The defects of the hippocampal ripples and theta rhythm in depression, and the effects of physical exercise on their amelioration

Shinnosuke Koketsu; Kohki Matsubara; Yoshino Ueki; Yoshiaki Shinohara; Koichi Inoue; Satona Murakami; Takatoshi Ueki

doi:10.1016/j.heliyon.2023.e23738

The defects of the hippocampal ripples and theta rhythm in depression, and the effects of physical exercise on their amelioration

Heliyon. 2023 Dec 16;10(1):e23738. doi: 10.1016/j.heliyon.2023.e23738. eCollection 2024 Jan 15.

Authors

Shinnosuke Koketsu^{1

2

3}, Kohki Matsubara¹, Yoshino Ueki¹, Yoshiaki Shinohara^{2

4}, Koichi Inoue^{2

5}, Satona Murakami¹, Takatoshi Ueki²

Affiliations

¹ Department of Rehabilitation Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan.
² Department of Integrative Anatomy, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, 467-8601, Japan.
³ Department of Physical Therapy, Nagoya Women's University Faculty of Medical Science, Nagoya, Aichi, 467-8610, Japan.
⁴ Department of Anatomy and Cell Biology, Yamanashi University Graduate School of Medical Sciences, Chuo, Yamanashi, 409-3898, Japan.
⁵ Department of Anatomy and Cell Biology, Nara Medical University, Kashihara, Nara, 634-8521, Japan.

Abstract

Adverse environmental stress causes depressive symptoms with the impairments of memory formation, cognition, and motivation, however, their underlying neural bases have not been well understood, especially based on the observation of living animals. In the present study, therefore, the mice model of restraint-induced stress was examined electrophysiologically to investigate the alterations of hippocampal sharp wave ripples (SWRs) and theta rhythms. In addition, the therapeutic effects of physical exercise on the amelioration of those hippocampal impairments were examined in combination with a series of behavioral tests. The data demonstrated that chronic restraint stress caused the reductions of occurrence and amplitude of hippocampal SWRs and the decreases of occurrence, duration, and power of theta rhythms, while physical exercise significantly reverted them to the levels of healthy control. Furthermore, hippocampal adult neurogenesis and microglial activation, previously reported to be involved in the etiology of depression, were histologically examined in the mice. The results showed that the impairment of neurogenesis and alleviation of microglial activation were induced in the depressed mice. On the other hand, physical exercise considerably ameliorated those pathological conditions in the affected brain. Consistently, the data of behavioral tests in mice suggested that physical exercise ameliorated the symptomatic defects of motivation, memory formation, and cognition in the depressed mice. The impairments of hippocampal SWRs and theta rhythms in the affected hippocampus are linked with the symptomatic impairments of cognition and motivation, and the defect of memory formation, respectively, in depression. Taken together, this study demonstrated the implications of impairment of the hippocampal SWRs and theta rhythms in the etiology of depression and their usefulness as diagnostic markers of depression.

Keywords: Depression; Hippocampus; Inflammation; Physical exercise; Sharp wave and ripples; Theta rhythms.