Interaction of serotonin transporter and TGFB1 facilitates histone serotonylation-mediated synaptic plasticity following environmental enrichment in stressed mouse Mus booduga.

Environmental Novelty Activates β2-Adrenergic Signaling to Prevent the Impairment of Hippocampal LTP by Aβ Oligomers

Enriching the environment to disinhibit the brain and improve cognition

P4-322: Complete environmental enrichment is required to protect AD transgenic mice against cognitive impairment, reduce a-beta deposition, and increase synaptophysin staining: Involvement of both amyloid-dependent and independent mechanisms

Environmental enrichment (EE) has an influential role in reducing behavioral reactivity to stress. We previously observed that EE reduces the anxiety-like behavior in the field mouse Mus booduga accompanied by a reduction in the expression of molecules involved in the stress pathway. In this study, we demonstrate the effect of different housing condition on regulation of micro-RNA-183-SC35-mediated splicing of acetylcholinesterase (AChE). Adult male M. booduga were captured from an agricultural field and housed under nonenriched standard conditions (SC) for 7 days and considered as directly from the wild (DW). On day 8, individuals were randomly assigned to three groups; DW, SC, and EE. The DW group's anxiety-like behavior was assessed in the elevated plus maze (EPM) and open field test (OFT). The SC and EE groups were transferred to their respective conditions and housed for another 30 days. The mice housed in EE showed less anxiety-like behavior on EPM and in OFT compared with DW and SC mice. Interestingly, miR-183 expression was increased following exposure to EPM in EE mice but not in SC mice. Subsequently, the upregulated miR-183 expression suppresses the SC35 expression and shifting of splicing from AChE-S (synaptic) to AChE-R (read-through) form, whereas standard housing condition downregulate miR-183 and induces the splicing of AChE. The upregulated AChE-R form possibly terminates ACh transmission, which is reflected in the level of anxiety-like behavior. Overall, the present study suggests that EE effectively regulates the miR-183 pathway to reduce anxiety-like behavior.

Environmental enrichment exerts anxiolytic effects in the Indian field mouse ( Mus booduga)

Long-term environmental enrichment (EE) elicits enduring effects on the adult brain, including altered synaptic plasticity. Synaptic plasticity may underlie memory formation and includes robust (>24 h) and weak (<2 h) forms of long-term potentiation (LTP) and long-term depression (LTD). Most studies of the effect of EE on synaptic efficacy have examined the consequences of very prolonged EE-exposure. It is unclear whether brief exposure to EE can alter synaptic plasticity. Clarifying this issue could help develop strategies to address cognitive deficits arising from neglect in children or adults. We assessed whether short-term EE elicits alterations in hippocampal synaptic plasticity and if social context may play a role. Adult mice were exposed to EE for 14 consecutive days. We found that robust late-LTP (>24 h) and short-term depression (<2 h) at Schaffer-collateral-CA1 synapses in freely behaving mice were unaltered, whereas early-LTP (E-LTP, <2 h) was significantly enhanced by EE. Effects were transient: E-LTP returned to control levels 1 week after cessation of EE. Six weeks later, animals were re-exposed to EE for 14 days. Under these conditions, E-LTP was facilitated into L-LTP (>24 h), suggesting that metaplasticity was induced during the first EE experience and that EE-mediated modifications are cumulative. Effects were absent in mice that underwent solitary enrichment or were group-housed without EE. These data suggest that EE in naïve animals strengthens E-LTP, and also promotes L-LTP in animals that underwent EE in the past. This indicates that brief exposure to EE, particularly under social conditions can elicit lasting positive effects on synaptic strength that may have beneficial consequences for cognition that depends on synaptic plasticity.

