Modulation of Cholinergic Activity in the Hippocampus and Behavioral Alterations Induced by Prenatal Administration of Valproic Acid in Rats
Journal Title: The 1st Annual Meeting of Georgian Center for Neuroscience Research - Year 2020, Vol 2, Issue 20
Abstract
Autism spectrum disorders (ASD) are defined by behavioral deficits in social interaction and communication, repetitive stereotyped behaviors, and restricted interests. The etiology of autism is not known. Neurotransmitters that are most commonly associated with the pathogenesis of ASD are GABAergic, glutamatergic and serotonergic systems. Evidence of relationship between ASD and cholinergic system is still weak. In the human cerebral cortex and hippocampus, measures of cholinergic activity, demonstrate substantial changes during the early postnatal period, when symptoms of autism first become manifest. However, Autism related behavior and spatial memory accompanied by modulation cholinergic activity in the hippocampus has not been studied. In this study, we used valproic acid (VPA) induced animal model of ASD to study the hippocampal cholinergic activity in accordance with autism related behavior and spatial memory. In the present study female outbred white rats received a single intraperitoneal injection of 500 mg/kg sodium VPA on the 12.5 day after conception, and control females were injected with physiological saline at the same time. Behavioral experiments were carried out on male offspring on PNDs 30-35. Sociability was evaluated in a three-chamber apparatus and hippocampal dependent spatial memory was assessed in the Morris water maze (MWM). The number of acetylcholinesterase (AChE) positive cells in the hippocampus was assessed by immunostaining. An immunohistochemical evaluation revealed that the number of AChE positive neurons in the CA1 field of hippocampus of VPA treated rats significantly higher vs. control group, but number of AChE positive neurons in the CA3 field of the hippocampus was not different from the control group. Our study showed marked decreases in social interaction in VPA-treated rats. In the sociability test, VPA rat stayed more time in the empty space than rat in control group and their staying time in the compartment with a conspecific rat was significantly lower than control rat suggesting the deficits in sociability. In MWM testing all rats exhibited a decreased latency to find the hidden platform across the eight training trials. During the probe test which was performed 1 hour or 3 days later after task acquisition trained rats of all groups spent significantly longer than chance in the test quadrant where the hidden platform was located in training trials and did not differ significantly among each other. These results revealed that spatial learning and memory in MWM in VPA treated rat was not affected. The present results for the first time demonstrate that deficit in sociability in early period of development of ASD rat model is paralleled with significant changes in the cholinergic activity in the hippocampus and suggest the potential for treatment of ASD based on cholinergic activity modulation. (Supported by the funding from the SRNSFG: Grant # - FR-18-14029).
Authors and Affiliations
M. Chighladze, M. Dashniani
Keywords
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- EP ID EP677943
- DOI 10.29088/GCNR-2020.34
- Views 186
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