The Role of SNARE Complex in the Depression-like Behaviour of Prenatal Stress offspring Rats

抄録

Background: It is widely known that prenatal stress (PS) exposure causes depression-like behaviour to offspring, as well as maladaptive responses including neurobiological and physiological changes. Glutamate neurotransmission was recently impaired in the action of PS and in antidepressant mechanisms, but little is understood about the mechanisms underlying this consequence. In the synapse, vesicular docking and neurotransmitter release requires the formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. Impairments in vesicle docking, and alterations in SNARE complex formation are associated with impaired neurotransmitter release.

Methods: To examine the effect of PS on the SNARE complex, pregnant rats were assigned to Control group (CON) and PS group (PS). PS rats were exposed to restraint stress on days 14-20 of pregnancy three times daily for 45min.

Results: Immunoblotting of the hippocampal and prefrontal cortex homogenates revealed significantly increased SNARE complex formation (P<0.05). For the offspring, the SNARE protein SNAP-25, VAMP-2 and syntaxin 1a protein expression were significantly increased in the hippocampus and prefrontal cortex (P<0.05), associated with increased Munc-18, alpha-synuclein, CSP-alpha, complex1 and complex2, which chaperone SNARE-complex formation (P<0.05).

Conclusion: Increased SNARE complex and three SNARE protein of PS may explain the increase of glutamate in synaptic cleft and its downstream excitotoxicity. (Supported by National Natural Science Foundation of China, No: 31600822).