EFFECTS OF CHOLINE-ALPHOSCERATE AND THIOCTIC ACID ON THE BRAIN OF HYPERTENSIVE RATS

Hypertension, which is caused by an elevation of blood pressure and increased arterial wall thickness, represents a risk factor for the development of cerebrovascular disease and cognitive impairment. Evidence suggests that hypertension leads to neuroinflammation, which significantly contributes to the physiopathology of cerebrovascular alterations due to the increasing production of reactive oxygen species and cholinergic pathways dysfunction. A cholinergic precursors drug, choline alphoscerate or alpha-glycerylphosphorylcholine (α-GPC), causes an increase in acetylcholine levels improving the cholinergic system countering cognitive impairment, associated with cerebrovascular damage, and could targeting neuroinflammation. (+)-Thioctic acid [(+)-TIO] is the naturally occurring eutomer that have been shown to antiinflammatory and antioxidant effects in the brain. The study was designed to investigate if treatment with the two compounds, alone or in association, could induce neuroprotection in the brain of spontaneously hypertensive rats (SHR) used as an animal model of cerebrovascular alterations. 24-weeks old SHR were treated with α-GPC (150 mg/kg/day) and (+)-TIO (125 μmol/kg/day), alone or in combination, for 4 weeks. Agematched normotensive Wistar Kyoto (WKY) rats were used as normotensive control. The frontal cortex and the hippocampus were collected for western blot and immunohistochemistry investigations of neuronal and neuroinflammatory markers. Blood pressure (BP) was higher in SHR rats compared to normotensive WKY. After 4 weeks of treatment with α-GPC and (+)-TIO, alone or in association, they reduced systolic BP while only their association reduced the diastolic BP. The immunochemical and immunohistochemical results showed that α-GPC alone restored the levels of neuronal nuclei proteins. The two compounds, alone or in association, did not prevent the downregulation of synaptophysin and microtubule-associated protein-2. α-GPC and (+)- TIO counteracted the astrogliosis, microglial activation, and decreased the level of tumor necrosis factor-alpha. Our results indicate that treating hypertensive rats with α-GPC and (+)-TIO reduced neuronal damage and glial response in the two brain areas, providing neuroprotection. The administration of the two compounds could represent a new perspective strategy to prevent hypertension-associated brain alterations. Further investigations may allow evaluating the effects on clinical trials in hypertensive patients.