Effects of vitamin D on neurotoxicity, neuroinflammation, and emotional behaviors in offspring of mice administered propofol anesthesia during pregnancy

bjective: This study aimed to investigate the neuroprotective and anti inflammatory effects of vitamin D on propofol-induced neurotoxicity, neuroinflammation, and changes in emotional behavior in the offspring of mice that received general anesthesia during pregnancy. Methods: Twenty pregnant Swiss albino mice, each 8 weeks old, were divided into four groups of five mice each: control (Group K), vitamin D (Group D), propofol (Group P), and propofol with vitamin D (Group PD). On the 14th day of pregnancy, Groups P and PD received 200 mg/kg of intraperitoneal propofol. Throughout pregnancy, Groups D and PD received 5 mcg/kg/day of vitamin D, while Groups P and K received 1 ml of saline intraperitoneally. Newborn mice from these groups were included in the study. Twelve offspring from each group were examined using electron microscopy (EM) and immunohistochemistry (IHC) to assess prefrontal cortex and hippocampus tissue sections for the expression of Interleukin-6 (IL-6), Brain-Derived Neurotrophic Factor (BDNF), Tumor Necrosis Factor-α (TNF-α), c-Fos, B-cell Lymphoma 2 (Bcl-2), Bcl-2-associated X Protein (Bax), and Oligodendrocyte Transcription Factor 2 (Olig2). Behavioral tests, including the open field and elevated plus maze tests, were conducted on the 45th day for mice that were not part of the IHC and EM experiments. Results: On postnatal days 7 and 45, IHC analysis revealed that in Group P, the expression of Bax, IL-6, TNF-α, and c-Fos in prefrontal cortex and hippocampus tissues was significantly increased, while the expression of Bcl-2, Olig2, and BDNF was significantly decreased compared to Group PD. These findings were supported by EM images. No significant differences were found in behavioral tests among the groups. Conclusion: Our study suggests that neuroinflammation and neurotoxicity induced by exposure to propofol on the 14th day of pregnancy can be mitigated by prophylactic vitamin D treatment throughout pregnancy. Keywords: Propofol, vitamin D, IL-6, BDNF, Bax, TNF-α, c-Fos, Bcl-2, Olig2, EM