Ischemia-Induced Cognitive Impairment Is Improved via Remyelination and Restoration of Synaptic Density in the Hippocampus after Treatment with COG-Up® in a Gerbil Model of Ischemic Stroke

Tae-Kyeong Lee; Junkee Hong; Ji-Won Lee; Sung-Su Kim; Hyejin Sim; Jae-Chul Lee; Dae Won Kim; Soon Sung Lim; Il Jun Kang; Moo-Ho Won

doi:10.3390/vetsci8120321

Ischemia-Induced Cognitive Impairment Is Improved via Remyelination and Restoration of Synaptic Density in the Hippocampus after Treatment with COG-Up^® in a Gerbil Model of Ischemic Stroke

Vet Sci. 2021 Dec 10;8(12):321. doi: 10.3390/vetsci8120321.

Authors

Tae-Kyeong Lee¹, Junkee Hong², Ji-Won Lee³, Sung-Su Kim³, Hyejin Sim⁴, Jae-Chul Lee⁴, Dae Won Kim⁵, Soon Sung Lim¹, Il Jun Kang¹, Moo-Ho Won⁴

Affiliations

¹ Department of Food Science and Nutrition, Hallym University, Chuncheon 24252, Korea.
² Department of Global Innovative Drug, Chung-Ang University, Seoul 06974, Korea.
³ Famenity Co., Ltd., Uiwang 16006, Korea.
⁴ Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
⁵ Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Kangnung-Wonju National University, Gangneung 25457, Korea.

Abstract

Cerebrovascular disease such as ischemic stroke develops cognitive impairment due to brain tissue damage including neural loss, demyelination and decrease in synaptic density. In the present study, we developed transient ischemia in the forebrain of the gerbil and found cognitive impairment using the Barnes maze test and passive avoidance test for spatial memory and learning memory, respectively. In addition, neuronal loss/death was detected in the Cornu Ammonis 1 (CA1) region of the gerbil hippocampus after the ischemia by cresyl violet histochemistry, immunohistochemistry for neuronal nuclei and histofluorescence with Fluoro-Jade B. Furthermore, in the CA1 region following ischemia, myelin and vesicular synaptic density were significantly decreased using immunohistochemistry for myelin basic protein and vesicular glutamate transporter 1. In the gerbils, treatment with COG-up^® (a combined extract of Erigeron annuus (L.) Pers. and Brassica oleracea Var.), which was rich in scutellarin and sinapic acid, after the ischemia, significantly improved ischemia-induced decline in memory function when compared with that shown in gerbils treated with vehicle after the ischemia. In the CA1 region of these gerbils, COG-up^® treatment significantly promoted the remyelination visualized using immunohistochemistry myelin basic protein, increased oligodendrocytes visualized using a receptor-interacting protein, and restored the density of glutamatergic synapses visualized using double immunofluorescence for vesicular glutamate transporter 1 and microtubule-associated protein, although COG-up^® treatment did not protect pyramidal cells (principal neurons) located in the CA1 region form the ischemic insult. Considering the current findings, a gerbil model of ischemic stroke apparently showed cognitive impairment accompanied by ischemic injury in the hippocampus; also, COG-up^® can be employed for improving cognitive decline following ischemia-reperfusion injury in brains.

Keywords: Cornu Ammonis 1; glutaminergic synapse; ischemia-reperfusion injury; memory function; oligodendrocyte; pyramidal cells.

Abstract

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