Endogenous hippocampal leptin in mediating strong potentiation by Astaxanthin supplementation for mild exercise-enhanced neurogenesis and memory functions
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE107314 | GEO | 2017/11/25
SECONDARY ACCESSION(S): PRJNA419754
REPOSITORIES: GEO
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Project description:Aerobic exercise is well known to promote neuroplasticity and hippocampal memory. In the developing brain, early-life exercise (ELE) can lead to lasting improvements in hippocampal function, yet molecular mechanisms underlying this phenomenon have not been fully explored. In this study, adolescent transgenic mice harboring the “NuTRAP” (Nuclear tagging and Translating Ribosome Affinity Purification) cassette in Emx1 expressing neurons (“Emx1-NuTRAP” mice) undergo ELE followed by a hippocampal learning task, in order to determine the molecular underpinnings of exercise contributing to improved hippocampal memory performance. We simultaneously isolate and sequence translating mRNA and nuclear chromatin from a single hippocampus in a cell-type specific manner (excitatory neurons), demonstrate validity of our new technical approach, and couple multi-omics sequencing data to evaluate histone modifications H4K8ac and H3K27me3 and their influence on gene expression after ELE. We then evaluate new gene expression – histone modification relationships specifically during hippocampal memory consolidation that may play a critical role in facilitated memory after ELE. Our data reveal novel candidate gene-histone modification interactions and implicate gene regulatory pathways involved in ELE’s impact on hippocampal learning and memory.
2022-10-18 | GSE208633 | GEO
Project description:Aerobic exercise is well known to promote neuroplasticity and hippocampal memory. In the developing brain, early-life exercise (ELE) can lead to lasting improvements in hippocampal function, yet molecular mechanisms underlying this phenomenon have not been fully explored. In this study, adolescent transgenic mice harboring the “NuTRAP” (Nuclear tagging and Translating Ribosome Affinity Purification) cassette in Emx1 expressing neurons (“Emx1-NuTRAP” mice) undergo ELE followed by a hippocampal learning task, in order to determine the molecular underpinnings of exercise contributing to improved hippocampal memory performance. We simultaneously isolate and sequence translating mRNA and nuclear chromatin from a single hippocampus in a cell-type specific manner (excitatory neurons), demonstrate validity of our new technical approach, and couple multi-omics sequencing data to evaluate histone modifications H4K8ac and H3K27me3 and their influence on gene expression after ELE. We then evaluate new gene expression – histone modification relationships specifically during hippocampal memory consolidation that may play a critical role in facilitated memory after ELE. Our data reveal novel candidate gene-histone modification interactions and implicate gene regulatory pathways involved in ELE’s impact on hippocampal learning and memory.
2022-10-18 | GSE208714 | GEO
Project description:We utilized an unbiased RNA-sequencing approach to uncover genes in the dorsal hippocampus that are differentially expressed under conditions where exercise benefits are maintained throughout sedentary delay periods and enable the formation of long-term memory and synaptic plasticity. Engagement in different exercise parameters resulted in a diverse transcriptional profile as defined by differences in the number, pattern, and type of genes up and down-regulated. To identify genes that play a critical role in cognitive enhancement, we next focused our attention on exercise groups that enable robust long-term memory formation under inadequate subthreshold acquisition sessions of the hippocampus-dependent object location memory task. By intersecting up regulated genes when exercise facilitated learning, we identify potential regulators of learning and targets for memory enhancement. We identify a gene coding for a type 1 membrane receptor and kinase for the TGF-β family of signaling molecules, Acvr1c as one of few genes showing upregulation in conditions where exercise enabled the formation of long-term memory, indicating a gate-type role for Acvr1c in memory consolidation. In addition to overall gene expression levels, we identify potential regulators upstream of gene targets within the window for cognitive enhancement. Additionally, we use three complementary analyses to examine the mechanisms responsible for maintaining the ‘molecular memory window’ for exercise utilizing up regulated differentially expressed genes compared to sedentary controls. These analyses include: gene coexpression network analysis to identify potential hub genes for each exercise condition, predicted pathways altered by exercise, and gene ontology enrichment analysis of cellular components altered by exercise. Together, results identify Acvr1c as one of few genes up regulated only under conditions where exercise enabled the formation of long-term memory and synaptic plasticity, suggesting a role for Acvr1c in facilitation of memory consolidation. Follow up experiments manipulating ACVR1C function, find that it serves as an essential bidirectional regulator of long-term memory formation capable of alleviating impairments in hippocampus-dependent memory and synaptic plasticity associated with age and Alzheimer’s Disease.
