The Effect of Topiramate on the Cerebellum of the Obese Female Rats: A Stereological, Histochemical and Bioinformatical Study by Investigation of TNF-α Interaction

The rising incidence of obesity underscores the necessity for alternative obesity treatments. Patients commonly prefer medication aiding in weight reduction. Topiramate, an antiepileptic drug, is gaining popularity among obese patients for its weight loss benefits. This study aims to explore Topiramate's impact on the cerebella of obese female rats. In the experiment, 24 female rats (200–250 g) were divided into four groups: non-obese control (NOC), obese control (OC), non-obese topiramate (NOT) and obese topiramate (OT). The non-obese rats were given a standard diet, while the obese rats received a high-fat diet (40% fat). After 9 weeks, topiramate was administered intraperitoneally daily for 6 weeks. Following this, the rats were euthanised, and their cerebella were removed. The volume of the cerebellum and mean numerical density of the molecular neurons, granular neurons and Purkinje cells were estimated using stereological methods, and the link between obesity-caused cerebellum damage and TNF-α was assessed through immunohistochemical and bioinformatic techniques. Additionally, histopathological evaluations of the tissues were conducted. The cerebellar volume in the OC group was decreased compared to the NOC group. The topiramate groups exhibited a decrease in molecular or/and granular neuron numbers in the NOT and OT groups. Notably, neurons with dark cytoplasm were observed in the topiramate-treated groups, alongside neuronal degeneration was seen in the obese groups. The connection between TNF-α and obesity or obesity-caused cerebellum damage was confirmed through both immunohistochemical and bioinformatics analyses. These findings suggest that topiramate might have a degenerative effect on the cerebellum, especially following obesity.