Environmental enrichment (EE) through combination of social and non-biological stimuli enhances activity-dependent synaptic plasticity and improves behavioural performance. Our earlier studies have suggested that EE resilience the stress induced depression/ anxiety-like behaviour in Indian field mice Mus booduga. This study was designed to test whether EE reverses the social isolation (SI) induced effect and improve memory. Field-caught mice M. booduga were subjected to behaviour test (Direct wild, DW), remaining animals were housed under SI for ten days and then housed for short-term at standard condition (STSC)/ long-term at standard condition (LTSC) or as group in EE cage. Subsequently, we have examined reference, working memory and expression of genes associated with synaptic plasticity. Our analysis have shown that EE reversed SI induced impairment in reference, working memory and other accompanied changes i.e. increased level of Intersectin 1 (ITSN1), Huntingtin (Htt), Synaptotagmin -IV (SYT4), variants of brain-derived neurotrophic factor (Bdnf - III), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluR1) expression, and decreased variants of Bdnf (IV), BDNF, Reelin, Apolipoprotein E receptor 2 (ApoER2), very low-density lipoprotein receptor (VLDLR), Src family tyrosine kinase (SFKs), Disabled protein (Dab)-1, Protein kinase B (PKB/Akt), GluR2, Mitogen-activated protein kinase (MAPK) and Extracellular signal-regulated kinase (ERK1/2) expression. In addition, SI induced reduction in BDNF expressing neurons in dentate gyrus of hippocampus reversed by EE. Further, we found that SI decreases small neuro-active molecules such as Benzenedicarboxylic acid, and increases 2-Pregnene in the hippocampus and feces reversed by EE. Overall, this study demonstrated that EE is effectively reversed the SI induced memory impairment by potentially regulating the molecules associated with the ITSN1-Reelin–AMPA receptor pathway to increase synaptic plasticity.

Environmental enrichment (EE) through combination of social and non-biological stimuli enhances activity-dependent synaptic plasticity and improves behavioural performance. Our earlier studies have suggested that EE resilience the stress induced depression/ anxiety-like behaviour in Indian field mice Mus booduga. This study was designed to test whether EE reverses the social isolation (SI) induced effect and improve memory. Field-caught mice M. booduga were subjected to behaviour test (Direct wild, DW), remaining animals were housed under SI for ten days and then housed for short-term at standard condition (STSC)/ long-term at standard condition (LTSC) or as group in EE cage. Subsequently, we have examined reference, working memory and expression of genes associated with synaptic plasticity. Our analysis have shown that EE reversed SI induced impairment in reference, working memory and other accompanied changes i.e. increased level of Intersectin 1 (ITSN1), Huntingtin (Htt), Synaptotagmin -IV (SYT4), variants of brain-derived neurotrophic factor (Bdnf - III), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (GluR1) expression, and decreased variants of Bdnf (IV), BDNF, Reelin, Apolipoprotein E receptor 2 (ApoER2), very low-density lipoprotein receptor (VLDLR), Src family tyrosine kinase (SFKs), Disabled protein (Dab)-1, Protein kinase B (PKB/Akt), GluR2, Mitogen-activated protein kinase (MAPK) and Extracellular signal-regulated kinase (ERK1/2) expression. In addition, SI induced reduction in BDNF expressing neurons in dentate gyrus of hippocampus reversed by EE. Further, we found that SI decreases small neuro-active molecules such as Benzenedicarboxylic acid, and increases 2-Pregnene in the hippocampus and feces reversed by EE. Overall, this study demonstrated that EE is effectively reversed the SI induced memory impairment by potentially regulating the molecules associated with the ITSN1-Reelin-AMPA receptor pathway to increase synaptic plasticity.

