Effect Of Gaba In The Hippocampal Dg Region On Spatial Memory Impairment In Vascular Dementia Rats

Vascular dementia (VD) is a kind of acquired intellectual impairment syndrome caused by brain tissue damage related to cerebral vascular factors, and it mainly manifests dysfunction of memory and cognitive. VD is related to many factors, such as decrease in blood flow, leukoaraiosis, intracellular calcium overload, toxicity of excitatory amino acids, as well as cell apoptosis and delayed neuronal necrosis after ischemia, and so on. The dysfunction of memory and cognitive includes the impairment of spatial learning and memory. Hippocampus is the key structure of controlling learning and memory in mammals, and is especially important in the spatial memory. Studies have shown that abnormality of hippocampus may be an important reason of memory and cognitive disorders in VD patients, however, the concrete relationship between hippocampus and memory disorder, especially the neurochemical mechanism relating with neurotransmitter remains unclear,y-aminobutyric acid (GABA) is an important inhibitory neurotransmitter which extensively distributes in the central nervous system. Several studies indicate that GABA neurons and its receptors exist in the hippocampal dentate gyrus (DG) region, and which are involved in the regulation of learning and memory. Therefore, to investigate the possible involvement of GABA in spatial memory impairment of VD, the VD rat model was prepared by permanent ligation of bilateral common carotid artery, and then the extracellular concentration of GABA in the DG region was measured by microdialysis and high performance liquid chromatography (HPLC) techniques, and the spatial memory ability of the rats was observed by Morris water maze. Next, the antagonist or agonist of GABA receptors was microinjected into the DG region, and then the water maze test was performed.The results of the present study are as follows:(1) The extracellular concentration of GABA in hippocampal DG region were significantly decreased in the VD model rats (P<0.05). (2) Compared with sham-operated group, the VD model rats showed significantly longer escape latency to locate the hidden platform and fewer number of crossing over the previous platform site (P<0.05, respectively).(3) Microinjection of saclofen (an antagonist of GABAB receptor)(200pmol/μL) into the hippocampal DG region significantly shortened the escape latency and increased the number of crossing in VD model rats (P<0.05, respectively), whereas bicuculline (an antagonist of GABAA receptor)(1μg/μl) did not influence them (P>0.05, respectively).(4) In normal rats, microinjection of baclofen (an agonist of GABAB receptor)(1μg/μl) into the DG region prolonged the escape latency and decreased the number of crossing (P<0.05, respectively), however muscimol (1μg/μl), an agonist of GABAA receptor, prolonged the escape latency (P<0.05), but did not affect the number of crossing (P>0.05).Conclusion:1. Spatial memory impairment of VD model rats is related to increase in GAB A concentrations in the hippocampal DG region.2. GABA in the DG region involves in spatial memory impairment of VD model rats by means of activation of GABAB receptor.