Transcriptomic profiling of the hypothalamus in a neonatal STZ-induced diabetes model: effects of Curcumin and Aged Garlic Extract.

Type 2 Diabetes Mellitus (T2DM) is associated with a state of chronic low-grade inflammation that severely affects the central nervous system, particularly the hypothalamus, which acts as the master regulator of energy homeostasis. This study aimed to characterize the hypothalamic transcriptomic signature in a complex murine model of T2DM induced by neonatal administration of Streptozotocin (nSTZ, 70 mg/kg) followed by a chronic High-Fat Diet (HFD, 60% kcal from fat). Given the neuroprotective properties of natural polyphenols, we evaluated the modulatory effects of Curcumin (50 mg/kg) and Aged Garlic Extract (EAE, 200 mg/kg) administered daily via oral gavage for 28 days. By employing high-throughput RNA sequencing (RNA-seq), we identified differentially expressed genes (DEGs) and perturbed molecular pathways involved in neuroinflammation, synaptic plasticity and gabaergic system. Our findings provide a comprehensive map of the gene expression changes associated with diabetic neurodegeneration and the therapeutic potential of nutraceutical interventions to restore hypothalamic function.