title: Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway.
abstract: Toxoplasma gondii is a major cause of congenital brain disease; however, the underlying mechanism of neuropathogenesis in brain toxoplasmosis remains elusive. To explore the role of T. gondii in the development of neural stem cells (NSCs), NSCs were isolated from GD14 embryos of ICR mice and were co-cultured with tachyzoites of T. gondii RH strain. We found that apoptosis levels of the NSCs co-cultured with 1×106 RH tachyzoites for 24 and 48 h significantly increased in a dose-dependent manner, as compared with the control. Western blotting analysis displayed that the protein level of C/EBP homologous protein (CHOP) was up-regulated, and caspase-12 and c-Jun N-terminal kinase (JNK) were activated in the NSCs co-cultured with the parasites. Pretreatment with endoplasmic reticulum stress (ERS) inhibitor (TUDCA) and caspase-12 inhibitor (Z-ATAD-FMK) inhibited the expression or activation of the key molecules involved in the ERS-mediated apoptotic pathway, and subsequently decreased the apoptosis levels of the NSCs induced by the T. gondii. The findings here highlight that T. gondii induced apoptosis of the NSCs through the ERS signal pathway via activation of CHOP, caspase-12 and JNK, which may constitute a potential molecular mechanism responsible for the cognitive disturbance in neurological disorders of T. gondii.
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Teng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Gan
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Anhui University, Hefei 230039, PR China.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: DU
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Jilong
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D024101:Mitochondrial Proteins / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology*; D013312:Stress, Physiological; D014122:Toxoplasma / Q000502:physiology*
chemical_list: C513674:Apopt1 protein, mouse; D051017:Apoptosis Regulatory Proteins; D024101:Mitochondrial Proteins