Journal
JOURNAL OF NEUROCHEMISTRY
Volume 158, Issue 2, Pages 413-428Publisher
WILEY
DOI: 10.1111/jnc.15370
Keywords
AMPA receptor; cognitive deficits; fisetin; schizophrenia; synaptic plasticity
Categories
Funding
- National Natural Science Foundation of China [82060258]
- Jiangxi Provincial Natural Science Foundation [2020BCG74002, 20202BAB206026, 20202BAB216012, 20202BBG73022]
- Natural Science Foundation of Fujian Province of China [2019J01164]
- Scientific Foundation of Quanzhou City for High Level Talents [2019C075R]
Ask authors/readers for more resources
The study shows that fisetin treatment can reverse deficits in hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, indicating fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.
Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of this study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins was measured by western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB), and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available