Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing dopaminergic alterations in diabetes with age, the goal of this study was to characterize the state of 2 critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-term hyperglycemia, specifically the nigrostriatal motor pathway and the reward-associated mesocorticolimbic pathway. Neuronal and glial alterations were evaluated 3 and 6 months after hyperglycemia induction, demonstrating preferential degeneration of the nigrostriatal pathway complemented by a noticeable astrogliosis and loss of microglial cells throughout aging. Behavioral tests confirmed the existence of motor impairments in hyperglycemic rats that resemble early parkinsonian symptomatology in rats, pensuing from nigrostriatal alterations. These results solidify the relation between hyperglycemia and nigrostriatal dopaminergic neurodegeneration, providing new insight on the higher occurrence of Parkinson's disease in diabetic patients.

Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway

Bassareo, Valentina
Membro del Collaboration Group
;
Pinna, Annalisa
Membro del Collaboration Group
;
Schlich, Michele
Membro del Collaboration Group
;
Murtas, Daniela
Membro del Collaboration Group
;
Simola, Nicola
Penultimo
Writing – Review & Editing
;
2018-01-01

Abstract

Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing dopaminergic alterations in diabetes with age, the goal of this study was to characterize the state of 2 critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-term hyperglycemia, specifically the nigrostriatal motor pathway and the reward-associated mesocorticolimbic pathway. Neuronal and glial alterations were evaluated 3 and 6 months after hyperglycemia induction, demonstrating preferential degeneration of the nigrostriatal pathway complemented by a noticeable astrogliosis and loss of microglial cells throughout aging. Behavioral tests confirmed the existence of motor impairments in hyperglycemic rats that resemble early parkinsonian symptomatology in rats, pensuing from nigrostriatal alterations. These results solidify the relation between hyperglycemia and nigrostriatal dopaminergic neurodegeneration, providing new insight on the higher occurrence of Parkinson's disease in diabetic patients.
Astrocyte; Dopamine; Dorsal striatum; Microglia; Nicotinamide-streptozotocin model; Substantia nigra pars compacta; Hyperglycemia
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/247218
Citazioni
  • ???jsp.display-item.citation.pmc??? 15
  • Scopus 27
  • ???jsp.display-item.citation.isi??? 27
social impact