TY - JOUR
T1 - Gut–brain and brain–gut axis in Parkinson's disease models
T2 - Effects of a uridine and fish oil diet
AU - Perez-Pardo, P.
AU - Dodiya, H.B.
AU - Broersen, L.M.
AU - Douna, H.
AU - van Wijk, N.
AU - Lopes da Silva, S.
AU - Garssen, J.
AU - Keshavarzian, A.
AU - Kraneveld, A.D.
PY - 2018/7/3
Y1 - 2018/7/3
N2 - © 2017, © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The ‘dual-hit’ hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this ‘dual-hit hypothesis’ and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models. Mice were given rotenone either orally or by an injection in the striatum. Dietary interventions were started 1 week before rotenone exposures. We found that (1) both oral and intrastriatal administration of rotenone induced similar PD-like motor deficits, dopaminergic cell loss, delayed intestinal transit, inflammation, and alpha-synuclein accumulation in the colon; (2) the uridine and DHA containing diet prevented rotenone-induced motor and GI dysfunctions in both models. The models suggest possible bidirectional communication between the gut and the brain for the genesis of PD-like phenotype and pathology. The dietary intervention may provide benefits in the prevention of motor and non-motor symptoms in PD.
AB - © 2017, © 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The ‘dual-hit’ hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this ‘dual-hit hypothesis’ and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models. Mice were given rotenone either orally or by an injection in the striatum. Dietary interventions were started 1 week before rotenone exposures. We found that (1) both oral and intrastriatal administration of rotenone induced similar PD-like motor deficits, dopaminergic cell loss, delayed intestinal transit, inflammation, and alpha-synuclein accumulation in the colon; (2) the uridine and DHA containing diet prevented rotenone-induced motor and GI dysfunctions in both models. The models suggest possible bidirectional communication between the gut and the brain for the genesis of PD-like phenotype and pathology. The dietary intervention may provide benefits in the prevention of motor and non-motor symptoms in PD.
UR - http://www.scopus.com/inward/record.url?scp=85014657418&partnerID=8YFLogxK
U2 - 10.1080/1028415X.2017.1294555
DO - 10.1080/1028415X.2017.1294555
M3 - Article
SN - 1028-415X
VL - 21
SP - 391
EP - 402
JO - Nutritional Neuroscience
JF - Nutritional Neuroscience
IS - 6
ER -