Cerebralcare Granule® attenuates cognitive impairment in rats continuously overexpressing microRNA-30e.
Previous studies have demonstrated that dysregulation of micro (mi)RNAs is associated with the etiology of various neuropsychiatric disorders, including depression and schizophrenia. Cerebralcare Granule® (CG) is a Chinese herbal medicine, which has been reported to have an ameliorative effect on brain injury by attenuating blood‑brain barrier disruption and improving hippocampal neural function. The present study aimed to evaluate the cognitive behavior of rats continuously overexpressing miRNA‑30e (lenti‑miRNA‑30e), prior to and following the administration of CG. In addition, the mechanisms underlying the ameliorative effects of CG were investigated. The cognitive ability of the rats was assessed using an open‑field test and a Morris water maze spatial reference/working memory test. A terminal deoxynucleotidyl transferase dUTP nick end labeling assay was used to detect neuronal apoptosis in the dentate gyrus of the hippocampus. Immunohistochemical analysis and western blotting were conducted to detect the expression levels of B‑cell lymphoma 2 (BCL‑2) and ubiquitin‑conjugating enzyme 9 (UBC9), in order to examine neuronal apoptosis. The lenti‑miRNA‑30e rats exhibited increased signs of anxiety, depression, hyperactivity and schizophrenia, which resulted in a severe impairment in cognitive ability. Furthermore, in the dentate gyrus of these rats, the expression levels of BCL‑2 and UBC9 were reduced and apoptosis was increased. The administration of CG alleviated cognitive impairment, enhanced the expression levels of BCL‑2 and UBC9, and reduced apoptosis in the dentate gyrus in the lenti‑miRNA‑30e rats. No significant differences were detected in behavioral indicators between the lenti‑miRNA‑30e rats treated with CG and the normal controls. These findings suggested that CG exerts a potent therapeutic effect, conferred by its ability to enhance the expression levels of BCL‑2 and UBC9, which inhibits the apoptotic process in neuronal cells. Therefore, CG may be considered a potential therapeutic strategy for the treatment of cognitive impairment in mental disorders.
Department of Psychiatry, First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Yong
Y
Xu
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Zhifen
Z
Liu
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Xi
X
Song
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Kerang
K
Zhang
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Xingrong
X
Li
Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Jianhong
J
Li
Department of Psychiatry, First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Xu
X
Yan
Department of Interventional Radiography, Heping Hospital of Changzhi Medical College, Changzhi, Shanxi 046000, P.R. China.
Yuan
Y
Li
Laboratory Animal Facility Biomedical Analysis Center, Tsinghua University, Beijing 100084, P.R. China.
Zhongchen
Z
Xie
Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Hui
H
Zhang
D000818:Animals; D017209:Apoptosis; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D004365:Drugs, Chinese Herbal; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; C553222:cerebralcare preparation; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9