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Forced limb-use effects on the behavioral and neurochemical effects of 6-hydroxydopamine
- J. Neurosci
"... Rats with unilateral depletion of striatal dopamine (DA) show marked preferential use of the ipsilateral forelimb. Previous studies have shown that implementation of motor therapy after stroke improves functional outcome (Taub et al., 1999). Thus, we have examined the impact of forced use of the imp ..."
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Cited by 19 (2 self)
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Rats with unilateral depletion of striatal dopamine (DA) show marked preferential use of the ipsilateral forelimb. Previous studies have shown that implementation of motor therapy after stroke improves functional outcome (Taub et al., 1999). Thus, we have examined the impact of forced use of the impaired forelimb during or soon after unilateral exposure to the DA neurotoxin 6-hydroxydopamine (6-OHDA). In one group of animals, the nonimpaired forelimb was immobilized using a cast, which forced exclusive use of the impaired limb for the first 7 d after infusion. The animals that received a cast displayed no detectable impairment or asymmetry of limb use, could use the contralateral (impaired) forelimb independently for vertical and lateral weight shifting, and showed no contralateral turning to apomorphine. The behavioral effects were maintained throughout the 60 d of observation. In addition to the behavioral
Learning by reviewing
- Journal of Educational Psychology
, 2011
"... © 2011 Yamauchi, Kim and Shinomoto. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are ..."
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© 2011 Yamauchi, Kim and Shinomoto. This is an open-access article subject to a non-exclusive license between the authors and Frontiers Media SA, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and other Frontiers conditions are complied with.; This Document is Protected by copyright and was first
Gene expression changes presage neurodegeneration in a Drosophila model of Parkinson’s disease
, 2003
"... model of Parkinson’s disease ..."
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Dopamine restores reward prediction errors in old age
- Nature Neuroscience
, 2013
"... Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. In a human functional magnetic resonance imaging (fMRI) study, we show that healthy older adults have an abnormal signature of expected value resulting in an incomplete reward predictio ..."
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Senescence affects the ability to utilize information about the likelihood of rewards for optimal decision-making. In a human functional magnetic resonance imaging (fMRI) study, we show that healthy older adults have an abnormal signature of expected value resulting in an incomplete reward prediction error signal in the nucleus accumbens, a brain region receiving rich input projections from substantia nigra/ventral tegmental area (SN/VTA) dopaminergic neurons. Structural connectivity between SN/VTA and striatum measured with diffusion tensor imaging (DTI) was tightly coupled to inter-individual differences in the expression of this expected reward value signal. The dopamine precursor levodopa (L-DOPA) increased the task-based learning rate and task performance in some older adults to a level shown by young adults. Critically this drug-effect was linked to restoration of a canonical neural reward prediction error. Thus we identify a neurochemical signature underlying abnormal reward processing in older adults and show this can be modulated by L-DOPA.
JV: Ageing, neurodegeneration and Parkinson’s disease
- Age Ageing
"... Age is the largest risk factor for the development and progression of Parkinson’s disease (PD). Ageing affects many cellular processes that predispose to neurodegeneration, and age-related changes in cellular function predispose to the pathogenesis of PD. The accumulation of age-related somatic dama ..."
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Age is the largest risk factor for the development and progression of Parkinson’s disease (PD). Ageing affects many cellular processes that predispose to neurodegeneration, and age-related changes in cellular function predispose to the pathogenesis of PD. The accumulation of age-related somatic damage combined with a failure of compensatory mechanisms may lead to an acceleration of PD with age. The formation of Lewy bodies may represent a marker for protective mechanisms against age-related dysfunction and degeneration of the nervous system. Mild parkinsonian signs may be present in older people, which are associated with reduced function. These may be due to age-related decline in dopaminergic activity, incidental Lewy body disease, degenerative pathologies (early PD and Alzheimer’s disease) or vascular pathology. Ageing may affect the clinical pres-entation of PD with altered drug side effects, increased risk of developing dementia and an increased likelihood of admission to a nursing home. Progression of PD, including the development of dementia, and hallucinations is related to the age of the patient rather than the age of disease onset. PD may reflect a failure of the normal cellular compensatory mechanisms in vulnerable brain regions, and this vulnerability is increased by ageing. PD is one of the best examples of an age-related disease.
Short-term GDNF treatment provides long-term rescue of lesioned nigral dopaminergic neurons in a rat model of Parkinson's disease
, 1996
"... Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenera ..."
