TY - JOUR
T1 - Maternal stress programs accelerated aging of the basal ganglia motor system in offspring
AU - Marrocco, Jordan
AU - Verhaeghe, Remy
AU - Bucci, Domenico
AU - Di Menna, Luisa
AU - Traficante, Anna
AU - Bouwalerh, Hammou
AU - Van Camp, Gilles
AU - Ghiglieri, Veronica
AU - Picconi, Barbara
AU - Calabresi, Paolo
AU - Ravasi, Laura
AU - Cisani, Francesca
AU - Bagheri, Farzaneh
AU - Pittaluga, Anna
AU - Bruno, Valeria
AU - Battaglia, Giuseppe
AU - Morley-Fletcher, Sara
AU - Nicoletti, Ferdinando
AU - Maccari, Stefania
N1 - Funding Information:
This study was supported by the Framework of the Prenatal Stress and Neurodegenerative Diseases International Associated Laboratory (LIA-PSND) co-directed by Professors S. Maccari and F. Nicoletti between the University of Lille/CNRS, FRANCE and Sapienza University of Rome/NEUROMED-IRRCS, ITALY.
Publisher Copyright:
© 2020 The Authors
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/11
Y1 - 2020/11
N2 - Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adult (4 months of age) and old (21 months of age) male rats. Adult PRS offspring rats showed reduced dopamine (DA) release in the striatum associated with reductions in tyrosine hydroxylase-positive (TH+) cells and DA transporter (DAT) levels, with no loss of striatal dopaminergic terminals as assessed by positron emission tomography analysis with fluorine-18-l-dihydroxyphenylalanine. Striatal levels of DA and its metabolites were increased in PRS rats. In contrast, D2 DA receptor signaling was reduced and A2A adenosine receptor signaling was increased in the striatum of adult PRS rats. This indicated enhanced activity of the indirect pathway of the basal ganglia motor circuit. Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. The aged PRS rats also showed a persistent reduction in striatal DA release and defective motor skills in the pasta matrix and ladder rung walking tests. In addition, the old rats showed large increases in the levels of SNAP-25 and synaptophysin, which are synaptic vesicle-related proteins in the striatum, and in the PRS group only, reductions in Syntaxin-1 and Rab3a protein levels were observed. Our findings indicated that the age-dependent threshold for motor dysfunction was lowered in PRS rats. This area of research is underdeveloped, and our study suggests that early-life stress can contribute to an increased understanding of how aging diseases are programmed in early-life.
AB - Early-life stress involved in the programming of stress-related illnesses can have a toxic influence on the functioning of the nigrostriatal motor system during aging. We examined the effects of perinatal stress (PRS) on the neurochemical, electrophysiological, histological, neuroimaging, and behavioral correlates of striatal motor function in adult (4 months of age) and old (21 months of age) male rats. Adult PRS offspring rats showed reduced dopamine (DA) release in the striatum associated with reductions in tyrosine hydroxylase-positive (TH+) cells and DA transporter (DAT) levels, with no loss of striatal dopaminergic terminals as assessed by positron emission tomography analysis with fluorine-18-l-dihydroxyphenylalanine. Striatal levels of DA and its metabolites were increased in PRS rats. In contrast, D2 DA receptor signaling was reduced and A2A adenosine receptor signaling was increased in the striatum of adult PRS rats. This indicated enhanced activity of the indirect pathway of the basal ganglia motor circuit. Adult PRS rats also showed poorer performance in the grip strength test and motor learning tasks. The aged PRS rats also showed a persistent reduction in striatal DA release and defective motor skills in the pasta matrix and ladder rung walking tests. In addition, the old rats showed large increases in the levels of SNAP-25 and synaptophysin, which are synaptic vesicle-related proteins in the striatum, and in the PRS group only, reductions in Syntaxin-1 and Rab3a protein levels were observed. Our findings indicated that the age-dependent threshold for motor dysfunction was lowered in PRS rats. This area of research is underdeveloped, and our study suggests that early-life stress can contribute to an increased understanding of how aging diseases are programmed in early-life.
KW - Adenosine receptors
KW - Aging
KW - Integrated study
KW - Motor behavior
KW - Nigrostriatal development
KW - Synaptic proteins
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U2 - 10.1016/j.ynstr.2020.100265
DO - 10.1016/j.ynstr.2020.100265
M3 - Article
AN - SCOPUS:85097088447
VL - 13
JO - Neurobiology of Stress
JF - Neurobiology of Stress
SN - 2352-2895
M1 - 100265
ER -