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Mptp and apathy

Véronique Sgambato, Léon Tremblay
The MPTP monkey model of Parkinson's disease (PD) has allowed huge advances regarding the understanding of the pathological mechanisms of PD and L-DOPA-induced adverse effects. Among the main findings were the imbalance between the efferent striatal pathways in opposite directions between the hypokinetic and hyperkinetic states of PD. In both normal and parkinsonian monkeys, the combination of behavioral and anatomical studies has allowed the deciphering of the cortico-basal ganglia circuits involved in both movement and behavioral disorders...
March 3, 2018: Journal of Neural Transmission
Aron Baumann, Carlos G Moreira, Marta M Morawska, Sophie Masneuf, Christian R Baumann, Daniela Noain
Apathy is considered to be a core feature of Parkinson's disease (PD) and has been associated with a variety of states and symptoms of the disease, such as increased severity of motor symptoms, impaired cognition, executive dysfunction and dementia. Apart from the high prevalence of apathy in PD, which is estimated to be about 40%, the underlying pathophysiology remains poorly understood and current treatment approaches are unspecific and proved to be only partially effective. In animal models, apathy has been sub-optimally modeled, mostly by means of pharmacological and stress-induced methods, whereby concomitant depressive-like symptoms could not be ruled out...
2016: Frontiers in Human Neuroscience
LinLin Tian, Yuanxuan Xia, Hubert P Flores, Meghan C Campbell, Stephen M Moerlein, Joel S Perlmutter
Apathy commonly occurs in Parkinson disease (PD) patients; however, the role of dopamine in the pathophysiology of apathy remains elusive. We previously demonstrated that dopaminergic dysfunction within the ventral tegmental area (VTA)-nucleus accumbens (NAcc) pathway contributes to the manifestation of apathetic behaviors in monkeys treated with the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We now extend these studies to identify dopaminergic dysfunction in cortical regions that correlate with development of apathetic behaviors...
2015: PloS One
C A Brown, M C Campbell, M Karimi, S D Tabbal, S K Loftin, L L Tian, S M Moerlein, J S Perlmutter
Apathy, primarily defined as a lack of motivation, commonly occurs in people with Parkinson disease (PD). Although dysfunction of basal ganglia pathways may contribute to apathy, the role of dopamine remains largely unknown. We investigated the role of dopaminergic pathways in the manifestation of apathetic behaviors by measuring the effects of the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on monkeys' willingness to attempt goal directed behaviors, distinct from their ability to perform tasks...
July 2012: Experimental Neurology
Markus Storvik, Marie-Jeanne Arguel, Sandra Schmieder, Audrey Delerue-Audegond, Qin Li, Chuan Qin, Anne Vital, Bernard Bioulac, Christian E Gross, Garry Wong, Jean-Louis Nahon, Erwan Bezard
The presymptomatic phase of Parkinson's disease (PD) is now recognized as a prodromal phase, with compensatory mechanism masking its progression and non-motor early manifestations, such as depression, cognitive disturbances and apathy. Those mechanisms were thought to be strictly dopamine-mediated until recent advances have shed light upon involvement of putative outside-basal ganglia, i.e. cortical, structures. We took advantage of our progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaque model to monitor whole genome transcriptional changes in several brain areas...
June 2010: Neurobiology of Disease
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