Aquaporin 4 knockout increases the vulnerability of mice to acute stress and induce depression-like behaviorObjective: Acute stress is related to the deficit of synap" />
The Effect and Underlying Mechanism of Aquaporin 4 Knock-out on Acute Stress of Mice
|School||Huazhong University of Science and Technology|
|Keywords||Aquaporin 4 Depression-like behavior Acute stress Patch clamp EPSC Presynaptic Aquaporin 4|
PartⅠAquaporin 4' dissertation">Aquaporin 4 knockout increases the vulnerability of mice to acute stress and induce depression-like behaviorObjective: Acute stress is related to the deficit of synaptic transmission. Aquaporin 4, the predominant expression of aquaporin protein in astrocyte in CNS (central nervous system), potentially regulated neurotransmission by affecting extracellular neurotransmitter uptake and extracellular K+ buffering. In this study, the effect of aquaporin 4 on the acute stress was investigated by several behavioral experiments.Methods: Forced swim test (FST) and elevated platform test (EPT) were used to study the behavior of mice during acute stress. Meanwhile, ELISA was used to detect the variation of plasma corticosterone before and after acute stress.Results: The immobility time in FST occurred earlier and longer in AQP4 knockout mice than that of wildtype (WT) mice. In EPT, it was shown a remarkable decrease in freezing in AQP4 knockout mice compared with WT mice.Conclusion: AQP4 knockout increases the vulnerability to acute stress and induces depression-like behavior of mice. PARTⅡThe changes in neurotransmission induced by aquaporin 4 knockout in mPFC mediates the acute stress disorder of miceObjective: The behavior change in acute stress may be related to abnormal neurotransmission. In this study, we investigated the synaptic transmission of pyramidal neurons in mPFC (medial prefrontal cortex) by whole-cell patch-clamp recording in brain slice of mice.Methods: Current clamp was used to record the spontaneous action potential of mPFC pyramidal neurons. The mEPSC (miniature excitatory post-synaptic current) and mIPSC (miniature inhibitory post-synaptic current) was recorded by voltage clamp. The evoked EPSC (excitatory post-synaptic current), pre-synaptic plasticity, pre-synaptic release pool size and pre-synaptic release pool recovery time were assessed by paired-recording of mPFC pyramidal pre-synaptic and post-synaptic neurons. Lateral ventricle micro-administration was selected to deliver DHK (GLT-1 inhibitor) into lateral ventricle of WT mice. Then, the mice were conducted FST and EPT.Results: No differences were observed in WT and AQP4 KO mice both on spontaneous action potential and spontaneous miniature post-synaptic current. However, after acute stress, the absence of AQP4 resulted in the increase in the amplitude of mEPSC and decrease in the amplitude and frequency of mIPSC when compared with wide type mice after stress. Besides, AQP4 knockout prolonged the decay time of EPSC and impaired the pre-synaptic plasticity, and also delayed the recovery of presynaptic release pool. Finally, after injection of DHK into lateral ventricle, the WT mice displayed similar behavior as AQP4 knockout mice in EPT and FST. Conclusion: AQP4 knockout does not influence the spontaneous activity of pyramidal neurons in mPFC, but delays the clearance of glutamate in synaptic cleft after acute stress, which results imbalance of excitatory and inhibitory homeostatic and leads to depression-like behavior in EPT and FST.