Journal Article

Enriched Environment Prevents Hypobaric Hypoxia Induced Memory Impairment and Neurodegeneration: Role of BDNF/PI3K/GSK3β Pathway Coupled with CREB Activation

Jain, Vishal, Ilavazhagan, Govindasamy, Baitharu, Iswar, Prasad, Dipti

2013

Overview

Adverse environmental conditions such as hypobaric hypoxia (HH) cause memory impairment by affecting cellular machinery leading to neurodegeneration. Providing enriched environment (EE) is found to be beneficial for curing several neurodegenerative disorders. The protective role of EE in preventing HH induced neuronal death has been reported previously but the involved mechanism is still not clearly understood. The present study is an attempt to verify the impact of EE on spatial memory during HH and also to explore the possible role of neurotrophin in EE mediated neuroprotection. Signaling mechanism involved in neuroprotection was also explored. Male Sprague Dawley rats were simulated to HH condition in an Animal Decompression Chamber at an altitude of 25000 feet in standard and enriched cages for 7 days. Spatial memory was assessed through Morris Water Maze. Role of different neurotrophins was explored by gene silencing and inhibitors for their respective receptors. Further, using different blockers signaling pathway was also explored. Finding of the present study suggested that EE prevents HH mediated memory impairment and neurodegeneration. Also brain-derived neurotrophic factor (BDNF) plays a major role in EE mediated neuroprotection and it effectively prevented neurodegeneration by activating PI3K/AKT pathway resulting in GSK3β inactivation which further inhibits apoptosis. Moreover GSK3β phosphorylation and hence its inactivation upregulates CREB phosphorylation which may also accounts for activation of survival machinery in cells and provides neuroprotection. From these observations it can be postulated that EE has a therapeutic potential in amelioration of HH induced memory impairment and neurodegeneration. Hence it may be used as a non invasive and non pharmacological intervention against various neurological disorders.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 1-Phosphatidylinositol 3-kinase / Activation / AKT protein / Alzheimer's disease / Alzheimers disease / Animal cognition / Animals / Apoptosis / Behavior, Animal / Biology / Brain / Brain research / Brain-derived neurotrophic factor / Brain-Derived Neurotrophic Factor - metabolism / Cages / Cell Death / Cell survival / Cyclic AMP response element-binding protein / Cyclic AMP Response Element-Binding Protein - metabolism / Deactivation / Decompression / Disorders / Enrichment / Environment / Environmental conditions / Enzyme Activation / Gene expression / Gene Knockdown Techniques / Gene silencing / Glycogen Synthase Kinase 3 - antagonists & inhibitors / Glycogen Synthase Kinase 3 - metabolism / Glycogen Synthase Kinase 3 beta / Housing conditions / Hypoxia / Hypoxia - complications / Hypoxia - enzymology / Hypoxia - pathology / Impairment / Inactivation / Ischemia / Kinases / Machinery and equipment / Male / Maze Learning / Memory / Memory Disorders - enzymology / Memory Disorders - etiology / Memory Disorders - pathology / Memory tasks / Meningitis / Models, Biological / Nerve Degeneration - enzymology / Nerve Degeneration - etiology / Nerve Degeneration - pathology / Nerve Growth Factors - metabolism / Neurobiology / Neurodegeneration / Neurodegenerative diseases / Neurogenesis / Neurological diseases / Neuroprotection / Neuroprotective Agents - metabolism / Neurosciences / Neurotrophic factors / Oxidative stress / Pharmacology / Phosphatidylinositol 3-Kinases - metabolism / Phosphorylation / Physiology / Rats / Rats, Sprague-Dawley / Receptor, trkB - metabolism / Receptors / Rodents / Signal Transduction / Signaling / Spatial analysis / Spatial memory