Enriched Environment Altered Aberrant Hippocampal Neurogenesis and Improved Long-Term Consequences After Temporal Lobe Epilepsy in Adult Rats

Abstract

Abnormal hippocampal neurogenesis is thought to contribute to cognitive impairments in chronic temporal lobe epilepsy (TLE). Stromal cell-derived factor-1 (SDF-1) and its specific receptor CXCR4 play important roles in neurogenesis. We investigated whether enriched environment (EE) might be beneficial for TLE. Adult rats were randomly assigned as control rats, rats subjected to status epilepticus (SE), or post-SE rats treated with EE for 30 days. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze. Western blot was used to measure the expression of SDF-1 and CXCR4 in the hippocampus. In the present study, we found the TLE model resulted in aberrant neurogenesis such as reduced proliferation, intensified dendritic development of newborn neurons, as well as spontaneous seizures and cognitive impairments. More importantly, EE treatment significantly increased the cell proliferation and survival, extended the apical dendrites, and delayed the attenuation of the expression of SDF-1 and CXCR4, accompanied by decreased long-term seizure activity and improved cognitive impairments in adult rats after TLE. These results provided morphological evidence that EE might be beneficial for treating TLE.

Increased protein expression levels of pCREB, BDNF and SDF-1/CXCR4 in the hippocampus may be associated with enhanced neurogenesis induced by environmental enrichment

“…Morris water maze test. Spatial learning was analyzed with a match-to-place version of the Morris water maze test on days 31-33, as described previously (23). Following the assessment (day 33), a probe trial of 60 sec in the absence of the platform was performed to estimate the ability of the rats to recall the location of the platform by measuring the number of passings over its previous location.…”

<p>The Clinical Effect of Electroconvulsive Therapy and Its Relationship with Serum Levels of MMP-9 and CXCL12 in Patients with Mania</p>

“…CXCL12 and its cognitive receptor CXCR4 are expressed by neural stem cells are involved in adult neurogenesis. 32 Enhanced environment induces neuronal plasticity and hippocampal neurogenesis which is accompanied by was accompanied by the increased expressions of SDF-1 and CXCR4 in the hippocampus, 33 indicating that CXCL12 is a neurogenesis inducer factor. This notion was supported by another observation which demonstrated that CXCR4 antagonist, AMD3100 reversed the effect of EE on neurogenesis.…”

Exposure to enriched environment restores altered passive avoidance learning and ameliorates hippocampal injury in male albino Wistar rats subjected to chronic restraint stress

“…Zhang et al . [ 27 ] reported the beneficial effects of using EE in rats having temporal lobe epilepsy. Their study revealed enhanced hippocampal neurogenesis, improved cognitive impairments, and decreased long-term seizure activity in epileptic rats after exposure to EE.…”