Effect of the BDNF-TrkB Signalling Pathway on the Synaptic Plasticity of Hippocampal Neurons in Epileptic Rats

Abstract

Background: Epilepsy is a neurological disorder attributed to transient and recurrent abnormal central nervous system (CNS) function due to the abnormal discharge of brain neurons. While many causes have already been recognized, some cannot be identified. Brain-derived neurotrophic factor (BDNF) plays a significant role in regulating the nervous system. The hippocampus, an area prone to epilepsy, has the greatest amounts of BDNF and its receptors expression. Therefore, we used BDNF-tyrosine kinase receptor B (TrkB) signalling as the entry point to study the changes in the synaptic plasticity of hippocampal neurons in rats with kainic acid (KA)-induced epilepsy. Methods: Thirty healthy Specific Pathogen Free (SPF) Sprague Dawley (SD) rats were used to establish an epilepsy model by injecting KA into the lateral ventricle. The KA-only group of rats represented a model, while the KA+K252A group rats were treated with a specific blocker (K252A; 1 μL, 1 mM). Nissl staining was used to observe hippocampal tissue of all rats. Western blotting, immunohistochemical staining, and transmission electron microscopy (TEM) were applied to investigate the hippocampus and explore the potential relationship between BDNF-TrkB expression and the levels of the synaptic plasticity-associated proteins, microtubule-associated protein 2 (MAP-2), synaptophysin (SYP), and postsynaptic density-95 (PSD-95). Results: Histological observations of brain tissue sections and TEM showed that the CA3 region was damaged in KA-injected rats, demonstrating a substantial reduction in the numbers of pyramidal cells and dentate gyrus neurons. The KA-injected groups showed a significantly smaller number of synapses than the normal controls, with some association between BDNF-TrkB and synaptic plasticity observed. The BDNF-TrkB signalling pathway was blocked using the TrkB-specific blocker K252A. Subsequent examination confirmed its relationship with synaptic plasticity-related proteins. The synaptic plasticity-related proteins SYP, PSD-95, and MAP-2 were all decreased, and the decrease in MAP-2 expression was particularly significant. Conclusions: The BDNF-TrkB signaling pathway regulates synaptic plasticity in the hippocampus of epileptic rats by modulating the expression of synaptic proteins such as SYP, PSD-95, and MAP-2. In particular, MAP-2 appears to be strongly implicated, highlighting its potential as a novel therapeutic target for temporal lobe epilepsy.