Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local delivery of L-dopa in animals with lesions of the nigrostriatal pathway. The functional effects reported using this approach have been disappointing, probably because the striatal L-dopa levels attained have been too low. In the present study, we have defined a critical threshold level...

The attentional blink (AB)--a deficit in reporting the second of two target stimuli presented in close succession in a rapid sequence of distracters--has been related to processing limitations in working memory. Given that dopamine (DA) plays a crucial role working memory, the present study tested whether individual differences in the size of the AB can be predicted by differences in genetic pr...

The loss of dopaminergic innervation of the basal ganglia, a group of subcortical regions involved in motor control, is the hallmark of Parkinson's disease. The resulting molecular and cellular alterations mediate behavioral deficits and may modify neuronal responses to other neurotransmitters. In the present study, we sought to determine the effects of chronic dopamine (DA) depletion on respon...

OBJECTIVES The most common neurological manifestations in Wilson's disease are parkinsonism and dystonia. These are assumed to be due to striatal injury, which has been repeatedly demonstrated by pathology and CT or MRI. The substantia nigra has not been shown to be damaged in pathological studies. However, there have been clinical and imaging studies suggesting presynaptic nigrostriatal injury...

PURPOSE Parkinson's disease (PD) is a movement disorder mainly characterized by progressive neurodegeneration of dopaminergic (DAergic) neurons in the substantia nigra (SN). As yet, unknown molecular changes contribute to the development of PD leading to a great need for in vivo models that herald this disorder. Here we characterize an animal model presenting early PD pathology. METHODS Young...

Evidence from several studies suggests that the progressive degeneration of dopaminergic (DA) neurones of the substantia nigra pars compacta (SNc) in Parkinson's disease (PD) may in part be due to excessive release of glutamate from subthalamic projections onto nigral DA neurones. Previous in vitro studies have demonstrated that selective activation of Group III metabotropic glutamate receptors...

The most frequently used animal models for Parkinson's disease (PD) utilize unilateral injection of 6-hydroxydopamine (6-OHDA) in the medial forebrain bundle (MFB), which results in total denervation of the dopaminergic nigrostriatal pathway. However, neuroprotective interventions in PD require models resembling earlier stages of PD, where some dopaminergic cells and fibres remain. The aim of t...

Parkinson disease is characterized by a major loss (approximately 80% or more) of dopaminergic nigrostriatal neurons and by an increased turnover of neurotransmitter by surviving neurons of the nigrostriatal tract. In theory, increased turnover of dopamine should be associated with an oxidative stress derived from increased production of hydrogen peroxide. The peroxide is formed during the oxid...

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder in which the neostriatum degenerates early and most severely, with involvement of other brain regions. There is significant evidence that excitotoxicity may play a role in striatal degeneration through altered afferent corticostriatal and nigrostriatal projections that may modulate synaptically released stri...

Inflammation and iron accumulation in the substantia nigra (SN) are implicated in the pathogenesis of Parkinson's disease (PD). However, the relationship between neuroinflammation and iron mismanagement remain largely unknown. In the present study, an animal model induced by lipopolysaccharide (LPS) was used to evaluate iron concentration in the ventral midbrain with or without neuroinflammatio...