Mar 26, 2014

Small-molecule TrkB agonist 7,8-dihydroxyflavone reverses cognitive and synaptic plasticity deficits in a rat model of schizophrenia

Pharmacology, Biochemistry, and Behavior
Yuan-Jian YangBin Hu

Abstract

Cognitive deficits are the core symptoms of schizophrenia and major contributors to disability in schizophrenic patients, but effective treatments are still lacking. Previous studies have demonstrated that impaired BDNF/TrkB signaling is associated with the cognitive impairments of schizophrenia. 7,8-Dihydroxyflavone (7,8-DHF) has recently been identified as a specific TrkB agonist that crosses the blood-brain barrier after oral or intraperitoneal administration. The present study aimed to assess the effect of 7,8-DHF on the cognitive and synaptic impairments of schizophrenia. A brief disruption of NMDA receptors with MK-801 during early development serves as an animal model for cognitive deficits of schizophrenia. We found that MK-801-treated rats showed significant deficits in working learning ability and hippocampal synaptic plasticity, as well as reduction of BDNF, TrkB, and phosphorylated TrkB in the hippocampus. After intraperitoneal administration with 7,8-DHF (5 mg/kg) once daily for a consecutive 14days, we found that chronic 7,8-DHF treatment significantly enhanced the activation of phosphorylated TrkB at the Y515 and Y816 sites, increased the phosphorylation levels of TrkB downstream signal cascades including ERK1/2,...Continue Reading

Mentioned in this Paper

Neuro-Oncological Ventral Antigen 2
Buffers
Neurotrophic Tyrosine Kinase Receptor Type 2
Congenital Structural Myopathy
Biochemical Pathway
Cyclic AMP-Responsive DNA-Binding Protein
Blood - Brain Barrier Anatomy
Exertion
Tissue Membrane
Dimethyl Sulfoxide

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