Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression.

OBJECTIVE: The study aimed to determine the effect of electroacupuncture (EA) on Wistar Kyoto (WKY) depressive model rats and explore the possible mechanism of EA on hippocampal CA1 region neuronal synaptic plasticity. METHODS: The male WKY rats were randomized to three experimental groups (EA, Sham EA, and Model group, n = 8/group), and Wistar rats as the normal control group (n = 8). EA treatment was administered once daily for 3 weeks at acupuncture points Baihui (GV20) and Yintang (EX-HN3). In the Sham EA group, acupuncture needles were inserted superficially into the acupoints without electrical stimulation. On day 21, the forced swimming test (FST), open field test (OFT) and sucrose preference test (SPT) were conducted. After the behavioral tests, long-term potentiation (LTP) was evoked at Schaffer collateral-CA1 synapses in hippocampal slices in vitro by electrophysiological recording, 5-HTT, 5-HT1A and 5-HT1 B protein levels in the hippocampus CA1 region were examined by using Western blot. RESULT: EA significantly decreased immobility in FST and improved sucrose intake compared with the Sham EA and Model groups. The center time and total move time in OFT were significantly increased in the EA group compared to the Model group. Compared with those of the Sham EA and Model groups, the fEPSP slope of the EA group increased significantly, and the LTP induction was successful. EA significantly decreased 5-HTT protein expression in the hippocampus CA1 region in comparison to the Sham EA and Model groups. Additionally, EA down regulated the 5-HT1A protein expression in the hippocampus CA1 region in comparison to the Sham EA group. CONCLUSION: EA could ameliorate depressive-like behaviors by restoring hippocampus CA1 synaptic plasticity, which might be mainly mediated by regulating 5-HT receptor levels.

Possible antidepressant effects and mechanism of electroacupuncture in behaviors and hippocampal synaptic plasticity in a depression rat model.

Increasing evidences show that hippocampal synaptic plasticity plays a crucial role in the pathogenesis of depression. The objective of this study was to determine whether electroacupuncture (EA) in the Wistar Kyoto (WKY) rat model of depression would exert antidepressant effects and whether this effect would be associated with changes in hippocampal synaptic plasticity. Male WKY rats were randomly divided into three groups (EA, sham EA, and blank control); Wister rats were used as normal control group. Treatment with EA was performed at Baihui (GV20) and Yintang (EX-HN3) once daily for 3 weeks. Forced swimming test (FST), open field test (OFT), and Morris water maze (MWM) were evaluated after 21-day intervention. Long-term potentiation (LTP) was evoked at Schaffer collateral-CA1 synapses in hippocampal slices in vitro. EA treatment significantly reduced immobility time in FST. MWM test showed a significant downward trend in escape latency time from the second to fifth days of experiment, and a higher frequency of crossing the missing quadrant platform in normal control and EA vs other groups. Impaired LTP was detected in Schaffer collateral-CA1 synapses in blank control and sham EA groups. In the western blot, the expression of GluN2B showed significant increase in EA vs sham EA and blank control groups. EA was able to improve depression-like behaviors and reverse the impairment of LTP, which were likely mediated by GluN2B in the hippocampus.

Forebrain NR2B overexpression enhancing fear acquisition and long-term potentiation in the lateral amygdala.

N-methyl-d-aspartic acid (NMDA) receptor-dependent long-term potentiation (LTP) at the thalamus-lateral amygdala (T-LA) synapses is the basis for acquisition of auditory fear memory. However, the role of the NMDA receptor NR2B subunit in synaptic plasticity at T-LA synapses remains speculative. In the present study, using transgenic mice with forebrain-specific overexpression of the NR2B subunit, we have observed that forebrain NR2B overexpression results in enhanced LTP but does not alter long-term depression (LTD) at the T-LA synapses in transgenic mice. To elucidate the cellular mechanisms underlying enhanced LTP at T-LA synapses in these transgenic mice, AMPA and NMDA receptor-mediated postsynaptic currents have been measured. The data show a marked increasing in the amplitude and decay time of NMDA receptor-mediated currents in these transgenic mice. Consistent with enhanced LTP at T-LA synapses, NR2B-transgenic mice exhibit better performance in the acquisition of auditory fear memory than wild-type littermates. Our results demonstrate that up-regulation of NR2B expression facilitates acquisition of auditory cued fear memory and enhances LTP at T-LA synapses.