Journal of Advanced Clinical Neurology Research

Abstract

Introduction: In type 2 diabetes mellitus (T2DM), there are pathophysiological mechanisms that affect the central nervous system (CNS). Diet and sedentary lifestyle are significant risk factors for the development and progression of type 2 diabetes mellitus (T2DM) and its complications, which are exacerbated by aging and alcohol consumption. Histological modifications due to diabetes mellitus have been found in central nervous system (CNS) structures in experimental models. The optic nerve (ON) provides a model for understanding DM-related CNS damage. Environmental enrichment in experimental animals, allowing them to engage in greater physical activity and neurocognitive stimulation, could aid in the treatment and recovery of various CNS-related pathologies.

Objective: To study, using transmission electron microscopy, the ultrastructure of the optic nerve in diabetic experimental animals with a high-fat diet and moderate alcohol consumption, and compare it with that of animals exposed to an enriched environment.

Materials and Methods: Thirty-six male Wistar rats, 12 months old at the start of the trial and 24 months old at the end of the study, were divided into six groups. Their metabolism was altered by a diet containing 30% saturated fats (HFD) and/or moderate alcohol consumption (0.42 g/kg body weight/day). The enriched environment (EE) group was housed in a larger cage (250 dm³) with running wheels and ramps, while the other animals were housed in standard animal facility cages (20 dm³). The trial lasted 16 months. Metabolic markers were measured, and at the end of the experiment, the animals were sacrificed. The optic nerves were extracted, fixed, and processed for electron microscopy. The data obtained were analyzed using ANOVA with a p≤0.05.

Results: The groups fed the high-fat diet (HFD) and/or alcohol became diabetic within 7 months of the trial. Dyslipidemia and increased body weight were also observed. Animals fed the enriched environment (EA) showed improved glycemic levels (118 ± 5 mg/dL) and normal weight at the end of the trial. Differences in neurocognitive tests were observed among animals under different experimental conditions. Qualitative differences in the optic nerves, such as signs of atrophy and altered mitochondrial and cristae shape, were observed in those from diabetic animals fed the HFD and/or alcohol diet compared to the control groups fed the Chow diet or the Chow diet plus enriched environment. The HFD, alcohol, HFD+Alc, and HFD+Alc+EA groups showed thickening of the myelin sheaths (between 39% and 233%) compared to the control groups (Chow and Chow+EA). In all animals on the high-fat diet (HFD), more electron-dense intracytoplasmic deposits were found. In HFD+Alc and HFD+Alc+AE, the myelin sheath showed greater separation from the axon (75% and 50% more, respectively) than in group C. In the Alc group, mitochondria were observed to be larger (119 vs. 107 nm) than in the control group.

Conclusions: The high-fat diet and sedentary lifestyle led to the development of type 2 diabetes mellitus (DM) and neurological damage in the animals. Exposure to an enriched environment partially improved the metabolic and structural alterations of the optic nerve.