Abstract
Vascular dementia (VaD) is the second most prevalent type of dementia characterized by progressive cognitive deficits and is a major risk factor for the development of Alzheimer's disease and other neurodegenerative disorders. This study is aimed at determining the potential neuroprotective effect of sitagliptin (STG) on cognitive deficits in L-methionine-induced VaD in rats and the possible underlying mechanisms. 30 adult male Wistar albino rats were divided equally (n = 10) into three groups: control, VaD, and VaD + STG groups. The cognitive performance of the animals was conducted by open field, elevated plus maze, Y-maze, novel object recognition, and Morris water maze tests. Serum homocysteine, TNF-α, IL-6, IL-10, total cholesterol, and triglycerides levels were assessed together with hippocampal MDA, SOD, and BDNF. Histopathological and immunohistochemical assessments of the thoracic aorta and hippocampus (CA1 region) were also performed. Chronic L-methionine administration impaired memory and learning and induced anxiety. On the other hand, STG protected against cognitive deficits through improving oxidative stress biomarkers, inflammatory mediators, lipid profiles, and hippocampus level of BDNF as well as decreasing caspase-3 and GFAP and increasing Ki-67 immunoreactions in the hippocampus. Also, STG improved the endothelial dysfunction via upregulation of aortic eNOS immunoreaction. STG improved the cognitive deficits of L-methionine-induced VaD by its antioxidant, anti-inflammatory, antiapoptotic, and neurotrophic effects. These findings suggest that STG may be a promising future agent for protection against VaD.
Highlights
Vascular dementia (VaD) is a neurodegenerative disease characterized by progressive cognitive deficits with a negative impact on patient’s quality of life
Several risk factors are associated with VaD, including cardiovascular abnormalities, dyslipidaemia, obesity, smoking, diabetes, and increased homocysteine (Hcy) level [3]; targeting these risk factors will minimize the burden
Hcy elevation was linked to changes in the structure and function of cerebral blood vessels, besides oxidative stress, both contribute to cerebral vascular dysfunction [31]
Summary
Vascular dementia (VaD) is a neurodegenerative disease characterized by progressive cognitive deficits with a negative impact on patient’s quality of life. It is considered the second most prevalent type of dementia worldwide, resulting in extensive medical and economic troubles in society [1]. Vascular dementia (VaD) is caused by cumulative hippocampal neuronal damage caused by vascular factors [2]. Several risk factors are associated with VaD, including cardiovascular abnormalities, dyslipidaemia, obesity, smoking, diabetes, and increased homocysteine (Hcy) level [3]; targeting these risk factors will minimize the burden. One of the major risk factors for VaD is hyperhomocysteinemia (HHcy) [4]. Some survey results showed that Hcy levels were significantly elevated in patients with anxiety [5]
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