ABSTRACT
Obesity is characterized by abnormal adipose tissue expansion and is associated with chronic inflammation. Obesity itself may induce several comorbidities, including psychiatric disorders. It has been previously demonstrated that proinflammatory cytokines are able to up-regulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) release, which both have a role in compulsive related behaviors. OBJECTIVE: To evaluate whether acute or chronic consumption of a high-refined carbohydrate-containing (HC) diet will modify burying-behavior in the Marble Burying Test (MBT) through augmentation of NO signaling in the striatum, a brain region related to the reward system. Further, we also verified the effects of chronic consumption of a HC diet on the reinforcing effects induced by cocaine in the Conditioned Place Preference (CPP) test. METHODS: Male BALB/c mice received a standard diet (control diet) or a HC diet for 3 days or 12 weeks. RESULTS: An increase in burying behavior occurred in the MBT after chronic consumption of a HC diet that was associated with an increase of nitrite levels in the striatum. The pre-treatment with Aminoguanidine (50â¯mg/kg), a preferential inhibitor of iNOS, prevented such alterations. Additionally, a chronic HC diet also induced a higher expression of iNOS in this region and higher glutamate release from striatal synaptosomes. Neither statistical differences were observed in the expression levels of the neuronal isoform of NOS nor in microglia number and activation. Finally, the reinforcing effects induced by cocaine (15â¯mg/kg, i.p.) during the expression of the conditioned response in the CPP test were not different between the chronically HC diet fed mice and the control group. However, HC diet-feeding mice presented impairment of cocaine-preference extinction. CONCLUSION: Altogether, our results suggest that the chronic consumption of a HC diet induces compulsive-like behavior through a mechanism possibly associated with NO activation in the striatum.
Subject(s)
Compulsive Behavior/etiology , Diet, Carbohydrate Loading/adverse effects , Nitric Oxide/metabolism , Animals , Behavior, Animal/drug effects , Cocaine/pharmacology , Conditioning, Psychological/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dietary Carbohydrates/adverse effects , Interleukin-6/metabolism , Male , Mice, Inbred BALB C , Nitric Oxide Synthase Type I/metabolism , Nitric Oxide Synthase Type II/metabolism , Potassium/metabolismABSTRACT
Neurodegenerative diseases are pathological conditions that have an insidious onset and chronic progression. Different models have been established to study these diseases in order to understand their underlying mechanisms and to investigate new therapeutic strategies. Although various in vivo models are currently in use, in vitro models might provide important insights about the pathogenesis of these disorders and represent an interesting approach for the screening of potential pharmacological agents. In the present review, we discuss various in vitro and ex vivo models of neurodegenerative disorders in mammalian cells and tissues.
Subject(s)
Alzheimer Disease/pathology , Amyotrophic Lateral Sclerosis/pathology , Culture Techniques/methods , Huntington Disease/pathology , Parkinson Disease/pathology , Alzheimer Disease/etiology , Amyotrophic Lateral Sclerosis/etiology , Animals , Astrocytes , Cells, Cultured , Disease Models, Animal , Huntington Disease/etiology , Mice , Microglia , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/pathology , Parkinson Disease/etiology , RatsABSTRACT
Neurodegenerative diseases are pathological conditions that have an insidious onset and chronic progression. Different models have been established to study these diseases in order to understand their underlying mechanisms and to investigate new therapeutic strategies. Although various in vivo models are currently in use, in vitro models might provide important insights about the pathogenesis of these disorders and represent an interesting approach for the screening of potential pharmacological agents. In the present review, we discuss various in vitro and ex vivo models of neurodegenerative disorders in mammalian cells and tissues.
