Effect of Obesity on Cognitive Impairment in Vascular Dementia Rat Model via BDNF-ERK-CREB Pathway

The prevalence of vascular dementia continues to increase with no cure. Thus, it is important identify the aggravating factors of vascular dementia to delay disease progression in patients. Obesity is a well-known risk factor for vascular dementia and causes mild cognitive impairment. In the present study, we evaluated whether obesity exacerbates cognitive impairment in vascular dementia rats and how it affects synaptic plasticity through the BDNF pathway. We randomly assigned 30 Wistar male rats to three groups: sham surgery (Sham), vascular dementia (VaD), and vascular dementia with obesity (OB + VaD). We fed rats a 60% high-fat diet to establish obesity; we then induced vascular dementia using bilateral common carotid artery occlusion. After 6 weeks, we evaluated cognitive function using the Morris water maze and radial arm maze tests. We analyzed post-synaptic density-95 (PSD95) and growth-associated protein-43 (GAP43) to confirm synaptic plasticity. We also evaluated brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase (pERK), and phosphorylated cyclic adenosine monophosphate response element-binding protein (pCREB) in the hippocampus. The OB + VaD group showed the most impaired cognitive function on behavioral tests, with decreases in PSD95. The VaD group showed increased levels of BDNF, pERK, and pCREB, while the OB + VaD group displayed decreased levels. We suggest that obesity exacerbates cognitive impairment in vascular dementia by inhibiting the compensatory increases of BDNF-ERK-CREB pathway.

Keywords: brain-derived neurotrophic factor; chronic cerebral hypoperfusion; high-fat diet; memory; synaptic plasticity; vascular dementia.