Abstract

Background:
Diabetic conditions are associated with altered brain functions, such as cognitive deficits, through undetermined processes like synaptic dysfunction, neurodegeneration, and biochemical imbalance. The combination of high-fat diet and streptozotocin (HFD + STZ) is a model that mimics type 2 diabetic conditions in experimental animals. This model may be useful in throwing more insight into the disease's pathology. The study aimed at investigating the short-term effect of HFD + STZ on hippocampal memory and neuronal functions and biochemical changes in the mice's brains.

Methods:
Twenty male mice (n = 10) were divided into two groups: a control group and a diabetic group (HFD + STZ). The diabetic group was fed with HFD for 28 days. Thereafter, mice in this group were induced with STZ (50 mg/kg intraperitoneally) on day 22. Weight and blood glucose levels were taken weekly. Memory functions (Y-maze and novel object recognition test (NORT)) were performed. The hippocampus (CA1) was harvested for biochemical assays such as acetylcholinesterase activity, insulin tests, cholesterol, triglycerides, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and oxidative stress (malondialdehyde, superoxide dismutase, glutathione, and myeloperoxidase) activities using enzyme-linked immunosorbent assay. Immunofluorescence and immunohistochemistry were used in determining the expressions of synaptophysin and NeuN in the brain, respectively.

Results:
Short-term administration of HFD + STZ significantly increased the weight, glucose, insulin, and acetylcholinesterase levels in the HFD + STZ-induced mice. Memory function was impaired in the HFD + STZ-induced mice. Malondialdehyde, myeloperoxidase, cholesterol, triglyceride, and LDL levels were significantly elevated, while HDL levels, superoxide dismutase, and glutathione levels were significantly reduced in the HFD + STZ-induced mice compared to the control. Synaptophysin and NeuN expressions were low in the brains of the HFD + STZ-induced mice compared to the control.

Conclusion:
Short-term administration of HFD + STZ impaired hippocampal memory functions, and the possible mechanisms could be altering neuronal activities, oxidative status, and lipid metabolism in the mice's brains.