and autonomic functions, and thus long-term. stability of the inner milieu, is of major importance in the control of food intake and energy. homeostasis. Interestingly, the hypothalamus remains "plastic" in adulthood, meaning that neuronal. networks in this structure can undergo functional or morphological remodeling aimed at integrating. modifications in environmental conditions and in physiological states. We hypothesized that brain. plasticity could occur in hypothalamus after the change in diet condition, to re-wire hypothalamic. neuronal networks that control the eating behavior to correctly fit the food intake with the energy. expenditure. By the use of a transcriptomic tool, we observed that high fat diet was associated with. numerous up-regulation of mRNA, markers of brain plasticity as soon as the first day after the change. in diet. This transcriptional modification suggests the initiation of one main feature of brain plasticity. that is synaptogenesis. Interestingly, the kinetics of molecular signature anticipates the food behavior. restoration, suggesting that a causal relation may exist

Early effects of high-fat diet on hypothalamic cell proliferation

International audienceThe hypothalamus is one of the main brain structure involved in the control of. energy homeostasis. Recent reports indicate that hypothalamus exhibits neuroproliferative. potency in adult. Moreover, it has been found that hypothalamic cell. proliferation could be modulated by numerous intrinsic factors such as CNTF, IGF-. 1, bFGF and EGF, and by external and internal conditions such as dehydration,. variation in ambient temperature and during ovarian cycle. Interestingly, experimental. manipulation of neurogenesis can affect body weight. However, whether. nutritional conditions could influence hypothalamic cell proliferation and thereby. modify energy homeostasis is still unknown. To address this question, mice were. subjected to a high fat diet (HFD) for 1 week and hypothalamic cell renewal was. assessed through central chronic infusion of Bromodeoxy-Uridine (BrdU). Using this. approach, we report that hypothalamus constitutively exhibits G2000 BrdUpositive. neo-formed cells per day. This proliferative rate was significantly higher in hypothalamus 3 days after the onset of HFD (+60%) but decreased by 50% on day. 5. To determine whether these HFD-induced modifications of cell renewal were. linked to change in cell proliferation, we counted Ki67 immunoreactive cells. We. found 1937 Ki67 immunoreactive cells in hypothalamus from mice fed with. standard chow. However, the number of such cell was significantly higher in mice. fed with HFD for 1 and 3 days (+30% and 50%, respectively), and returned to basal. value after 5 days. In order to evaluate the role of newborn cells, HFD fed mice were. treated with the anti-mitotic arabinoside cytosine (AraC) for 30 days. Results show. that AraC treatment increased HFD-induced body weight gain, suggesting that. newborn HFD-induced cells produce anorectic function. Altogether these data. demonstrate that a change in diet induces cell proliferation in the hypothalamus. which might be involved in the control of long-term energy homeostasis

Transient enriched housing before amyloidosis onset sustains cognitive improvement in Tg2576 mice

International audienc

Cerebral cell renewal in adult mice controls the onset of obesity.

The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance

Anti-obesity sodium tungstate treatment triggers axonal and glial plasticity in hypothalamic feeding centers.

International audienceOBJECTIVE: This study aims at exploring the effects of sodium tungstate treatment on hypothalamic plasticity, which is known to have an important role in the control of energy metabolism. METHODS: Adult lean and high-fat diet-induced obese mice were orally treated with sodium tungstate. Arcuate and paraventricular nuclei and lateral hypothalamus were separated and subjected to proteomic analysis by DIGE and mass spectrometry. Immunohistochemistry and in vivo magnetic resonance imaging were also performed. RESULTS: Sodium tungstate treatment reduced body weight gain, food intake, and blood glucose and triglyceride levels. These effects were associated with transcriptional and functional changes in the hypothalamus. Proteomic analysis revealed that sodium tungstate modified the expression levels of proteins involved in cell morphology, axonal growth, and tissue remodeling, such as actin, CRMP2 and neurofilaments, and of proteins related to energy metabolism. Moreover, immunohistochemistry studies confirmed results for some targets and further revealed tungstate-dependent regulation of SNAP25 and HPC-1 proteins, suggesting an effect on synaptogenesis as well. Functional test for cell activity based on c-fos-positive cell counting also suggested that sodium tungstate modified hypothalamic basal activity. Finally, in vivo magnetic resonance imaging showed that tungstate treatment can affect neuronal organization in the hypothalamus. CONCLUSIONS: Altogether, these results suggest that sodium tungstate regulates proteins involved in axonal and glial plasticity. The fact that sodium tungstate could modulate hypothalamic plasticity and networks in adulthood makes it a possible and interesting therapeutic strategy not only for obesity management, but also for other neurodegenerative illnesses like Alzheimer's disease