The Effect of NeuroAid (MLC901) on Cholestasis-Induced Spatial Memory Impairment with Respect to the Expression of BAX, BCL-2, BAD, PGC-1α and TFAM Genes in the Hippocampus of Male Wistar Rats.

Abstract	Cholestasis is a bile flow reduction that is induced following Bile Duct Ligation (BDL). Cholestasis impairs memory and induces apoptosis. Apoptosis consists of two pathways: intrinsic and extrinsic. The intrinsic pathway is modulated by BCL-2 (B cell lymphoma-2) family proteins. BCL-2 (a pro-survival BCL-2 protein) has anti-apoptotic effect, while BAD (BCL-2-associated death) and BAX (BCL-2-associated X), the other members of BCL-2 family have pro-apoptotic effect. Furthermore, TFAM (mitochondrial transcriptional factor A) is involved in transcription and maintenance of mitochondrial DNA and PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) is a master regulator of mitochondrial biogenesis. On the other hand, NeuroAid is a Traditional Chinese Medicine with neuroprotective and anti-apoptosis effects. In this study, we evaluated the effect of cholestasis on spatial memory and expression of BCL-2, BAD, BAX, TFAM, and PGC-1α in the hippocampus of rats. Additionally, we assessed the effect of NeuroAid on cholestasis-induced cognitive and genetic alterations. Cholestasis was induced by BDL surgery and NeuroAid was injected intraperitoneal at the dose of 0.4 mg/kg. Furthermore, spatial memory was evaluated using Morris Water Maze (MWM) apparatus. The results showed cholestasis impaired spatial memory, increased the expression of BAD and BAX, decreased the expression of TFAM and PGC-1α, and did not alter the expression of BCL-2. Also, NeuroAid decreased the expression of BAD and BAX and increased the expression of TFAM, PGC-1α, and BCL-2. In conclusion, cholestasis impaired spatial memory and increased the expression of pro-apoptotic genes. Also, cholestasis decreased the expression of TFAM and PGC-1α. Interestingly, NeuroAid restored the effects of cholestasis.
Authors	Pejman Molaei, Salar Vaseghi, Maliheh Entezari, Mehrdad Hashemi, Mohammad Nasehi
Journal	Neurochemical research (Neurochem Res) Vol. 46 Issue 8 Pg. 2154-2166 (Aug 2021) ISSN: 1573-6903 [Electronic] United States
PMID	34031842 (Publication Type: Journal Article)
Chemical References	Bad protein, rat Bax protein, rat Bcl2 protein, rat Drugs, Chinese Herbal Neuroaid Neuroprotective Agents Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Ppargc1a protein, rat Proto-Oncogene Proteins c-bcl-2 Tfam protein, rat Transcription Factors bcl-2-Associated X Protein bcl-Associated Death Protein
Topics	Animals Apoptosis (drug effects) Bile Ducts (surgery) Cholestasis (complications, metabolism) Drugs, Chinese Herbal (therapeutic use) Gene Expression (drug effects) Hippocampus (drug effects, metabolism) Ligation Male Memory Disorders (drug therapy, etiology) Morris Water Maze Test (drug effects) Neuroprotective Agents (therapeutic use) Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (genetics) Proto-Oncogene Proteins c-bcl-2 (genetics) Rats, Wistar Spatial Memory (drug effects) Transcription Factors (genetics) bcl-2-Associated X Protein (genetics) bcl-Associated Death Protein (genetics) Rats

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