Neuroinflammation and cognitive impairment are associated with obesity-related disorders. High-fat diets (HFD) facilitates β-amyloid accumulation, tau-protein hyperphosphorylation and inflammation which represent risk factors for adult-onset dementia disorders. The purpose of this study was to evaluate cholinergic markers, including the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) in rats with diet-induced obesity (DIO). The alpha7 nicotinic acetylcholine receptor (7nAChR), muscarinic acetylcholine receptor (mAChRs) subtypes M1, M3 and M5 were also assessed. Analysis was made in the brain of male Wistar rats after 17 weeks of HFD, starting from the 7th weeks of age. 5 weeks of HFD induced obesity. DIO rats were compared to the control rats feed with a standard diet (CHOW). The expression of cholinergic markers was investigated in the frontal cortex, hippocampus and brainstem by immunochemical and immunohistochemical techniques. Higher body weight, systolic blood pressure, glycaemia and insulin values were found in DIO rats than in CHOW. Immunohistochemistry revealed that ChAT and VAChT protein were localized primarily in frontal cortex and brainstem of obese rats. An increase in ChAT was found in different brain areas. However, reduced expression of VAChT was found in the frontal cortex of DIO rats, but not in the hippocampus. A downregulation of AChE was observed in the hippocampus and frontal cortex of DIO rats suggesting an inhibition of acetylcholine degradation. An increase of M1 and M5 receptors was observed in the hippocampus of DIO rats, whereas no differences were noticeable in M3 receptor expression. A slight decrease in the alfa7nAChR was also showed in obese phenotype. These findings suggest that HFD impairs brain cholinergic system probably related to memory functions. Changes induced by obesity to brain cholinergic system could explain the impaired learning task occurring in DIO rats.

Obesity affects the cerebral cholinergic system: evidence in high-fat diet fed rats

Martinelli I;Moruzzi M;Micioni Di Bonaventura MV;Cifani C;Amenta F;Tomassoni D.
2019

Abstract

Neuroinflammation and cognitive impairment are associated with obesity-related disorders. High-fat diets (HFD) facilitates β-amyloid accumulation, tau-protein hyperphosphorylation and inflammation which represent risk factors for adult-onset dementia disorders. The purpose of this study was to evaluate cholinergic markers, including the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), vesicular acetylcholine transporter (VAChT) and acetylcholinesterase (AChE) in rats with diet-induced obesity (DIO). The alpha7 nicotinic acetylcholine receptor (7nAChR), muscarinic acetylcholine receptor (mAChRs) subtypes M1, M3 and M5 were also assessed. Analysis was made in the brain of male Wistar rats after 17 weeks of HFD, starting from the 7th weeks of age. 5 weeks of HFD induced obesity. DIO rats were compared to the control rats feed with a standard diet (CHOW). The expression of cholinergic markers was investigated in the frontal cortex, hippocampus and brainstem by immunochemical and immunohistochemical techniques. Higher body weight, systolic blood pressure, glycaemia and insulin values were found in DIO rats than in CHOW. Immunohistochemistry revealed that ChAT and VAChT protein were localized primarily in frontal cortex and brainstem of obese rats. An increase in ChAT was found in different brain areas. However, reduced expression of VAChT was found in the frontal cortex of DIO rats, but not in the hippocampus. A downregulation of AChE was observed in the hippocampus and frontal cortex of DIO rats suggesting an inhibition of acetylcholine degradation. An increase of M1 and M5 receptors was observed in the hippocampus of DIO rats, whereas no differences were noticeable in M3 receptor expression. A slight decrease in the alfa7nAChR was also showed in obese phenotype. These findings suggest that HFD impairs brain cholinergic system probably related to memory functions. Changes induced by obesity to brain cholinergic system could explain the impaired learning task occurring in DIO rats.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/438953
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