We have previously reported that inhibition of the serotonin transporter (SERT) by selective serotonin reuptake inhibitor (SSRI) fluoxetine significantly reduces the number of tryptophan hydroxylase (TPH)-positive cells in the dorsal raphe nucleus (DRN). We have been interested in exploring whether this SSRI-induced change in TPH might be modified by housing in an enriched environment. Like SSRI antidepressants, environmental enrichment (EE) and physical exercise have been found to have efficacy in the prevention and alleviation of depression. We postulated that EE with exercise and SERT inhibition would similarly affect TPH regulation and that EE with exercise might modify the effect of fluoxetine on TPH. Three week old male Sprague-Dawley rats were housed in either a standard cage (SE) or an enriched environment (EE). SE animals were singly housed with no access to enrichment objects. EE animals were group housed and were provided with various enrichment objects (e.g. running wheel) that were changed and rearranged regularly. Nine weeks after the experiment began, the rats were randomly assigned to one of four treatment groups: (1) SE control; (2) SE fluoxetine; (3) EE control; or (4) EE fluoxetine. Fluoxetine (5 mg/kg/day) was placed in the drinking water. Sections of DRN were processed for TPH immunohistochemistry. The number of TPH-positive cells was determined by blinded, manual counting. Results were analyzed by analysis of variance (ANOVA) followed by post-hoc Tukey tests. Significance was set at P < 0.05. For animals housed in a standard environment, fluoxetine induced a significant 29% reduction in the number of TPH-immunoreactive cells in the DRN. A similar reduction in TPH immunoreactivity was observed in animals that were housed in an enriched environment but not exposed to fluoxetine (39%). The number of TPH-positive cells in the DRN for animals housed in an enriched environment and exposed to fluoxetine was not significantly different than animals housed in an enriched environment and not exposed to fluoxetine. The reduction of TPH immunoreactivity in the DRN by EE with exercise suggests that a modified housing environment and voluntary exercise affects regulation of TPH, possibly via a mechanism similar to that of SERT inhibitors. This downregulation of serotonin biosynthesis by fluoxetine and EE with exercise may ultimately play a role in the therapeutic action of both interventions.

Enriched environment ameliorates neurobehavioral abnormalities, hippocampal inflammation, and synaptic dysfunction in adult male mice exposed to intermittent hypoxia during pregnancy.

Environmental enrichment (EE) has been shown in old rats to improve learning and memory. Vitamin D (VitD) has also been shown to modulate age-related, cognitive dysfunction. As both EE and VitD could work to improve cognition via enhancement of neurotrophic factors, their effects might occlude one another. Therefore, a clinically relevant question is whether noted cognition-promoting effects of EE and VitD can co-occur. Aged rats were housed for 6weeks in one of three housing conditions: environmentally enriched (EE), socially enriched (SE), or standard condition (SC). Further, a 4th group was co-treated with VitDsupplementation (400IUkg-1 daily, 6weeks)under EE conditions (EE + VitD). Treatment with VitD and EE housingwere associated with higher score on measures of learning and memory and exhibited lower anxiety scores compared to EE alone, SE or SC as assayed in the elevated plus maze, Morris water maze, passive avoidance, and open field tasks. Additionally, inthe EE + VitD group, mRNA expression levels of NGF, TrkA, BDNF, Nrf2, and IGF-1 were significantly higher compared to expression seen in the EE group. Furthermore, field potential recordings showed that EE + VitD resulted in a greater enhancement of hippocampal LTP and neuronal excitability when compared to EE alone. These findings demonstrate that in aged rats exposure to EE and VitD results in effects on hippocampal cognitive dysfunction and molecular mechanisms which are greater than effects of EE alone, suggesting potential for synergistic therapeutic effects for management of age-related cognitive decline.

P.2.017 Size does matter: environmental enrichment rescues cognitive and synaptic deficits following olfactory bulbectomy in mice

