Temporal expression profiles of microRNAs associated with acute phase of brain ischemia in gerbil hippocampus

Yasuhiro Hamada; Tadayuki Takata; Hisakazu Iwama; Rie Kawakita; Wakako Nonaka; Kazushi Deguchi; Hideki Kobara; Asahiro Morishita; Osamu Miyamoto; Takehiro Nakamura; Toshifumi Itano; Tsutomu Masaki

doi:10.1016/j.heliyon.2024.e28875

Temporal expression profiles of microRNAs associated with acute phase of brain ischemia in gerbil hippocampus

Heliyon. 2024 Mar 29;10(7):e28875. doi: 10.1016/j.heliyon.2024.e28875. eCollection 2024 Apr 15.

Authors

Affiliations

¹ Department of Neurology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kagawa, 761-0793, Japan.
² Life Science Research Center, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kagawa, 761-0793, Japan.
³ Department of General Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kagawa, 761-0793, Japan.
⁴ Department of Gastroenterology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki, Kagawa, 761-0793, Japan.
⁵ Department of Medical Engineering, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare, 288 Matsushima, Kurashiki, 701-0193, Japan.
⁶ Department of Physiology 2, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 701-0192, Japan.

Abstract

Neuroprotective therapeutic potential for restoring dysregulated microRNA (miRNA) expression has previously been demonstrated in a gerbil cerebral infarction model. However, since temporal changes in miRNA expression profiles following stroke onset are unknown, miRNAs proving to be useful therapeutic targets have yet to be identified. We evaluated cognitive function, hippocampal neuronal cell death, and microarray-based miRNA expression profiles at 5, 9, 18, 36, and 72 h after 5-min whole brain ischemia in gerbils. A decline in cognitive function occurred in parallel with increased neuronal cell death 36-72 h after ischemia. The Jonckheere-Terpstra test was used to analyze miRNA expression trends 5-72 h after ischemia. The expression levels of 63 miRNAs were significantly upregulated, whereas 32 miRNAs were significantly downregulated, monotonically. Of the 32 monotonically downregulated miRNAs, 18 showed the largest decrease in expression 5-9 h after ischemia. A subset of these dysregulated miRNAs (miR-378a-5p, miR-204-5p, miR-34c-5p, miR-211-5p, miR-34b-3p, and miR-199b-3p) could be associated with brain ischemia and neuropsychiatric disorders.

Keywords: Gerbil; Hippocampus; Ischemic stroke; microRNA.