Tags

Type your tag names separated by a space and hit enter

Salsolinol induced apoptotic changes in neural stem cells: amelioration by neurotrophin support.
Neurotoxicology. 2013 Mar; 35:50-61.N

Abstract

Salsolinol (SAL), a catechol isoquinoline has invited considerable attention due to its structural similarity with dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Its high endogenous presence in Parkinsonian brain implicated its possible association with the disease process. SAL is also present in alcohol beverages and certain food materials and can get access to brain especially in conditions of immature or impaired BBB. Besides this, the effect of SAL on neural stem cells (NSCs) which are potential candidates for adult neurogenesis and transplantation mediated rejuvenating attempts for Parkinson's disease (PD) brain has not been known so far. NSCs in both the cases have to overcome suppressive cues of diseased brain for their survival and function. In this study we explored the toxicity of SAL toward NSCs focusing on apoptosis and status of PI3K survival signaling. NSCs cultured from embryonic day 11 rat fetal brain including those differentiated to TH(+ve) colonies, when challenged with SAL (1-100μM), elicited a concentration and time dependent cell death/loss of mitochondrial viability. 10μM SAL on which significant mitochondrial impairment initiated was further used to study mechanism of toxicity. Morphological impairment, enhanced TUNEL positivity, cleaved caspase-3 and decreased Bcl-2:Bax suggested apoptosis. Sal toxicity coincided with reduced pAkt level and its downstream effectors: pCREB, pGSK-3β, Bcl-2 and neurotrophins GDNF, BDNF suggesting repressed PI3K/Akt signaling. Multiple neurotrophic factor support in the form of Olfactory Ensheathing Cell's Conditioned Media (OEC CM) potentially protected NSCs against SAL through activating PI3K/Akt pathway. This was confirmed on adding LY294002 the PI3K inhibitor which abolished the protection. We inferred that SAL exerts substantial toxicity toward NSCs. These findings will lead to better understanding of endogenous threats that might affect the fate of transplanted NSCs and their probable antidotes.

Authors+Show Affiliations

Indian Institute of Toxicology Research (CSIR), Developmental Toxicology Division, Mahatma Gandhi Marg, Post Box 80, Lucknow 226 001, India; Department of Microbiology, IMS, Banaras Hindu University, Varanasi 221 005, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23261589

Citation

Shukla, A, et al. "Salsolinol Induced Apoptotic Changes in Neural Stem Cells: Amelioration By Neurotrophin Support." Neurotoxicology, vol. 35, 2013, pp. 50-61.
Shukla A, Mohapatra TM, Agrawal AK, et al. Salsolinol induced apoptotic changes in neural stem cells: amelioration by neurotrophin support. Neurotoxicology. 2013;35:50-61.
Shukla, A., Mohapatra, T. M., Agrawal, A. K., Parmar, D., & Seth, K. (2013). Salsolinol induced apoptotic changes in neural stem cells: amelioration by neurotrophin support. Neurotoxicology, 35, 50-61. https://doi.org/10.1016/j.neuro.2012.12.005
Shukla A, et al. Salsolinol Induced Apoptotic Changes in Neural Stem Cells: Amelioration By Neurotrophin Support. Neurotoxicology. 2013;35:50-61. PubMed PMID: 23261589.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Salsolinol induced apoptotic changes in neural stem cells: amelioration by neurotrophin support. AU - Shukla,A, AU - Mohapatra,T M, AU - Agrawal,A K, AU - Parmar,D, AU - Seth,K, Y1 - 2012/12/21/ PY - 2012/08/11/received PY - 2012/12/14/revised PY - 2012/12/14/accepted PY - 2012/12/25/entrez PY - 2012/12/25/pubmed PY - 2013/9/11/medline SP - 50 EP - 61 JF - Neurotoxicology JO - Neurotoxicology VL - 35 N2 - Salsolinol (SAL), a catechol isoquinoline has invited considerable attention due to its structural similarity with dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Its high endogenous presence in Parkinsonian brain implicated its possible association with the disease process. SAL is also present in alcohol beverages and certain food materials and can get access to brain especially in conditions of immature or impaired BBB. Besides this, the effect of SAL on neural stem cells (NSCs) which are potential candidates for adult neurogenesis and transplantation mediated rejuvenating attempts for Parkinson's disease (PD) brain has not been known so far. NSCs in both the cases have to overcome suppressive cues of diseased brain for their survival and function. In this study we explored the toxicity of SAL toward NSCs focusing on apoptosis and status of PI3K survival signaling. NSCs cultured from embryonic day 11 rat fetal brain including those differentiated to TH(+ve) colonies, when challenged with SAL (1-100μM), elicited a concentration and time dependent cell death/loss of mitochondrial viability. 10μM SAL on which significant mitochondrial impairment initiated was further used to study mechanism of toxicity. Morphological impairment, enhanced TUNEL positivity, cleaved caspase-3 and decreased Bcl-2:Bax suggested apoptosis. Sal toxicity coincided with reduced pAkt level and its downstream effectors: pCREB, pGSK-3β, Bcl-2 and neurotrophins GDNF, BDNF suggesting repressed PI3K/Akt signaling. Multiple neurotrophic factor support in the form of Olfactory Ensheathing Cell's Conditioned Media (OEC CM) potentially protected NSCs against SAL through activating PI3K/Akt pathway. This was confirmed on adding LY294002 the PI3K inhibitor which abolished the protection. We inferred that SAL exerts substantial toxicity toward NSCs. These findings will lead to better understanding of endogenous threats that might affect the fate of transplanted NSCs and their probable antidotes. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/23261589/Salsolinol_induced_apoptotic_changes_in_neural_stem_cells:_amelioration_by_neurotrophin_support_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(12)00306-3 DB - PRIME DP - Unbound Medicine ER -