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Glial cell line-derived neurotrophic factor (GDNF) has been shown to exert neuroprotective effects on dopamine (DA) neurons in vivo. Here we report long-term rescue of nigral DA neurons after delayed short-term GDNF administration in a rat lesion model that reproduces the slowly progressing degenerative process seen in Parkinson’s disease. GDNF injected close to the substantia nigra provided near-complete protection and persistent survival of the lesioned nigral neurons for at least 4 months after discontinuation of GDNF treatment. Long-term rescue of the nigral cells, however, was not accompanied by any significant reinnervation of the lesioned striatal target or any signs of functional recovery in either drug-induced or spontaneous motor behaviors. We conclude that not only preservation of the nigral DA neurons but also restoration of striatal DA function is necessary for functional recovery in the rat Parkinson model. Key words: GDNF; substantia nigra; striatum; neurodegeneration; behavior; Parkinson’s disease
Implicit Category Learning Performance Predicts Rate of Cognitive Decline in Nondemented Patients With Parkinson’s Disease
"... Nondemented patients with Parkinson’s disease (PD) are impaired in learning to categorize simple perceptual stimuli when category membership is defined by a nonlinear relationship between stimulus dimensions but not when the relationship is linear (J. V. Filoteo, W. T. Maddox, D. P. Salmon, & D ..."
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Nondemented patients with Parkinson’s disease (PD) are impaired in learning to categorize simple perceptual stimuli when category membership is defined by a nonlinear relationship between stimulus dimensions but not when the relationship is linear (J. V. Filoteo, W. T. Maddox, D. P. Salmon, & D. D. Song, 2005). In the present study, the authors examined whether performance in either of these 2 category learning conditions was predictive of global cognitive decline following a mean of 1.6 years since the time patients were 1st seen. Results indicated that final block accuracy in the nonlinear condition, but not the linear condition, predicted global cognitive decline. Performance on the Wisconsin Card Sorting Test (WCST) did not significantly predict global cognitive decline, although there was a trend for this to be the case. In addition, the association between nonlinear category learning and global cognitive decline
Factors affecting the clinical outcome after neural transplantation in Parkinson’s disease
"... Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson’s disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and 18 F-dopa and 11 C-raclopride ..."
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Cited by 6 (0 self)
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Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson’s disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and 18 F-dopa and 11 C-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased 18 F-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of 18 F-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas outside the grafted areas either preoperatively or at 1 or 2 years post-operatively. In contrast, patients with no or modest clinical benefit showed reduction of 18 F-dopa in ventral striatum prior to or following transplantation, which may have limited graft-induced improvement. We obtained no evidence that dyskinesias were caused by abnormal dopamine (DA) release from the grafts. As has been observed for intrinsic dopaminergic neurons, there was a significant correlation between 18 F-dopa uptake and methamphetamine-induced change of 11 C-raclopride binding (as a measure of DA release) in the putamen containing the graft. Furthermore, we
Target identification for CNS diseases by transcriptional profiling
- Neuropsychopharmacology
, 2009
"... Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human post ..."
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Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human postmortem brain, animal models, and cell culture studies. Analysis of isolated human neurons implicates targets for Alzheimer’s disease and the cognitive decline associated with normal aging and mild cognitive impairment. In addition to t, amyloid-b precursor protein, and amyloid-b peptides (Ab), these targets include all three high-affinity neurotrophin receptors and the fibroblast growth factor (FGF) system, synapse markers, glutamate receptors (GluRs) and transporters, and dopamine (DA) receptors, particularly the D2 subtype. Gene-based candidates for Parkinson’s disease (PD) include the ubiquitin–proteosome system, scavengers of reactive oxygen species, brain-derived neurotrophic factor (BDNF), its receptor, TrkB, and downstream target early growth response 1, Nurr-1, and signaling through protein kinase C and RAS pathways. Increasing variability and decreases in brain mRNA production from middle age to old age suggest that cognitive impairments during normal aging may be addressed by drugs that restore antioxidant, DNA repair, and synaptic functions including those of DA to levels of younger adults. Studies in schizophrenia identify robust decreases in genes for GABA function, including glutamic acid decarboxylase, HINT1, glutamate transport and GluRs, BDNF and TrkB, numerous 14-3-3 protein family members, and decreases in genes for CNS synaptic and metabolic functions, particularly glycolysis and ATP generation. Many of these metabolic genes are increased by insulin and muscarinic