2022-12-01 | GSE208615 | GEO
Project description:Exercise has been recognized as a beneficial factor for cognitive health, particularly in relation to the hippocampus, a vital brain region responsible for learning and memory. Previous research has demonstrated that exercise-mediated improvement of learning and memory in humans and rodents correlates with increased adult neurogenesis and processes related to enhanced synaptic plasticity. Nevertheless, the underlying molecular mechanisms are not fully understood. With the aim to further elucidate these mechanisms we provide a comprehensive dataset of the mouse hippocampal transcriptome at the single-cell level after four weeks of voluntary wheel-running. Our analysis provides a number of interesting observations. For example, the results suggest that exercise affects adult neurogenesis by accelerating the maturation of a subpopulation of Prdm16-expressing neurons. Moreover, we uncover the existence of an intricate crosstalk among multiple vital signaling pathways such as NF-κB, Wnt/β-catenin, Notch, retinoic acid (RA) pathways altered upon exercise in a specific cluster of excitatory neurons within the Cornu Ammonis (CA) region of the hippocampus. In conclusion, our study provides an important dataset and sheds further light on the molecular changes induced by exercise in the hippocampus. These findings have implications for developing targeted interventions aimed at optimizing cognitive health and preventing age-related cognitive decline.
2023-12-31 | GSE234278 | GEO
Project description:Positive experiences, such as social interaction, cognitive training and physical exercise, have been shown to ameliorate some of the harms to cognition associated with ageing. Animal models of positive interventions, commonly known as environmental enrichment, strongly influence neuronal morphology and synaptic function and enhance cognitive performance. While the profound structural and functional benefits of enrichment have been appreciated for decades, little is known as to how the environment influences neurons to respond and adapt to these positive sensory experiences. We show that adult and aged male wild-type mice that underwent a 10-week environmental enrichment protocol demonstrated improved performance in a variety of behavioural tasks, including those testing spatial working and spatial reference memory, and an enhancement in hippocampal LTP. Aged animals in particular benefitted from enrichment, performing spatial memory tasks at levels similar to healthy adult mice. Many of these benefits, including in gene expression, were absent in mice with a mutation in an enzyme, MSK1, which is activated by BDNF, a growth factor implicated in rodent and human cognition. We conclude that enrichment is beneficial across the lifespan and that MSK1 is required for the full extent of these experience-induced improvements of cognitive abilities, synaptic plasticity and gene expression.
2023-06-20 | GSE235037 | GEO
Project description:Exercise improves brain function enhancing neuronal plasticity and cognitive enhancement. For voluntary resistance wheel running (RWR) exercise, with a load of 30% of body weight, we reported enhancement of neurogenesis and spatial memory associated with hippocampal brain-derived neurotrophic factor (BDNF) signaling compared to wheel running (WR) without a load (Lee et al., 2012; Lee et al., 2013). Despite these new evidences, mechanisms for RWR-induced improvement of hippocampal function remained to be clarified. In the present study, we have utilized the high-throughput DNA microarray approach to gain deep insight into molecular mechanisms underlying these changes that could be novel targets of RWR-induced hippocampal plasticity. To do so, whole genome (4x44K) high-density oligonucleotide microarrays were used to monitor the expression level of gene transcripts in the hippocampus of rats voluntary running for 4 weeks in comparison with sedentary animals. These rats showed a significant decrease in average running distance although average work levels immensely increased 12-fold in the RWR group, resulting in muscular adaptation for the fast-twitch plantaris muscle. DNA microarray analysis revealed that 122 (sedentary x WR) and 157 (sedentary x RWR) genes were up-regulated (> 1.5-fold change) as compared with 97 (sedentary x WR) and 467 (sedentary x RWR) down-regulated genes (< 0.75-fold change). Functional categorization using the Ingenuity Pathway Analysis (IPA) revealed expression pattern changes in the major categories of disease and disorders, molecular functions and physiological system development and function. Among these, RWR up-regulated genes such as NFATc1, AVPR1A and FGFR4, which are crucial role for neuronal development and its functions. The down-regulated inflammatory cytokines (IL1B, IL10, IL2RA, TNF) and chemokines (CXCL1, CXCL9, CXCL10, CCL2, CCL13, CCR4) might be important to neuronal dysfunction and vulnerability. Taken together, these gene candidates are suggested to play a critical role in hippocampal plasticity. This is a first study presenting not only new information into the voluntary RWR influenced transcriptome in the rat hippocampus, but also provides a hypothesis for the RWR influenced enhancement in brain function.
2014-10-09 | GSE52516 | GEO
Project description:P300/CBP and BET inhibition have synergistic effects in NMC. To explore the molecular mechanisms of this synergistic effect, transcriptomic profiling was performed in HCC2429 cells incubated with 250 nM A-485 and 50 nM JQ1 alone or combined.
