Hippocampal long-term potentiation is modulated by exercise-induced alterations in dopaminergic synaptic transmission in mice selectively bred for high voluntary wheel running.
Jessica Mai-Phuong Phan, Jiwon Yi, Julia Hope Amor Foote, Asia Rei Katsura Ayabe, Kevin Guan, Theodore Garland, Karen Diane Parfitt
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引用次数: 0
Abstract
Background: High-Runner (HR) mice, selectively bred for increased voluntary wheel running behavior, exhibit heightened motivation to run. Exercise has been shown to influence hippocampal long-term potentiation (LTP) and memory, and is neuroprotective in several neurodegenerative diseases.
Objective: This study aimed to determine the impact of intense running in HR mice with wheel access on hippocampal LTP, compared to HR mice without wheels and non-selected control (C) mice with/without wheels. Additionally, we investigated the involvement of D1/D5 receptors and the dopamine transporter (DAT) in LTP modulation and examined levels of these proteins in HR and C mice.
Methods: Adult female HR and C mice were individually housed with/without running wheels for at least two weeks. Hippocampal LTP of extracellular field excitatory postsynaptic potentials (fEPSPs) was measured in area CA1, and SKF-38393 (D1/D5 receptor agonist) and GBR 12909 (DAT inhibitor) were used to probe the role of D1/D5 receptors and DAT in LTP differences. Western blot analyses assessed D1/D5 receptor and DAT expression in the hippocampus, prefrontal cortex, and cerebellum.
Results: HR mice with wheel access showed significantly increased hippocampal LTP compared to those without wheels and to C mice with/without wheels. Treatment with SKF-38393 or GBR 12909 prevented the heightened LTP in HR mice with wheels, aligning it with levels in C mice. Hippocampal D1/D5 receptor levels were lower, and DAT levels were higher in HR mice compared to C mice. No significant changes were observed in other brain regions.
Conclusions: The increased hippocampal LTP seen in HR mice with wheel access may be related to alterations in dopaminergic synaptic transmission that underlie the neurophysiological basis of hyperactivity, motor disorders, and/or motivation.
期刊介绍：
This interdisciplinary journal publishes papers relating to the plasticity and response of the nervous system to accidental or experimental injuries and their interventions, transplantation, neurodegenerative disorders and experimental strategies to improve regeneration or functional recovery and rehabilitation. Experimental and clinical research papers adopting fresh conceptual approaches are encouraged. The overriding criteria for publication are novelty, significant experimental or clinical relevance and interest to a multidisciplinary audience. Experiments on un-anesthetized animals should conform with the standards for the use of laboratory animals as established by the Institute of Laboratory Animal Resources, US National Academy of Sciences. Experiments in which paralytic agents are used must be justified. Patient identity should be concealed. All manuscripts are sent out for blind peer review to editorial board members or outside reviewers. Restorative Neurology and Neuroscience is a member of Neuroscience Peer Review Consortium.
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