Increased food intake, reduced physical activity and altered metabolic processes are variables affecting energy balance inducing obesity. Obesity is now considered an increasingly medical challenge associated with the development of chronic diseases. Metabolic syndrome (MetS) is another disorder related to obesity and characterized by hypertension, hyperglycemia, hypertriglyceridemia, reduced high-density lipoprotein cholesterol is accompanied by abnormal adipose deposition and function. Obesity and Mets are recognized risk factors for adult-onset dementia disorders such as Alzheimer’s disease (AD) and vascular dementia (VaD). They have been also associated with poorer cognitive performance. Moreover, combination of obesity and arterial hypertension could impair performance across various cognitive domains. The cholinergic system is altered in age-related neurodegenerative diseases, such as AD and VaD. A decline in the integrity of the cholinergic system characterized by a decrease of acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT) was also reported in patients with VaD. The present study has investigated the brain cholinergic pattern in Obese Zucker rats (OZRs) compared with controls lean Zucker rats (LZRs) at different ages. This to clarify the possible relationships between Mets, cerebral injury and cholinergic system impairment. Male OZRs and the littermate LZRs of 12, 16 and 20 weeks of age were used. The OZRs, with a mutation in leptin receptor (fa/fa), represent a model of obesity related to type 2 diabetes mellitus, that exhibiting dyslipidemia, a moderate degree of arterial hypertension. Body weight, blood pressure and blood parameters were checked. The brain was processed for immunochemical and immunohistochemical analysis of vesicular acetylcholine transporter (VAChT), ChAT, acetylcholinesterase (AChE), nicotinic(nAChRalpha7) and muscarinic(mAChR) receptor subtypes. Behavioural tests were performed to identify cognitive changes. Body weight, systolic blood pressure, glycemia, insulin, triglycerides and cholesterol levels were higher in OZRs compared to LZRs. Behavioural tests revealed in older OZRs anxiety and changes in emotional learning tasks. In frontal cortex and hippocampus of older OZRs, a decrease of VAChT and nAChRalpha7 immunoreaction was observed. Different expressions were detected in two investigated areas with a decrease of m1AChR subtype in hippocampus in 20 weeks OZRs. The modulation of the cholinergic system, in rats OZRs, is an extremely complex phenomenon and may be related both to inflammation induced by obesity and to cognitive impairment. The identification of neurodegenerative changes may represent the first step towards a better characterization of neuronal involvement in this animal model and possible treatments for countering it.

Brain cholinergic dysfunction in obese Zucker LEPR(fa/fa) rats

TOMASSONI, Daniele;TAYEBATI, Seyed Khosrow;MORUZZI, MICHELE;MARTINELLI, ILENIA;AMENTA, Francesco
2016

Abstract

Increased food intake, reduced physical activity and altered metabolic processes are variables affecting energy balance inducing obesity. Obesity is now considered an increasingly medical challenge associated with the development of chronic diseases. Metabolic syndrome (MetS) is another disorder related to obesity and characterized by hypertension, hyperglycemia, hypertriglyceridemia, reduced high-density lipoprotein cholesterol is accompanied by abnormal adipose deposition and function. Obesity and Mets are recognized risk factors for adult-onset dementia disorders such as Alzheimer’s disease (AD) and vascular dementia (VaD). They have been also associated with poorer cognitive performance. Moreover, combination of obesity and arterial hypertension could impair performance across various cognitive domains. The cholinergic system is altered in age-related neurodegenerative diseases, such as AD and VaD. A decline in the integrity of the cholinergic system characterized by a decrease of acetylcholine (ACh) biosynthetic enzyme choline acetyltransferase (ChAT) was also reported in patients with VaD. The present study has investigated the brain cholinergic pattern in Obese Zucker rats (OZRs) compared with controls lean Zucker rats (LZRs) at different ages. This to clarify the possible relationships between Mets, cerebral injury and cholinergic system impairment. Male OZRs and the littermate LZRs of 12, 16 and 20 weeks of age were used. The OZRs, with a mutation in leptin receptor (fa/fa), represent a model of obesity related to type 2 diabetes mellitus, that exhibiting dyslipidemia, a moderate degree of arterial hypertension. Body weight, blood pressure and blood parameters were checked. The brain was processed for immunochemical and immunohistochemical analysis of vesicular acetylcholine transporter (VAChT), ChAT, acetylcholinesterase (AChE), nicotinic(nAChRalpha7) and muscarinic(mAChR) receptor subtypes. Behavioural tests were performed to identify cognitive changes. Body weight, systolic blood pressure, glycemia, insulin, triglycerides and cholesterol levels were higher in OZRs compared to LZRs. Behavioural tests revealed in older OZRs anxiety and changes in emotional learning tasks. In frontal cortex and hippocampus of older OZRs, a decrease of VAChT and nAChRalpha7 immunoreaction was observed. Different expressions were detected in two investigated areas with a decrease of m1AChR subtype in hippocampus in 20 weeks OZRs. The modulation of the cholinergic system, in rats OZRs, is an extremely complex phenomenon and may be related both to inflammation induced by obesity and to cognitive impairment. The identification of neurodegenerative changes may represent the first step towards a better characterization of neuronal involvement in this animal model and possible treatments for countering it.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11581/403130
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