Early neurochemical modifications of monoaminergic systems in the R6/1 mouse model of Huntington’s disease
Neurochemistry International. 2019-09-01; 128: 186-195
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Puginier E(1), Bharatiya R(2), Chagraoui A(3), Manem J(1), Cho YH(1), Garret M(1), De Deurwaerdère P(4).
(1)Centre National de La Recherche Scientifique-Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France.
(2)Centre National de La Recherche Scientifique-Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France; Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, SS 554, Km 4,500, 09042, Monserrato, Cagliari, Italy.
(3)Normandie Univ, UNIROUEN, INSERM, U1239, CHU Rouen, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Institute for Research and Innovation in Biomedicine of Normandy (IRIB), Department of Medical Biochemistry, Rouen University Hospital, Rouen, France.
(4)Centre National de La Recherche Scientifique-Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France. Electronic address: .
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 establishment of motor and cognitive loops and we postulated
that their organization and interaction could be precociously 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 monoaminergic 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.