ABSTRACT
BACKGROUND AND PURPOSE: As the only ionotropic receptor in the 5-HT receptor family, the 5-HT3 receptor (5-HT3 R) is involved in psychiatric disorders and its modulators have potential therapeutic effects for cognitive impairment in these disorders. However, it remains unclear how 5-HT3 Rs shape synaptic plasticity for memory function. EXPERIMENTAL APPROACH: Extracellular as well as whole-cell electrophysiological recordings were used to monitor hippocampal LTP and synaptic transmission in hippocampal slices in 5-HT3 AR knockout or 5-HT3 AR-GFP mice. Immunocytochemistry, qRT-PCR and western blotting were used to measure receptor expression. We also assessed hippocampal dependent cognition and memory, using the Morris water maze (MWM) and novel object recognition. KEY RESULTS: We found that 5-HT3 R dysfunction impaired hippocampal LTP in Schaffer collateral (SC)-CA1 pathway in hippocampal slices, by facilitating GABAergic inputs in pyramidal cells. This effect was dependent on 5-HT3 Rs on axon terminals. It resulted from reduced expression and function of the cannabinoid receptor 1 (CB1 R) co-localized with 5-HT3 Rs on axon terminals, and then led to diminishment of tonic inhibition of GABA release by CB1 Rs. Inhibition of CB1 Rs mimicked the facilitation of GABAergic transmission by 5-HT3 R disruption. Consequently, mice with hippocampal 5-HT3 R disruption exhibited impaired spatial memory in MWM tasks. CONCLUSION AND IMPLICATIONS: These results suggest that 5-HT3 Rs are crucial in enabling hippocampal synaptic plasticity via a novel CB1 R-GABAA -dependent pathway to regulate spatial memory.
Subject(s)
Long-Term Potentiation , Spatial Memory , Animals , CA1 Region, Hippocampal/metabolism , Hippocampus/metabolism , Humans , Long-Term Potentiation/physiology , Memory Disorders/metabolism , Mice , Receptor, Cannabinoid, CB1/genetics , Receptor, Cannabinoid, CB1/metabolism , Receptors, GABA-A/metabolism , Serotonin/metabolism , gamma-Aminobutyric Acid/metabolismABSTRACT
OBJECTIVE: It was to explore the application of the hepatitis B virus large proteins (HBV-LP) in public health physical examination through clinical testing of HBV-LP in Catering practitioners, students and soldiers of New requisition etc. METHODS: 709 samples of HBV infection people were collected in public health physical examination and all collected samples were detected. ELISA was used to detect HBV serum markers (HBV-M) and HBV-LP. Real-time PCR was applied to detect quantity of HBV DNA. RESULTS: (1) The detectable results of HBV-LP and HBV DNA were no statistical significance in 709 samples. (2) The detectable results of HBV-LP and HBV DNA were also no statistical significance in different models of HBV infection patients. The values of chi2 and P were respectively 2.67, 0.60, 0.00 and 0.10, 0.44, 1.00. S/A of HBV-LP and the copies of HBV-DNA had a positive relationship (r = 0.959, P < 0.05). CONCLUSION: HBV-LP could reflect the level of hepatitis B virus replication and be used to judge the level of hepatitis B virus replication in people of public health physical examination. HBV-LP may be worth using widely in physical examination.
