ABSTRACT
The mechanisms of the transplantation of neural stem cells (NSCs) in the treatment of Alzheimer's disease remain poorly understood. In this study, NSCs were transplanted into the hippocampal CA1 region of the rTg (tau P301L) 4510 mouse model, a tauopathy model that is thought to reflect the tau pathology associated with Alzheimer's disease. The results revealed that NSC transplantation reduced the abnormal aggregation of tau, resulting in significant improvements in the short-term memory of the tauopathy model mice. Compared with wild-type and phosphate-buffered saline (PBS)-treated mice, mice that received NSC transplantations were characterized by changes in the expression of multiple proteins in brain tissue, particularly those related to the regulation of tau aggregation or misfolding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) function analysis revealed that these proteins were primarily enriched in pathways associated with long-term potentiation, neurogenesis, and other neurobiological processes. Changes in the expression levels of key proteins were verified by western blot assays. These data provided clues to improve the understanding of the functional capacity associated with NSC transplantation in Alzheimer's disease treatment. This study was approved by the Beijing Animal Ethics Association and Ethics Committee of Beijing Institute of Technology (approval No. SYXK-BIT-school of life science-2017-M03) in 2017.
ABSTRACT
Reduction of hippocampal neurogenesis caused by aging and neurological disorders would impair neural circuits and result in memory loss. A new lead compound (N-trans-3',4'-methylenedioxystilben-4-yl acetamide 27) has been discovered to efficiently stimulate adult rats' neurogenesis. In-depth structure-activity relationship studies proved the necessity of a stilbene scaffold that is absent in highly cytotoxic analogs such as chalcones and heteroaryl rings and inactive analogs such as diphenyl acetylene and diphenyl ethane, and validated the importance of an NH in the carboxamide and a methylenedioxy substituent on the benzene ring. Immunohistochemical staining and biochemical analysis indicate, in contrast to previously reported neuroprotective chemicals, N-stilbenyl carboxamides have extra capacity for neuroproliferation-type neurogenesis, thereby providing a foundation for improving the plasticity of the adult mammalian brain.
Subject(s)
Acetanilides/pharmacology , Drug Discovery , Hippocampus/drug effects , Neurogenesis/drug effects , Plant Extracts/chemistry , Stilbenes/pharmacology , Acetanilides/chemistry , Acetanilides/isolation & purification , Animals , Cell Line, Tumor , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , Male , Molecular Structure , Rats , Rats, Sprague-Dawley , Stilbenes/chemistry , Stilbenes/isolation & purification , Structure-Activity RelationshipABSTRACT
OBJECTIVE: To explore the influence of the DNA repair gene ERCC2 single nucleotide polymorphisms (SNPs) rs13181, rs1618536, and rs1799793 on male idiopathic infertility in Ningxia, China. METHODS: Using MassArray, we conducted a case-control study and genotyped three ERCC2 SNPs rs13181, rs1618536, and rs1799793 for 351 males (aged 31.0 +/- 4.2 years) with idiopathic infertility and another 327 normal fertile men (aged 33.0 +/- 5.9 years) as controls. RESULTS: The ERCC2 AnyG-anyA-anyA genotypes were significantly associated with an increased risk of idiopathic infertility (OR 0.414, 95% CI 0.176 - 0.970), while the three single ERCC2 SNPs rs13181, rs1618536, and rs1799793 showed no significant differences between the cases and controls (P > 0.05). CONCLUSION: The ERCC2 SNPs rs13181, rs1618536, and rs1799793 play a role of interaction in male idiopathic infertility in Ningxia, contributing to the risk of the disease.
