Electroacupuncture Enhances Neuroplasticity by Regulating the Orexin A-Mediated cAMP/PKA/CREB Signaling Pathway in Senescence-Accelerated Mouse Prone 8 (SAMP8) Mice.

Zhitao Hou,Xinyu Yang,Jing Chen,Hongcai Shang,Yang Li,Fushun Wang

doi:10.1155/2022/8694462

Abstract

Learning and memory disorders and decreased neuroplasticity are the main clinical manifestations of age-induced cognitive dysfunction. Orexin A (OxA) has been reported to show abnormally elevated expression in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and to be associated with cognitive impairment. Here, we further assessed whether the excitatory neurotransmitter OxA is involved in neuroplasticity and cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice. In this study, we investigated the mechanism of OxA by using behavioral tests, CSF microdialysis, immunofluorescence, toluidine blue staining, gene silencing, transmission electron microscopy, and Western blotting. The results showed that 10 Hz electroacupuncture (EA) effectively alleviated learning and memory impairment in 7-month-old SAMP8 mice, reduced OxA levels in the CSF, increased the level of the neurotransmitter glutamate, alleviated pathological damage to hippocampal tissue, improved the synaptic structure, enhanced synaptic transmission, and regulated the expression of cAMP/PKA/CREB signaling pathway-related proteins. These results suggest that EA enhances neuroplasticity in SAMP8 mice by regulating the OxA-mediated cAMP/PKA/CREB signaling pathway, thus improving cognitive function. These findings suggest that EA may be beneficial for the prevention and treatment of age-induced cognitive impairment.

Highlights

Cognitive impairment is a neurodegenerative disease that seriously affects the health of elderly individuals [1]
Orexin A (OxA)/hypocretin 1 is an excitatory neuropeptide that is synthesized by neurons located in the lateral hypothalamus, distributed in most brain regions, including the hippocampus, and plays an important role in the initiation and maintenance of wakefulness [3]
Clinical studies have reported that patients with increased levels of OxA in the cerebrospinal fluid (CSF) often present with circadian rhythm disturbances [5, 6], decreased synaptic plasticity [7, 8], and neurotransmitter transport dysfunction [9, 10], as well as changes in the expression of Alzheimer’s disease (AD)-related biomarkers, such as increased levels of phosphorylated Tau and Aβ in the CSF [11, 12]

Summary

Introduction

Cognitive impairment is a neurodegenerative disease that seriously affects the health of elderly individuals [1]. We propose that age-related degeneration of synapses may be an important focus for elucidating the mechanism of Alzheimer’s disease (AD) because synapses are the cellular basis for the information process, memory formation, movement, sensations, emotions, and skills. The OxA receptor OX1R/HCRT1R is a G protein-coupled receptor involved in a variety of physiological functions, including learning and memory [4]. Clinical studies have reported that patients with increased levels of OxA in the cerebrospinal fluid (CSF) often present with circadian rhythm disturbances [5, 6], decreased synaptic plasticity [7, 8], and neurotransmitter transport dysfunction [9, 10], as well as changes in the expression of AD-related biomarkers, such as increased levels of phosphorylated Tau and Aβ in the CSF [11, 12]. Patients with AD with abnormally elevated OxA levels always exhibit a significantly poorer

Methods

Results

Conclusion