2020-04-07 | E-MTAB-8955 | biostudies-arrayexpress
Project description:Background: Non-alcoholic steatohepatitis (NASH) has become one of the most common liver diseases and is still without approved pharmacotherapy. Lifestyle interventions using exercise and diet change remain the current treatment of choice and even a small weight loss (5-7%) can already have a beneficial effect on NASH. However#the underlying molecular mechanisms of exercise and diet interventions remain largely elusive#and it is unclear whether they exert their health effects via similar or different pathways. Methods: Ldlr-/-.Leiden mice received a high fat diet (HFD) for 30 weeks to establish an advanced state of NASH/fibrosis with simultaneous atherosclerosis development. Groups of mice were then either left untreated (control group) or were treated for 20 weeks with exercise (running wheel)#diet change (switch to a low fat chow diet) or the combination thereof. The liver and distant organs including heart#white adipose tissue (WAT) and muscle were histologically examined. Comprehensive transcriptome analysis of liver#WAT and muscle revealed the organ-specific effects of exercise and diet and defined the underlying pathways. Results: Exercise and dietary change significantly reduced body weight#fat mass#adipocyte size and improved myosteatosis and muscle function with additive effects of combination treatment. WAT inflammation was significantly improved by diet change#tended to be reduced with exercise#and combination therapy had no additive effect. Hepatic steatosis and inflammation were almost fully reversed by exercise and diet change#while hepatic fibrosis tended to be improved with exercise and was significantly improved with diet change. Additive effects for the combination therapy were shown for liver steatosis and associated liver lipids#and atherosclerosis#but not for hepatic inflammation and fibrosis. Pathway analysis revealed complementary effects on metabolic pathways and lipid handling processes#thereby substantiating the added value of combined lifestyle treatment. Conclusions: Exercise#diet change and the combination thereof can reverse established NASH/fibrosis in obese Ldlr-/-.Leiden mice. In addition#the lifestyle interventions had beneficial effects on atherosclerosis#WAT inflammation and muscle function. For steatosis and other parameters related to adiposity or lipid metabolism#exercise and dietary change affected more distinct pathways that acted complementary when the interventions were combined resulting in an additive effect for the combination therapy on important endpoints including NASH and atherosclerosis. For inflammation#exercise and diet change shared several underlying pathways resulting in a net similar effect when the interventions were combined.
2021-07-10 | GSE179394 | GEO
Project description:TNF is a proinflammatory cytokine with established roles in host defense and immune system organogenesis. Here we report a novel physiological function of TNF that extends its effect beyond the host into the developing offspring. A partial/complete maternal TNF-deficit, specifically in hematopoietic cells, resulted in reduced milk levels of chemokines IP-10, MCP-1/-3/-5, and MIP-1β, which in turn, augmented offspring postnatal hippocampal proliferation, leading to improved adult spatial memory. These effects were reproduced by the postpartum administration of a clinically used anti-TNF agent. Chemokines, fed to suckling pups of TNF-deficient mothers, restored both postnatal proliferation and adult spatial memory to normal levels. This work identifies a TNF-dependent “lactrocrine” pathway that programs offspring hippocampal development and memory. The level of ambient TNF is known to be downregulated by physical activity/exercise and adaptive stress; thus, we propose that the maternal TNF-milk chemokine pathway evolved to promote offspring adaptation to post-weaning environmental challenges/competition. Examined transcriptomes of TNF wild type offspring of TNF wild type or heterozygouse mothers
2013-12-01 | E-GEOD-52069 | biostudies-arrayexpress
Project description:Despite the predominance and high heritability of Attention-Deficit/Hyperactivity Disorder (ADHD), its etiology remains elusive. Preclinical and clinical evidence partly points to impaired limbic system function, particularly that of the hippocampus (HPC). Children diagnosed with ADHD often struggle with deficits in executive function, temporal processing, and visuospatial memory, the defining hallmarks of the predominantly inattentive presentation (ADHD-PI), thought to be subserved by the HPC brain region. However, the specific genes/proteins involved and how they shape the hippocampal makeup to influence ADHD behavior are poorly understood. As an exploratory tool, hippocampal tissues from a mouse model overexpressing thyroid hormone-responsive protein (THRSP), with defining characteristics of ADHD-PI presentation, were utilized for proteomic analyses. Results revealed differential expressions of proteins involved in Wnt signaling. Compared to THRSP knockout (KO), THRSP OE mice have impaired attention and memory concomitant to dysregulated Wnt signaling affecting hippocampal cell proliferation (BrdU) and neurogenic markers expressions (i.e., NEU-N, GFAP), markers of neural stem cell (NSC) activity. Also, exposure to a combination of enriched environment and treadmill exercise improves behavioral deficits in THRSP OE mice and improves Wnt signaling and NSC activity.
2023-01-18 | PXD038525 | Pride