Environmental enrichment attenuates astrocyte reactivity and glutamate dysregulation in Streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is associated with central nervous system dysfunction, including astrocyte reactivity and disturbances in excitatory neurotransmission. Increasing evidence suggests that non-pharmacological interventions such as environmental enrichment (EE) may modulate neuroinflammatory and neurochemical alterations in metabolic disorders. However, the combined effects of EE and insulin on astrocyte activation and glutamate homeostasis in DM remain insufficiently characterized. This study investigated the effects of EE, alone and in combination with insulin, on metabolic parameters, pancreatic morphology, astrocyte reactivity, and brain glutamate levels in streptozotocin (STZ)-induced diabetic rats. Thirty male Wistar rats were allocated into five groups: control, DM, diabetic treated with insulin (DM+I), diabetic exposed to EE (DM+EE), and diabetic treated with combined insulin and EE (DM+I+EE). DM was induced using STZ (40 mg/kg, i.p.). Body weight and fasting blood glucose levels were monitored over 30 days. Pancreatic morphology was assessed using hematoxylin and eosin staining. Astrocyte reactivity in brain tissue was evaluated by glial fibrillary acidic protein (GFAP) immunohistochemistry, and glutamate levels were quantified using ELISA. STZ-induced diabetes resulted in significant weight loss, hyperglycaemia, pancreatic islet disruption, increased astrocyte reactivity, and elevated brain glutamate levels compared to controls. Both insulin and EE independently improved metabolic parameters, partially preserved pancreatic morphology, reduced GFAP immunoreactivity, and lowered glutamate levels. Notably, the combined insulin and EE intervention produced the most pronounced improvements across metabolic, histological, and neurochemical outcomes. EE attenuates diabetes-associated astrocyte reactivity and glutamate dysregulation and enhances the neuroprotective effects of insulin in STZ-induced diabetic rats. These findings may support the potential role of EE as a potential non-pharmacological adjunct to insulin therapy in mitigating diabetes-related neuroinflammatory and neurochemical alterations. • STZ-induced diabetes increases astrocyte reactivity and brain glutamate levels • Environmental enrichment reduces diabetes-associated astrogliosis • Insulin therapy partially restores metabolic and neurochemical balance • Combined insulin and enrichment produce the greatest neuroprotection • Lifestyle-based enrichment shows translational potential in diabetic CNS injury