Sensory, motor, and cognitive stimuli, resulting from interactions with the environment, play a key role in optimizing and modifying the neuronal circuitry required for normal brain function. An experimental animal model for this phenomenon comprises environmental enrichment (EE) in rodents. EE causes profound changes in neuronal and signaling levels of excitation and plasticity throughout the entire central nervous system and the hippocampus is particularly affected. The mechanisms underlying these changes are not yet fully understood. As brain-derived neurotrophic factor (BDNF) supports hippocampal long-term potentiation (LTP), we explored whether it participates in the facilitation of synaptic plasticity and hippocampus-dependent learning that occurs following EE. In the absence of EE, LTP elicited by high-frequency stimulation was equivalent in wildtype mice and heterozygous BDNF(+/-) siblings. LTP elicited by theta-burst stimulation in BDNF(+/-) mice was less than in wildtypes. Long-term depression (LTD) was also impaired. EE for three weeks, beginning after weaning, improved hippocampal LTP in both wildtype and transgenic animals, with LTP in transgenics achieving levels seen in wildtypes in the absence of EE. Object recognition memory was evident in wildtypes 24 h and 7 days after initial object exposure. EE improved memory performance in wildtypes 24 h but not 7 days after initial exposure. BDNF(+/-) mice in the absence of EE showed impaired memory 7 days after initial object exposure that was restored by EE. Western blotting revealed increased levels of BDNF, but not proBDNF, among both EE cohorts. These data support that BDNF plays an intrinsic role in improvements of synaptic plasticity and cognition that occur in EE.

Event Abstract Back to Event Proteome profiling of hippocampus during chronic hypobaric hypoxia exposure: Enriched environment as a therapeutic approach Vishal Jain1*, Shashi B. Singh1 and Govindasamy Ilavazhagan2 1 Defence Institute of Physiology and Allied Sciences, Department of Neurophysiology, India 2 Hindustan University, Research, India Hypobaric hypoxia (HH) is known to cause cognitive dysfunctions owing to the high oxygen dependency of the brain. Cognitive and motor deficits have been reported to occur on chronic exposure to HH. On the other hand enriched environment (EE) enhances learning and memory, reduces memory decline during different neurological disorders. Previously we have shown that enriched environment improves cognition and decreases neurodegeneration during chronic exposure to hypobaric hypoxia. Present study is designed to explore the effect of enriched environment on hypobaric hypoxia induced alteration in synaptic plasticity and strength. Sprague dawley rats (3 months old) were exposed to hypobaric hypoxia condition in an animal decompression chamber at an altitude of 25000 feet for continuous 7 days. Animals from control group were kept in standard cage whereas enriched group were kept in EE cage. Following exposure rats were sacrificed and hippocampi was dissected out and processed for different experimental protocols. MALDI following 2D electrophoresis was performed to study the global change in hippocampal protein expression. Further expression of different synaptic proteins was assessed through western blotting and immunohistochemistry. Golgi stain was performed to study dendritic arbrorization. Results of the present study showed that identified proteins belong to a diverse variety of functional classes including cell death, proteins involved in oxidative stress metabolism, synaptic proteins, growth factors and proteins associated with signalling. Hypobaric hypoxia decreases expression of synaptic proteins i.e. synaptophysin, PSD-95, synaptotagmin which further validated by western blotting whereas exposing them in enriched environment ameliorate this synaptic loss. Golgi staining reveals increased dendritic arborization, spine density and morphology on exposure to EE during HH. Present study also reveals the possible role of BDNF/TrkB signalling in enriched environment mediated modulation hippocampal synaptic plasticity. Therefore it can be concluded that enriched environment ameliorate HH induced synaptic loss through BDNF/TrkB signalling. Keywords: Synaptophysin, hypoxia, PSD-95, synaptotagmin, BDNF/TrkB signalling Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: YIC02: Young Investigator Colloquium 2 Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Jain V, Singh SB and Ilavazhagan G (2016). Proteome profiling of hippocampus during chronic hypobaric hypoxia exposure: Enriched environment as a therapeutic approach. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00059 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Vishal Jain, Defence Institute of Physiology and Allied Sciences, Department of Neurophysiology, Delhi, Delhi, India, vishal6784@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Vishal Jain Shashi B Singh Govindasamy Ilavazhagan Google Vishal Jain Shashi B Singh Govindasamy Ilavazhagan Google Scholar Vishal Jain Shashi B Singh Govindasamy Ilavazhagan PubMed Vishal Jain Shashi B Singh Govindasamy Ilavazhagan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Extensive enriched environments protect old rats from the aging dependent impairment of spatial cognition, synaptic plasticity and nitric oxide production