Toxoplasma gondii induce apoptosis of neural stem cells via endoplasmic reticulum stress pathway
Authors: Teng Wang
Li Yu
Hua Wang
Yongzhong Wang
Xiaojuan Ding
Jie Zhou
Jian DU
Lingzhi Chen
Xiaofeng Gan
Jilong Shen
Journal: Parasitology (2014)
Discipline: MICROBIOLOGY
Keywords: Toxoplasma gondii; congenital brain disease; neuropathogenesis; neural stem cells; apoptosis
Affiliations: Department of Microbiology and Parasitology, Anhui Provincial Laboratory of Microbiology and Parasitology, Anhui Key Laboratory of Zoonoses, Anhui Medical University, Hefei 230032, PR China., School of Life Sciences, Anhui University, Hefei 230039, PR China., Department of Biochemistry, Anhui Medical University, Hefei 230032, PR China.

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. 

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PubPeer comments:
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 *[right]* Figs 5a,b,c,  Fig. 5 Animal studies of the Chit-DNA-VL nanospheres. b Group 1 of mice that received Chit-VLDNA nanospheres formulation successfully maintained the higher levels of GLP1 GIP in the blood for the prolonged time than the group 2 receiving free VL solution. c Group 1 of mice that received Chit-VL-DNA nanospheres formulation maintained better glycemic control for the prolonged time than the group 2 receiving blank nanospheres without VL. d Plasma drug concentration with time . *[left]* Figs 6A,B,C from [Baig et al (2019)] ,  Results of oral administration of Chit EudDNA-VL hybrid nanospheres: A) Group 1 treated with the hybrid nanospheres showed sustained plasma elevation of the GLP1 levels than that of receiving free VL solution. B) Group 1 treated with the hybrid nanospheres showed better and consistent control of the glycemic levels than that of receiving free VL solution. C) The variations of plasma drug levels with time. ![file] Surprisingly similar results from two different materials. Presumably different experiments, because the error bars are not the same. , 
 Fig 6d,  After completing the treatment duration, pancreas of the sacrificed mice was examined to observe the histology that showed no harm to the islets of Langerhans and intestinal cancers. Panels overlap. ![file] , 
 #4 ![] A third sighting! Fig 5A,B,D from [Baig et al (2019b)] : ![] , 
 *[left]* Fig 5A from  Vildagliptin loaded triangular DNA nanospheres coated with eudragit for oral delivery and better glycemic control in type 2 diabetes mellitus ([Baig et al 2019a] ,  FTIR of (a) formulation V3, (b) V6, (c) Eud-DNA nanospheres without VG (d) Pure VG. All the formulations containing VG showed characteristic VG peak at 1654 nm proved that VG is chemically unchanged . *[middle]* Fig 5A from  Evaluation of chitosan eudragit hybrid coating over cubic DNA nanospheres with superior stability and therapeutic outcomes ([Baig et al 2019b] ),  FTIR analysis depicted chemical and physical stability visualizing all important peaks with slight shifts due to physical entrapments . The direction of the horizontal axis is not consistent across panels. *[right]* Fig 3b from the present paper,  FTIR analysis of the NPs showing chemical stability of the DNA and the VL with the chitosan showing all the individual peaks clearly. ![file] The descriptions of the NPs is not entirely consistent. Using triangular vs. cubic DNA constructs as cores for the NPs seems to make no difference at all. , 
 Sorry, these all belonged to a same project. Need to see if results overlapped. Thanks for pointing out. , 
 *[below]* Fig 5a,  Histological studies showed no damage to any of the pancreatic cells at the end of treatment . *[above]* Fig 4A from [Baig et al (2019)] ,  The prolonged release nanospheres had no damage to the endocrine portion of the pancrease after 5 months compared to the administration of the free VI solution . ![file] Unexpected overlaps (after rotation, color inversion). ,