Correlation between neuromorphometry in the substantia nigra and clinical features in Parkinson's disease using disector counts

Yong, Shuang; Röyttä, Matias; Rinne, Juha O.; Collan, Yrjö; Rinne, U. K.

doi:10.1016/s0022-510x(97)00100-7

Cited by 126 publications

(114 citation statements)

References 32 publications

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“…The results of other studies showed that motor signs of PD manifest after the loss of approximately 50% of nigral neurons and 80% of striatal dopamine [4,47]. Two postmortem studies using more rigorous quantitative methods, such as using a tessellation method [17] and dissector-based neuromorphometry [27], found that about 30% of nigral neuronal loss appeared sufficient to cause motor symptoms in PD [2]. However, recent research suggests that the first symptoms of Parkinson's disease may manifest after just a 20% decrease in the number of dopaminergic neurons SNc, which has been shown in animal models where a reduction of about 14 to 23% of nigral neuron count or 14% to 37% of striatal dopamine was sufficient to induce mild parkinsonism [43].…”

Section: Discussionmentioning

confidence: 99%

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Wójcik

Spodnik²,

Spodnik³

et al. 2014

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Section: Discussionmentioning

confidence: 99%

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Wójcik

Spodnik²,

Spodnik³

et al. 2014

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“…1 for a recent review). Although genuine longitudinal data are difficult to obtain in human material, available postmortem data indicate that the loss of DA in the caudate nucleus at the time of onset of symptoms is on the order of 70-80%, whereas as much as 70% of the nigral DA cell bodies may still be alive (1)(2)(3)(4)(5). Measurement of binding to the vesicular monoamine transporter (VMAT), which is likely to be a good measure of the functional integrity of the DA terminals, has shown severe loss of VMAT in the caudate nucleus early in the disease in some patients (6).…”

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confidence: 99%

Impaired neurotransmission caused by overexpression of α-synuclein in nigral dopamine neurons

Lundblad

Decressac

Mattsson

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

252

219

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We used in vivo amperometry to monitor changes in synaptic dopamine (DA) release in the striatum induced by overexpression of human wild-type α-synuclein in nigral DA neurons, induced by injection of an adeno-associated virus type 6 (AAV6)-α-synuclein vector unilaterally into the substantia nigra in adult rats. Impairments in DA release evolved in parallel with the development of degenerative changes in the nigrostriatal axons and terminals. The earliest change, seen 10 d after vector injection, was a marked, ≈50%, reduction in DA reuptake, consistent with an early dysfunction of the DA transporter that developed before any overt signs of axonal damage. At 3 wk, when the first signs of axonal damage were observed, the amount of DA released after a KCl pulse was reduced by 70-80%, and peak DA concentration was delayed, indicating an impaired release mechanism. At later time points, 8-16 wk, overall striatal innervation density was reduced by 60-80% and accompanied by abundant signs of axonal damage in the form of α-synuclein aggregates, axonal swellings, and dystrophic axonal profiles. At this stage DA release and reuptake were profoundly reduced, by 80-90%. The early changes in synaptic DA release induced by overexpression of human α-synuclein support the idea that early predegenerative changes in the handling of DA may initiate, and drive, a progressive degenerative process that hits the axons and terminals first. Synaptic dysfunction and axonopathy would thus be the hallmark of presymptomatic and earlystage Parkinson disease, followed by neuronal degeneration and cell loss, characteristic of more advanced stages of the disease.neurodegeneration | synaptic transmission I n Parkinson disease (PD) damage to axons and axonal terminals is likely to precede any overt dopamine (DA) neuron cell death, suggesting that the disease process may start at the axon terminal level and progress retrogradely to affect the cell bodies. Support of this idea comes from autopsy studies of brains from PD patients, which suggest that the extent of damage to the DA terminals in caudate nucleus and putamen at the time of disease onset is more extensive than the loss of DA neurons in the substantia nigra (see ref. 1 for a recent review). Although genuine longitudinal data are difficult to obtain in human material, available postmortem data indicate that the loss of DA in the caudate nucleus at the time of onset of symptoms is on the order of 70-80%, whereas as much as 70% of the nigral DA cell bodies may still be alive (1-5). Measurement of binding to the vesicular monoamine transporter (VMAT), which is likely to be a good measure of the functional integrity of the DA terminals, has shown severe loss of VMAT in the caudate nucleus early in the disease in some patients (6).Together, these data suggest that impairments at the terminal/ synaptic level may be a prominent feature of presymptomatic and early-stage PD and that impaired DA neurotransmission may contribute to the functional deficits seen also at more advanced stages of the disea...

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“…The present results have demonstrated that throughout all ages, the dopaminergic neurons in the lateral SNc are affected more severely than those in the medial SNc. In favor of these findings, it has been reported in human PD cases that the pathological change in the SNc is the most prominently observed in the ventrolateral tier [41][42][43][44]. The age-related distribution pattern of α-syn-positive neurons in the SNc is reversed.…”

Section: Discussionmentioning

confidence: 95%

Propagated but topologically distributed forebrain neurons expressing alpha-synuclein in aged macaques

Kimura

Inoue

Kuroiwa

et al. 2017

Journal of the Neurological Sciences

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In neurodegenerative disorders, such as Parkinson's disease (PD), alpha-synuclein (α-syn) accumulates to induce cell death and/or form a cytoplasmic inclusion called Lewy body (LB). This α-syn-related pathology is termed synucleinopathy. It remains unclear how α-syn accumulation expands during the progress of synucleinopathy in the human brain. In our study, we investigated the patterns of distribution and propagation of forebrain neurons expressing α-syn in aged macaques. It was found that the occurrence of α-syn-positive neurons proceeded topologically based on the midbrain dopamine pathways arising from the substantia nigra and the ventral tegmental area where they were primarily observed. In the nigrostriatal or mesolimbic dopamine pathway, the age-dependent increase in α-syn-positive neurons was evident in the striatum or the nucleus accumbens, respectively. Concerning the nigrostriatal pathway, a mediolateral or rostrocaudal gradient was seen in the substantia nigra or the striatum, respectively, and a compensatory increase in dopamine transporter occurred in the striatum regardless of the decreased dopamine level. In the mesocortical dopamine pathway, α-syn-positive neurons appeared in the prefrontal and then motor areas of the frontal lobe. Given that neither LB formation nor clinical phenotype manifestation was detected in any of the monkeys examined in the present study, aged macaques may be useful as a potential presymptomatic model for PD and LB-related neuropsychiatric disorders.

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Correlation between neuromorphometry in the substantia nigra and clinical features in Parkinson's disease using disector counts

Cited by 126 publications

References 32 publications

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Original article Nigrostriatal pathway degeneration in rats after intraperitoneal administration of proteasome inhibitor MG-132

Impaired neurotransmission caused by overexpression of α-synuclein in nigral dopamine neurons

Propagated but topologically distributed forebrain neurons expressing alpha-synuclein in aged macaques

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