The neural mechanisms and progressive nature of symptoms of Parkinson's disease—based on clinical, neurophysiological and morphological studies

Narabayashi, Hirotaro

doi:10.1007/bf02256630

Cited by 20 publications

(7 citation statements)

References 12 publications

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“…Parkinsonian symptoms are said to occur when striatal (putamenal) dopamine levels are < 20% of those of normal subjects. However, as the disease progresses in terms of dopamine cell death, there is also progressive worsening of clinical symptoms (Narabayashi, 1995; Marek et al ., 2002; Fahn, 2003; Meissner et al ., 2003). We therefore tested whether there may be sensorimotor correlates for the ∼ 40% reduction in dopamine between 6‐ and 12‐month‐old VD –/– mice.…”

Section: Discussionsupporting

confidence: 58%

Age‐related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease

Colebrooke

Humby

Lynch

et al. 2006

Eur J of Neuroscience

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Dopamine cytotoxicity is thought to contribute towards the selective loss of substantia nigra pars compacta dopamine neurons and disease progression in Parkinson's disease. However, the long-term toxicity of dopamine in vivo has not previously been established. The vesicular monoamine transporter 2 (VMAT2) sequesters monoamines into synaptic vesicles, a process that, in addition to being important in normal transmission, may also act to keep intracellular levels of monoamine neurotransmitters below potentially toxic thresholds. The homozygous VMAT2-hypomorphic mouse has an insertion in the VMAT2 gene (Slc18a2). Consequently, VMAT2-deficient mice (VD(-/-)) have an approximately 95% reduction in VMAT2 expression and an equivalent level of dopamine depletion in the striatum which results in moderate motor impairment. Here, we show that L-DOPA induces locomotor hyperactivity in VD(-/-) mice and reverses the deficit in motor coordination and balance as tested with the rotarod. We report that evidence for cytosolic accumulation of dopamine in substantia nigra neurons in these mice is two-fold: firstly, there is reduced phosphorylation of tyrosine hydroxylase at the residue associated with catechol feedback inhibition; and, secondly, there are increased rates of dopamine turnover at 6, 12 and 24 months of age. These animals exhibit a progressive decline in striatal monoamine levels and rotarod performance with increasing age. However, despite these data, there was no loss of nigral dopamine neurons as estimated by quantification of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta of old VD(-/-) mice (24-month-old), implying that these age-dependent manifestations may be due to senescence alone.

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Section: Discussionsupporting

confidence: 58%

Age‐related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease

Colebrooke

Humby

Lynch

et al. 2006

Eur J of Neuroscience

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“…In perspective, we will now discuss the disease progression. Each motor symptom participates in the progression of the disease with its own strength and timing . As noted above on the parallelism of thalamic activities and surgically removed symptoms, the β‐band activities appear to drive rigidity in timing somewhat differently from the τ‐range activities.…”

Section: Discussionmentioning

confidence: 91%

“…Each motor symptom participates in the progression of the disease with its own strength and timing. [22][23][24][25] As noted above on the parallelism of thalamic activities and surgically removed symptoms, the b-band activities appear to drive rigidity in timing somewhat differently from the srange activities. The latter acted with an apparent potency to directly drive tremor.…”

Section: Discussionmentioning

confidence: 99%

Quantitative relationships of graded motor symptoms with thalamic activities monitored during thalamotomy for a population of patients with Parkinson's disease

Narabayashi¹,

Oshima²

2015

Neurology & Clinical Neurosc

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Background: On the basis of analytical monitoring in thalamotomy for Parkinson's disease, we hypothesize that thalamic 13-27-Hz (b-band) and the 3-7-Hz (s-range) hyperactivities drive rigidity and tremor, respectively. Aim: To test the causality from these thalamic activities to symptoms, we examined quantitative relationships of rigidity, tremor and bradykinesia with the thalamic activities in 170 patients with Parkinson's disease. Methods: We classified the patients by the maximum preoperative points of unified Parkinson's disease rating scale in each of rigidity, tremor and bradykinesia; estimated their postoperative points and reductions; and measured the case-representative b-band and s-range activities (Vb, Vs) by their time integrals of thalamic local field potentials. Results: Case-by-case variability was eminent in the ages at onset and on surgery, disease duration, scores of symptoms, Vb and Vs, and their mutual relations. Yet, the relationships between the point reductions and preoperative points of rigidity and tremor were respectively positive, but non-linear because of the postoperatively spared severest part of symptoms. The preoperative points of rigidity with Vb and the preoperative points of tremor with Vs were positively related, but non-linearly, because of decreasing Vb and Vs for the highest preoperative points of rigidity and tremor, respectively. Conclusion: Riding on the case variability, Vb and Vs represented the grades of rigidity and tremor, respectively, but with non-linear parts for the severe symptoms. Pathophysiology relevant to non-linearity was at least partly attributed to other brain regions beyond the thalamus in the advanced stage of the disease.

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“…This finding of the spread of pathology within the SNc [16] seems to explain the changes in the clinical features during the progressive course of the disease. In PD patients, the first clinical sign of the disease is always a unilateral motor symptom, such as slight tremor and/or slight muscle stiffness of one extremity.…”

Section: Commentmentioning

confidence: 92%

Stereotactic Surgery and Parkinson’s Disease

Narabayashi

1998

Stereotact Funct Neurosurg

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With a short description of the historical background, thalamotomy and posteroventral pallidotomy (PVP) are introduced as effective means to alleviate motor symptoms in Parkinson’s disease (PD). Rigidity and dopa-induced dyskinesia are improved and abolished by either of the two procedures, but tremor is more markedly improved by thalamotomy than by PVP. To date, surgical treatment has been important in treating PD. Also, the influence of PVP on psychological symptoms in PD, bradyphrenia and emotional changes offers an important key to understand and to interpret these symptoms.

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The neural mechanisms and progressive nature of symptoms of Parkinson's disease—based on clinical, neurophysiological and morphological studies

Cited by 20 publications

References 12 publications

Age‐related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease

Age‐related decline in striatal dopamine content and motor performance occurs in the absence of nigral cell loss in a genetic mouse model of Parkinson's disease

Quantitative relationships of graded motor symptoms with thalamic activities monitored during thalamotomy for a population of patients with Parkinson's disease

Stereotactic Surgery and Parkinson’s Disease

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