title: Streptozotocin Induced Neurotoxicity Involves Alzheimer's Related Pathological Markers: a Study on N2A Cells.
abstract: Intracerebroventricular (icv) injection of streptozotocin (STZ) in rat brain causes prolonged impairment of brain energy metabolism and oxidative damage and leads to cognitive dysfunction; however, its mechanistic specific effects on neurons are not known. The present study was conducted to investigate the STZ-induced cellular and molecular alterations in mouse neuronal N2A cells. The N2A cells were treated with STZ (10, 50, 100, 1000 μM) for 48 h, and different assays were performed. STZ treatment caused significant decrease in cell viability, choline levels, increased acetylcholinesterase (AChE) activity, tau phosphorylation and amyloid aggregation. STZ treatment also led to low levels of glucose uptake, elevated mitochondrial stress, translocation of cytochrome c in cytosol, phosphatidylserine externalization, increased expression of caspase-3 and DNA damage. Co-treatment of clinically used drug donepezil (1 μM) offered significant protection against STZ induced neurotoxicity. Donepezil treatment significantly inhibited the STZ induced neurotoxicity, altered choline level, AChE activity, lowered glucose uptake and mitochondrial stress. However, the caspase-3 expression remains unaltered with co-treatment of donepezil. In conclusion, findings showed that STZ treated N2A cells exhibited the Alzheimer's disease (AD) related pathological markers which are attenuated with co-treatment of donepezil. Findings of the study suggested the potent use of STZ treated N2A cells as in vitro experimental test model to study the disease mechanism at cellular level.
authors.affiliation: Toxicology Division, Central Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India.
authors.forename: Joyshree
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Toxicology Division, Central Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Goswami
authors.affiliation: Toxicology Division, Central Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India.
authors.forename: Sonam
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Toxicology Division, Central Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India.
authors.forename: Chandishwar
authors.initials: C
authors.lastname: Nath
authors.affiliation: Toxicology Division, Central Drug Research Institute (CSIR-CDRI), Lucknow, UP, 226031, India. sarika_singh@cdri.res.in.
authors.forename: Sarika
authors.initials: S
authors.lastname: Singh
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D002794:Choline / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage; D005947:Glucose / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000378:metabolism* / Q000473:pathology*; D010718:Phosphatidylserines / Q000378:metabolism; D010766:Phosphorylation; D066329:Protein Aggregates; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013311:Streptozocin; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000682:Amyloid; D015415:Biomarkers; D010718:Phosphatidylserines; D066329:Protein Aggregates; D012333:RNA, Messenger; D016875:tau Proteins; D013311:Streptozocin; D045304:Cytochromes c; D000110:Acetylcholinesterase; D053148:Caspase 3; D005947:Glucose; D002794:Choline
keywords: Acetylcholinesterase activity; Alzheimer’s disease; Amyloid aggregation; Donepezil; Streptozotocin; Tau phosphorylation
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