Dose-dependent effects of Linalool treatment on cerebellarmorphology in rats with diabetic neuropathy

Diabetes mellitus is a multisystemic, multifactorial disease characterized with hyperglisemia, oxidative stress and inflamatory processes. One of its most important complications, diabetic neuropathy, primarily manifests as distal symmetric polyneuropathy. Damage that develops in peripheral nerves leads to pain and progressive hypoesthesia. Recent studies show that diabetes is not limited to peripheral nerves but also causes morphological changes in the central nervous system. The cerebellum, known for its role in balance and motor control, receives intense sensory input from both the periphery and the brain while performing these tasks, and thus plays a critical role in pain modulation. In this study, the dose- dependent effects of Linalool treatment on cerebellar morphology were investigated in rats with diabetic neuropathy. Adult rats with an experimentally induced diabetes model were administered 75 mg/kg and 150 mg/kg of Linalool intraperitoneally for 14 days. Gabapentin was used as a positive control. After treatment, the rats were fixed by intracardiac perfusion and cerebellar sections were stained with toluidine blue to examine under microscope. Volumetric assessments were carried out using the Cavalieri method.No significant differences were detected between groups in terms of cerebellar cortex layers and white matter volumes. However, the increase in the white matter/cortex ratio observed in the diabetes group was found to return to normal in the Linalool-treated groups. Gabapentin, on the other hand, was not effective on this parameter. The findings indicate that Linalool might be effective in cerebellar pathologies in diabetic rats through its antioxidant, anti-inflammatory, and neuroprotective properties. Considering the complex pathophysiology of diabetes extending from the periphery to the central nervous system, it was concluded that multi-targeted treatment options such as Linalool are clinically promising. Key words: Cerebellum, diabetes, linalool, rat, peripheral neuropathy