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Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscur...

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Autores principales: Pignalosa, Francesca Chiara, Desiderio, Antonella, Mirra, Paola, Nigro, Cecilia, Perruolo, Giuseppe, Ulianich, Luca, Formisano, Pietro, Beguinot, Francesco, Miele, Claudia, Napoli, Raffaele, Fiory, Francesca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619146/
https://www.ncbi.nlm.nih.gov/pubmed/34830246
http://dx.doi.org/10.3390/ijms222212366
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author Pignalosa, Francesca Chiara
Desiderio, Antonella
Mirra, Paola
Nigro, Cecilia
Perruolo, Giuseppe
Ulianich, Luca
Formisano, Pietro
Beguinot, Francesco
Miele, Claudia
Napoli, Raffaele
Fiory, Francesca
author_facet Pignalosa, Francesca Chiara
Desiderio, Antonella
Mirra, Paola
Nigro, Cecilia
Perruolo, Giuseppe
Ulianich, Luca
Formisano, Pietro
Beguinot, Francesco
Miele, Claudia
Napoli, Raffaele
Fiory, Francesca
author_sort Pignalosa, Francesca Chiara
collection PubMed
description Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA’s role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity.
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spelling pubmed-86191462021-11-27 Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction Pignalosa, Francesca Chiara Desiderio, Antonella Mirra, Paola Nigro, Cecilia Perruolo, Giuseppe Ulianich, Luca Formisano, Pietro Beguinot, Francesco Miele, Claudia Napoli, Raffaele Fiory, Francesca Int J Mol Sci Review Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia, responsible for the onset of several long-term complications. Recent evidence suggests that cognitive dysfunction represents an emerging complication of DM, but the underlying molecular mechanisms are still obscure. Dopamine (DA), a neurotransmitter essentially known for its relevance in the regulation of behavior and movement, modulates cognitive function, too. Interestingly, alterations of the dopaminergic system have been observed in DM. This review aims to offer a comprehensive overview of the most relevant experimental results assessing DA’s role in cognitive function, highlighting the presence of dopaminergic dysfunction in DM and supporting a role for glucotoxicity in DM-associated dopaminergic dysfunction and cognitive impairment. Several studies confirm a role for DA in cognition both in animal models and in humans. Similarly, significant alterations of the dopaminergic system have been observed in animal models of experimental diabetes and in diabetic patients, too. Evidence is accumulating that advanced glycation end products (AGEs) and their precursor methylglyoxal (MGO) are associated with cognitive impairment and alterations of the dopaminergic system. Further research is needed to clarify the molecular mechanisms linking DM-associated dopaminergic dysfunction and cognitive impairment and to assess the deleterious impact of glucotoxicity. MDPI 2021-11-16 /pmc/articles/PMC8619146/ /pubmed/34830246 http://dx.doi.org/10.3390/ijms222212366 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Pignalosa, Francesca Chiara
Desiderio, Antonella
Mirra, Paola
Nigro, Cecilia
Perruolo, Giuseppe
Ulianich, Luca
Formisano, Pietro
Beguinot, Francesco
Miele, Claudia
Napoli, Raffaele
Fiory, Francesca
Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
title Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
title_full Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
title_fullStr Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
title_full_unstemmed Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
title_short Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction
title_sort diabetes and cognitive impairment: a role for glucotoxicity and dopaminergic dysfunction
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619146/
https://www.ncbi.nlm.nih.gov/pubmed/34830246
http://dx.doi.org/10.3390/ijms222212366
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