The neuroprotective effect of exogen melatonin upon fetal hippocampus damage caused by high‐dose caffeine administration in pregnant rats

• Published in: International journal of developmental neuroscience Vol. 84; no. 3; pp. 251 - 261
• Main Authors: Köse, Yağmur, Şirin, Cansın, Turgut, Ali Çağlar, Tomruk, Canberk, Uyanıkgil, Yiğit, Turgut, Mehmet
• Format: Journal Article
• Language: English
• Published: United States 01-05-2024
• Subjects: caffeine; fetus; hippocampus; melatonin; pregnancy; rat; caffeine; hippocampus; rat; melatonin; fetus; pregnancy
• ISSN: 0736-5748; 1873-474X
• DOI: 10.1002/jdn.10323

Objective
The aim of this study is to evaluate whether exogenous melatonin (MEL) mitigates the deleterious effects of high‐dose caffeine (CAF) administration in pregnant rats upon the fetal hippocampus.
Materials and methods
A total of 32 adult Wistar albino female rats were divided into four groups after conception (n = 8). At 9–20 days of pregnancy, intraperitoneal (i.p.) MEL was administered at a dose of 10 mg/kg/day in the MEL group, while i.p. CAF was administered at a dose of 60 mg/kg/day in the CAF group. In the CAF plus MEL group, i.p. CAF and MEL were administered at a dose of 60 and 10 mg/kg/day, respectively, at the same period. Following extraction of the brains of the fetuses sacrificed on the 21st day of pregnancy, their hippocampal regions were analyzed by hematoxylin and eosin and Cresyl Echt Violet, anti‐GFAP, and antisynaptophysin staining methods.
Results
While there was a decrease in fetal and brain weights in the CAF group, it was found that the CAF plus MEL group had a closer weight average to that of the control group. Histologically, it was observed that the pyramidal cell layer consisted of 8–10 layers of cells due to the delay in migration in hippocampal neurons in the CAF group, while the MEL group showed similar characteristics with the control group. It was found that these findings decreased in the CAF plus MEL group.
Conclusion
It is concluded that high‐dose CAF administration causes a delay in neurogenesis of the fetal hippocampus, and exogenous MEL is able to mitigate its deleterious effects.
A high‐dose caffeine (CAF) in pregnant rats caused a delay in migration of hippocampal neurons, but addition of exogenous melatonin was helpful in mitigating deleterious effects of the CAF. Thus, it is recommended that use of CAF should be limited during pregnancy to avoid its potential negative effects on the fetus.