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Neuroprotective and Immunomodulatory effects of human hair follicle stem cells on streptozotocin-induced memory impairment in rats: insights into inflammation and neurotrophic mechanisms.

PMID: 41369702 · DOI: 10.1007/s11033-025-11341-1 · Molecular biology reports, 2025 · Etrat Hooshmandi, Elahe Rafiei, Maryam Owjfard, Yasaman Mohammadi, Farhad Koohpeyma, Leila Simani, Mohammad Sadegh Safar
📄 Abstract

Alzheimer's disease (AD), a primary cause of dementia, involves cognitive decline and neuroinflammation. Human hair follicle stem cells (hHFSCs) have shown neuroprotective potential, but their effects on immune modulation, especially in xenogeneic transplantation, remain unclear. This study aimed to investigate the therapeutic potential of hHFSCs against memory impairment and neuroinflammation induced by streptozotocin (STZ) in male rats. Adult male Sprague-Dawley rats were intracerebroventricularly injected with STZ (3 mg/kg) to induce AD-like cognitive deficits. hHFSC transplantation (1 × 10 STZ significantly impaired memory in passive avoidance test, but not Y-maze. hHFSC significantly improved memory performance. mRNA analysis revealed elevated BDNF, TGFβ, and GFAP levels in the STZ group. The increased TGFβ and GFAP levels continued following hHFSC treatment, indicating a compensatory response. Moreover, pro-inflammatory factors (IL-1β, IL-6, and TNFα) were upregulated following hHFSC therapy, suggesting persistent neuroinflammation. hHFSC led to anti-inflammatory effects through the elevation of IL-10. In addition, hHFSCs significantly reduced hippocampal atrophy and neuronal loss induced by STZ. hHFSCs exhibit partial neuroprotective effects against STZ-induced memory impairment. The simultaneous upregulation of pro- and anti-inflammatory markers underscores the complexity of the inflammatory response in this xenogeneic model. Future investigations should consider immunocompromised models or immunosuppressive protocols better to isolate the therapeutic effects of hHFSCs from immune responses.

Confidence: 0.36 · 3 полей извлечено
Идентификация (6 полей)
Механизм действия (21 полей)
Экспрессия (8 полей)
Tissue expression
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In vitro
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In vivo
Intracerebroventricular injection of streptozotocin (3 mg/kg) in adult male Sprague-Dawley rats to induce AD-like cognitive deficits, followed by transplantation of human hair follicle stem cells (hHFSCs) (1×10^? cells). Behavioral tests (passive avoidance, Y-maze), mRNA analysis (BDNF, TGFβ, GFAP, IL-1β, IL-6, TNFα, IL-10), and histological assessment of hippocampal atrophy and neuronal loss were performed.
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In silico
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Genetic association
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Ex vivo
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Animal model
Adult male Sprague-Dawley rats
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Diet/model
Streptozotocin (STZ)-induced memory impairment model (intracerebroventricular injection, 3 mg/kg)
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Клиника (11 полей)