Effects of saffron and estrogen on cognition and glial cells in a menopausal demyelination model

Taherianfard, Mahnaz; Javid, Zahra; Sajedianfard, Javad; Khodakaram Tafti, Azizollah

doi:10.22038/ajp.2026.27760

Effects of saffron and estrogen on cognition and glial cells in a menopausal demyelination model

Articles in Press

Document Type : Original Research Article

Authors

¹ Basic Science Dept. School of Vet Med, Shiraz University

² Basic Science Department, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.

³ Basic Science Department, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

⁴ Pathobiological Science Department, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

10.22038/ajp.2026.27760

Abstract

Objective: Crocus sativus (Saffron) is a spice that has neuroprotective properties. The present study aimed to investigate how saffron and estrogen might affect behavior, the number of glial fibrillary acidic protein (GFAP)-positive astrocytes and the number of oligodendrocyte transcription factor 2 (Olig2)-positive cells in menopausal, demyelinated rats.
Materials and methods: Seventy-five female Sprague-Dawley rats weighing 200-250 g were divided to five group; Control, Treatment Control 1, Treatment Control 2, Saffron treatment and Estrogen Treatment. Demyelination was induced by a single injection of 3 µl of 0.01% ethidium bromide (EB) into the dentate gyrus (DG). Saffron aquatic extract dose was 60 mg/kg/day given orally for 21 days and estrogen dose was 5 μg/kg/day given for 7 days. By ovariectomy (OVX), both ovaries were removed. Cognitive behaviors were assessed using the Morris water maze (MWM) test. Immunohistochemistry and ImageJ software quantified the numbers of GFAP- and Olig2-positive cells.
Results: Demyelination resulted in impaired hippocampal histopathology. It also caused deficits in MWM performance. The extent of blood-brain barrier (BBB) disruption was significantly greater (p<0.05) in the treatment control groups compared to the other groups. The numbers of GFAP-positive astrocytes and Olig2-positive oligodendrocytes were significantly reduced (p<0.01) in both treatment groups relative to the other groups
Conclusion: Results indicate that saffron and estrogen have similar effects on reducing demyelination impairment. They improve histopathological defects, MWM performance, and BBB dysfunction. This may be related to the changes in the number of GFAP- and Olig2-positive cells.

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