Degeneration of the centré median–parafascicular complex in Parkinson's disease

Abstract

Two major noncortical inputs to the striatum originate from the substantia nigra and the thalamic centré median-parafascicular complex. Although it is established that in Parkinson's disease there is degeneration of the nigral dopaminergic neurons, there has been little analysis of the glutamatergic centré median-parafascicular complex. We therefore evaluated these and neighboring thalamic nuclei (for specificity of any changes) in 9 Parkinson's disease patients and 8 age-matched controls. Degeneration in the substantia nigra and centré median-parafascicular complex was estimated by using quantitative neuronal counts. On average, 70% of the pigmented nigral neurons degenerated and there was 30% to 40% neuronal loss in the centré median-parafascicular complex in Parkinson's disease. Thalamic degeneration was marked in neuronal subpopulations (50% loss of parvalbumin-positive neurons in the parafascicular, and 70% loss of non-parvalbumin-positive neurons in the centré median nuclei). In contrast, adjacent thalamic nuclei did not degenerate, which supports a selective neurodegeneration of the centré median-parafascicular complex. Our results show that the thalamic centré median-parafascicular complex is an additional nondopaminergic site of neurodegeneration in Parkinson's disease. Because this thalamic region provides important sensorimotor feedback to the striatum, degeneration of this region is likely to exacerbate the clinical signs and symptoms of Parkinson's disease.

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

“…It is presentlyrecognizedthat early neuronal loss occurs in other regions involved in motor control [58,59] and in neurons of the mesocortical system [60]. The involvement of other neuronal populations takes place later in PD or only in certain clinical phenotypes and includes neuronal loss in the cholinergic basal forebrain [61], in the hypothalamic hypocretin system [62,63] and in the upper brainstem serotonin system [64].…”

Postnatal maturational properties of rat parafascicular thalamic neurons recorded in vitro

“…The identification of cell types within the intralaminar thalamus that have intrinsic membrane properties that differ from classic thalamocortical relay cells is a starting point from which to begin understanding the circuitry and function of this region in general arousal and attention. It might also help our understanding of how the loss of Pf cells in Alzheimer's (Rub et al, 2002) and Parkinson's (Henderson et al, 2000) diseases might contribute to altered thalamic function. A preliminary report of some of these findings has been published in abstract form (Phelan et al, 2002).…”

Lesion of the centromedian thalamic nucleus in MPTP‐treated monkeys

“…30 Interestingly, early observations considered the CM/Pf as a target by deep brain stimulation (DBS) for the treatment of levodopainduced dyskinesias in Parkinson's disease, [31][32][33] and this has recently been proposed in combination with DBS of the globus pallidus pars interna (GPi). 34 On the other hand, important cell loss has been described in the CM-Pf of PD patients 35 as well as in rodents after nigrostriatal damage. 25,36 To further assess the relevance of the CM/Pf as a potential therapeutic target for parkinsonism and levodopa-induced dyskinesias, we have performed chemical ablation of the caudal intralaminar nuclei in MPTP-treated monkeys and determined its impact on parkinsonian motor signs and dyskinesias.…”