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Type-1 diabetes mellitus down-regulated local cerebral glial fibrillary acidic protein expression in experimental toxoplasmosis

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Abstract

Cerebral toxoplasmosis is an opportunistic infection, occurring mostly in immunosuppressed patients due to the reactivation of latent Toxoplasma cysts. The cerebral comorbidity in diabetic patients tends to intensify the burden of pathogenic infection within the brain. The aim of this work was to study the effect of cerebral toxoplasmosis in experimentally infected hyperglycemic mice, on histopathology and glial fibrillary acidic protein (GFAP) expression, compared to normoglycemic mice at different time intervals. Vasculopathy was exclusively observed in diabetic groups, with features of increased severity during Toxoplasma infection. Gliosis was observed in diabetic groups, while hyperactive astroglial activity was detected in normoglycemic groups, especially at 6 weeks of infection. GFAP expression showed significant up-regulation in normoglycemic mice at 6 weeks of infection (40.03 ± 1.41) afterwards, it decreased to 22.22 ± 3.14 at 12 weeks which was statistically insignificant to the normal level, possibly indicating the successful Toxoplasma stage transformation (to bradyzoite), thereby limiting the infection within the brain. In hyperglycemic infected groups, GFAP was significantly down-regulated, in both acute and chronic phases of infection, most likely indicating failure of stage transformation and infection limitation. This may expose those vulnerable groups to the risk of dissemination, resulting in life-threatening diffuse encephalitis. The current study emphasized the importance of rapid diagnosis of Toxoplasma infection in diabetic subjects, and highlighted the value of using GFAP as a neurological indicator of disease progression in those comorbid cases.

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Data availability

The data that support the findings of this study are available from the corresponding author (Hanaa Omar Fadl), upon reasonable request.

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Acknowledgements

We would like to express our gratitude to all the members that collaborated in this study.

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AAA and MAS; Methodology: GAA, M-EAF and MAB; Data collection and analysis: AAA, MAS, MAB and GAA; Writing the paper: HOF, AAA and M-EAF; Reviewing and editing: HOF, AAA, AAA and M-EAF. All authors reviewed the manuscript.

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Correspondence to Hanaa Omar Fadl.

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The study protocol was approved by the ethical committee of Kasr-Alainy School of Medicine, Theodor Bilharz Research Institute (TBRI), and The Institutional Animal Care & Use Committee (IACUC) of Cairo University (research number: CU-IACUC, III-38-21).

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Abdelhamid, G.A., Abdelaal, A.A., Shalaby, M.A. et al. Type-1 diabetes mellitus down-regulated local cerebral glial fibrillary acidic protein expression in experimental toxoplasmosis. J Parasit Dis 47, 319–328 (2023). https://doi.org/10.1007/s12639-023-01573-y

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