Entacapone Treatment Modulates Hippocampal Proteins Related to Synaptic Vehicle Trafficking

Abstract

Entacapone, a reversible inhibitor of catechol-O-methyl transferase, is used for patients in Parkinson’s disease because it increases the bioavailability and effectiveness of levodopa. In the present study, we observed that entacapone increases novel object recognition and neuroblasts in the hippocampus. In the present study, two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were performed to compare the abundance profiles of proteins expressed in the hippocampus after entacapone treatment in mice. Results of 2-DE, MALDI-TOF mass spectrometry, and subsequent proteomic analysis revealed an altered protein expression profile in the hippocampus after entacapone treatment. Based on proteomic analysis, 556 spots were paired during the image analysis of 2-DE gels and 76 proteins were significantly changed more than two-fold among identified proteins. Proteomic analysis indicated that treatment with entacapone induced expressional changes in proteins involved in synaptic transmission, cellular processes, cellular signaling, the regulation of cytoskeletal structure, energy metabolism, and various subcellular enzymatic reactions. In particular, entacapone significantly increased proteins related to synaptic trafficking and plasticity, such as dynamin 1, synapsin I, and Munc18-1. Immunohistochemical staining showed the localization of the proteins, and western blot confirmed the significant increases in dynamin I (203.5% of control) in the hippocampus as well as synapsin I (254.0% of control) and Munc18-1 (167.1% of control) in the synaptic vesicle fraction of hippocampus after entacapone treatment. These results suggest that entacapone can enhance hippocampal synaptic trafficking and plasticity against various neurological diseases related to hippocampal dysfunction.

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

“…185 In addition, entacapone enhances hippocampal synaptic plasticity by increasing the expression of hippocampal proteins dynamin I and synapsin I which control synaptic plasticity via BDNF-TrkB. 186 Besides, tolcapone improves the activity of dopaminergic neurons in the cerebral cortex thereby augments cerebral neurological conductivity. 187 Giakoumaki et al 188 revealed that tolcapone enhances working memory and psychomotor performance in animal model through modulation the BDNF expression.…”

“…Findings from a preclinical study observed that entacapone improves hippocampal neurogenesis through activation of the BDNF–TrkB‐pCREB pathway in mice 185 . In addition, entacapone enhances hippocampal synaptic plasticity by increasing the expression of hippocampal proteins dynamin I and synapsin I which control synaptic plasticity via BDNF–TrkB 186 . Besides, tolcapone improves the activity of dopaminergic neurons in the cerebral cortex thereby augments cerebral neurological conductivity 187 .…”