Dataset Information

The Relevance of Insulin Action in the Dopaminergic System.

ABSTRACT: The advances in medicine, together with lifestyle modifications, led to a rising life expectancy. Unfortunately, however, aging is accompanied by an alarming boost of age-associated chronic pathologies, including neurodegenerative and metabolic diseases. Interestingly, a non-negligible interplay between alterations of glucose homeostasis and brain dysfunction has clearly emerged. In particular, epidemiological studies have pointed out a possible association between Type 2 Diabetes (T2D) and Parkinson's Disease (PD). Insulin resistance, one of the major hallmark for etiology of T2D, has a detrimental influence on PD, negatively affecting PD phenotype, accelerating its progression and worsening cognitive impairment. This review aims to provide an exhaustive analysis of the most recent evidences supporting the key role of insulin resistance in PD pathogenesis. It will focus on the relevance of insulin in the brain, working as pro-survival neurotrophic factor and as a master regulator of neuronal mitochondrial function and oxidative stress. Insulin action as a modulator of dopamine signaling and of alpha-synuclein degradation will be described in details, too. The intriguing idea that shared deregulated pathogenic pathways represent a link between PD and insulin resistance has clinical and therapeutic implications. Thus, ongoing studies about the promising healing potential of common antidiabetic drugs such as metformin, exenatide, DPP IV inhibitors, thiazolidinediones and bromocriptine, will be summarized and the rationale for their use to decelerate neurodegeneration will be critically assessed.

SUBMITTER: Fiory F

PROVIDER: S-EPMC6706784 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The Relevance of Insulin Action in the Dopaminergic System.

Fiory Francesca F Perruolo Giuseppe G Cimmino Ilaria I Cabaro Serena S Pignalosa Francesca Chiara FC Miele Claudia C Beguinot Francesco F Formisano Pietro P Oriente Francesco F

Frontiers in neuroscience 20190816

The advances in medicine, together with lifestyle modifications, led to a rising life expectancy. Unfortunately, however, aging is accompanied by an alarming boost of age-associated chronic pathologies, including neurodegenerative and metabolic diseases. Interestingly, a non-negligible interplay between alterations of glucose homeostasis and brain dysfunction has clearly emerged. In particular, epidemiological studies have pointed out a possible association between Type 2 Diabetes (T2D) and Park ...[more]

PMID: 31474827

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Project description:Many neurocognitive studies on the role of motor structures in action-language processing have implicitly adopted a "dictionary-like" framework within which lexical meaning is constructed on the basis of an invariant set of semantic features. The debate has thus been centered on the question of whether motor activation is an integral part of the lexical semantics (embodied theories) or the result of a post-lexical construction of a situation model (disembodied theories). However, research in psycholinguistics show that lexical semantic processing and context-dependent meaning construction are narrowly integrated. An understanding of the role of motor structures in action-language processing might thus be better achieved by focusing on the linguistic contexts under which such structures are recruited. Here, we therefore analyzed online modulations of grip force while subjects listened to target words embedded in different linguistic contexts. When the target word was a hand action verb and when the sentence focused on that action (John signs the contract) an early increase of grip force was observed. No comparable increase was detected when the same word occurred in a context that shifted the focus toward the agent's mental state (John wants to sign the contract). There mere presence of an action word is thus not sufficient to trigger motor activation. Moreover, when the linguistic context set up a strong expectation for a hand action, a grip force increase was observed even when the tested word was a pseudo-verb. The presence of a known action word is thus not required to trigger motor activation. Importantly, however, the same linguistic contexts that sufficed to trigger motor activation with pseudo-verbs failed to trigger motor activation when the target words were verbs with no motor action reference. Context is thus not by itself sufficient to supersede an "incompatible" word meaning. We argue that motor structure activation is part of a dynamic process that integrates the lexical meaning potential of a term and the context in the online construction of a situation model, which is a crucial process for fluent and efficient online language comprehension.

Dataset Information

The Relevance of Insulin Action in the Dopaminergic System.

Publications

The Relevance of Insulin Action in the Dopaminergic System.

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