Changes in the expression of prefoldin subunit 5 depending on synaptic plasticity in the mouse hippocampus.

Abstract

Prefoldin is a molecular chaperone that assists the folding of newly synthesized polypeptide chains and prevents aggregation of misfolded proteins. Dysfunction of prefoldin is one of the causes of neurodegenerative diseases such as Alzheimer's disease. The aim of this study was to clarify the involvement of prefoldin subunit 5 (PFDN5) in synaptic plasticity. PFDN5 protein expressed in the hippocampus was predominantly localized in the pyramidal cell layer of CA1-CA3 regions. Nicotine application caused a long-term potentiation (LTP)-like facilitation in vivo, that is synaptic plasticity, in the mouse hippocampus. The levels of PFDN5 mRNA and protein were increased 2-24 h and 4-24 h, respectively, after intraperitoneal application of nicotine (3 mg/kg, i.p.), finally returning to the basal level. This increase of PFDN5 protein was significantly inhibited by mecamylamine (0.5 mg/kg, i.p.), a non-selective nicotinic acetylcholine receptors (nAChRs) antagonist, and required combined application of ABT-418 (10 mg/kg, i.p.), a selective α4β2 nAChR agonist, and choline (30 mg/kg, i.p.), a selective α7 nAChR agonist. In transgenic mice overexpressing human tau with N279 K mutation as a model of Alzheimer's disease that showed impaired synaptic plasticity, the levels of PFDN5 mRNA and protein in the hippocampus were significantly decreased in an age-dependent manner as compared with age-matched control. The findings demonstrated that the level of PFDN5 protein in the hippocampus was changed depending on the situation of synaptic plasticity. We propose that PFDN5 could be one of the important components of synaptic plasticity.

• Authors: Keiichi Kadoyama, Kenji Matsuura, Masaoki Takano, Koji Maekura, Yukari Inoue, Shogo Matsuyama
• Journal: Neuroscience letters (Neurosci Lett) Vol. 712 Pg. 134484 (11 01 2019) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 31505240 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Molecular Chaperones
• Nicotinic Agonists
• Nicotinic Antagonists
• prefoldin
• Mecamylamine
• Nicotine

Topics

• Animals
• Gene Expression Regulation
• Hippocampus (drug effects, metabolism)
• Male
• Mecamylamine (pharmacology)
• Mice
• Mice, Transgenic
• Molecular Chaperones (genetics, metabolism)
• Neuronal Plasticity (drug effects, physiology)
• Neurons (drug effects, metabolism)
• Nicotine (pharmacology)
• Nicotinic Agonists (pharmacology)
• Nicotinic Antagonists (pharmacology)
• Synaptic Transmission (drug effects)