Institut de Neurosciences Cognitives et Intégratives d'Aquitaine (UMR5287)

Aquitaine Institute for Cognitive and Integrative Neuroscience



INCIA - UMR 5287- CNRS
Université de Bordeaux

Zone nord Bat 2 2ème étage
146, rue Léo Saignat
33076 Bordeaux cedex
France

Téléphone 05.57.57.15.51
Télécopie 05.56.90.14.21

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CNRS Ecole Pratique des Hautes Etudes Université de Bordeaux

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Home > Latest publications

Early neurochemical modifications of monoaminergic systems in the R6/1 mouse model of Huntington’s Disease. Neurochemistry International. 128 (2019) Emilie Puginier, Maurice Garret et Philippe De Deurwaerdère.

by Loïc Grattier - published on , updated on


Puginier et al.

Huntington’s disease (HD) is a rare, autosomal neurodegenerative disease characterized by motor and cognitive impairments appearing in adults. The R6/1 mouse model of the disease recapitulates the adult onset of motor symptoms preceded by cognitive and affective deficits. The monoaminergic systems participate in the estab- lishment of motor and cognitive loops and we postulated that their organization and interaction could be pre- cociously altered. Using tissue measurement of dopamine (DA), serotonin (5-HT), noradrenaline, and some metabolites, we observed that DA and/or its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), but not 5-HT or noradrenaline tissue content was reduced in an age-dependent manner (from two to six months) in the striatum, substantia nigra and globus pallidus of R6/1 mice. The metabolite of 5-HT was also lower in R6/1 mice, mainly in the substantia nigra and hippocampus. We then addressed early disorganization of mono- aminergic systems in 18 brain regions encompassing several neurobiological networks in 35 day-old animals. DA tissue content was not altered in the striatum or substantia nigra but was decreased in the nucleus accumbens and increased in the globus pallidus. The correlations of monoaminergic index in-between the 18 selected brain regions revealed distinct organizations of monoamines in R6/1 mice, notably marked by a loss of the number of correlations of the DOPAC/DA ratio. The neurochemical analyses show that each monoaminergic system is distinctly altered in the R6/1 mouse model. The early abnormal organization of these systems likely points out altered maturation of neurobiological networks at early stages of HD.