Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy

Levy, R.; Ruberg, Merle; Herrero, M.T.; Villares, Joào; Javoy‐Agid, F.; Agid, Yves; Hirsch, Étienne C.

doi:10.1212/wnl.45.1.127

Cited by 57 publications

(33 citation statements)

References 57 publications

(4 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…55 Because PV+ GPe neurones are known to project to the output nuclei and the subthalamus, 41 a selective reduction in their inhibitory activity in association with a loss of the excitatory drive from the subthalamus would give rise to an increase in thalamic inhibition and produce parkinsonian hypokinetic symptoms, fitting well with current theories of basal ganglia pathophysiology. 11,12 Pathology in the caudate and putamen could also contribute to the hypokinetic symptoms observed in PSP.…”

Section: Discussionmentioning

confidence: 61%

See 1 more Smart Citation

The external globus pallidus in patients with Parkinson's disease and progressive supranuclear palsy

Hardman¹,

Halliday²

1999

Mov. Disord.

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 61%

“…There have been relatively few anatomic or pathologic studies of the GPe in people [53][54][55][56][57][58][59][60][61] and none analyzing changes in calcium-binding proteins. In this study, we have shown that the GPe of control subjects contains approximately 1.45 million neurones.…”

Section: Discussionmentioning

confidence: 99%

The external globus pallidus in patients with Parkinson's disease and progressive supranuclear palsy

Hardman¹,

Halliday²

1999

Mov. Disord.

View full text Add to dashboard Cite

“…The neurodegenerative changes in the striatum may result in a net loss of GABAergic neurons within the basal ganglia (Levy et al, 1995). There is a pronounced decrease in dopaminergic nerve terminals in the caudate and putamen of patients with PSP (Filippi et al, 2006), which may arise from loss of inputs from substantia nigra (Warren et al, 2007) and ventral tegmentum in the midbrain.…”

Section: Discussionmentioning

confidence: 99%

Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy

Looi

Macfarlane

Walterfang

et al. 2011

Psychiatry Research: Neuroimaging

View full text Add to dashboard Cite

Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency and dysexecutive symptoms, with some of these clinical features potentially having origins in degeneration of frontostriatal circuits and the mesencephalon. This hypothesis was investigated by manual segmentation of the caudate and putamen on MRI scans, using previously published protocols, in 15 subjects with PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the caudate and putamen was performed using spherical harmonics (SPHARM-PDM, University of North Carolina). The sagittal pons area/midbrain area ratio (P/M ratio) was significantly higher in the PSP group, consistent with previous findings. Significantly smaller striatal volumes were found in the PSP group – putamina were 10% smaller and caudate volumes were 17% smaller than in controls after controlling for age and intracranial volume. Shape analysis revealed significant shape deflation in PSP in the striatum, compared to controls; with regionally significant change relevant to frontostriatal and corticostriatal circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed cohort with early PSP, we demonstrate that neostriatal volume and shape are significantly reduced in vivo. The findings suggest a neostriatal and mesencephalic structural basis for the clinical features of PSP leading to frontostriatal and mesocortical-striatal circuit disruption.

show abstract

“…2C,D). We examined G␣olf levels in patients with another disease of basal ganglia, progressive supranuclear palsy (PSP), which shares with PD a severe dopaminergic denervation but includes degeneration of additional neuronal populations (Levy et al, 1995). An increase in G␣olf levels was also observed in the putamen of five patients with PSP, although it was less pronounced than in PD and did not reach statistical significance ( Fig.…”

Section: G␣olf Is Prominently Expressed In Human Striatummentioning

confidence: 99%

Persistent Increase in Olfactory Type G-Protein α Subunit Levels May Underlie D₁Receptor Functional Hypersensitivity in Parkinson Disease

Corvol¹,

Muriel²,

Valjent³

et al. 2004

J. Neurosci.

144

View full text Add to dashboard Cite

Although L-dopa remains the most effective treatment of Parkinson disease, its long-term administration is hampered by the appearance of dyskinesia. Hypersensitivity of dopamine D 1 receptors in the striatum has been suggested to contribute to the genesis of these delayed adverse effects. However, D 1 receptor amounts are unchanged in Parkinson disease, suggesting alterations of downstream effectors. In rodents, striatal D 1 receptors activate adenylyl cyclase through olfactory type G-protein ␣ subunit (G␣olf) and G-protein ␥ 7 subunit (G␥7). We found that G␣olf was enriched in human basal ganglia and was markedly diminished in the putamen of patients with Huntington disease, in relation with the degeneration of medium spiny neurons. In contrast, in the putamen of patients with Parkinson disease, G␣olf and G␥7 levels were both significantly increased. In the rat, the degeneration of dopamine neurons augmented G␣olf levels in the striatal neurons, specifically at the plasma membrane, an effect accounting for the increase of D 1 response on cAMP production in dopamine-depleted striatum. In lesioned rats, G␣olf levels were normalized by a 3 week treatment with L-dopa or a D 1 agonist but not with a D 2 -D 3 agonist, supporting a G␣olf regulation by D 1 receptor usage. In contrast, the increases of G␣olf levels in patients were not affected by the duration of L-dopa treatment but correlated with duration of disease. In conclusion, our results revealed in the parkinsonian putamen a prolonged elevation of G␣olf levels that may lead to a persistent D 1 receptor hypersensitivity and contribute to the genesis of long-term complications of L-dopa.

show abstract

Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy

Cited by 57 publications

References 57 publications

The external globus pallidus in patients with Parkinson's disease and progressive supranuclear palsy

The external globus pallidus in patients with Parkinson's disease and progressive supranuclear palsy

Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy

Persistent Increase in Olfactory Type G-Protein α Subunit Levels May Underlie D₁Receptor Functional Hypersensitivity in Parkinson Disease

Contact Info

Product

Resources

About

Alterations of GABAergic neurons in the basal ganglia of patients with progressive supranuclear palsy

Cited by 57 publications

References 57 publications

The external globus pallidus in patients with Parkinson's disease and progressive supranuclear palsy

The external globus pallidus in patients with Parkinson's disease and progressive supranuclear palsy

Morphometric analysis of subcortical structures in progressive supranuclear palsy: In vivo evidence of neostriatal and mesencephalic atrophy

Persistent Increase in Olfactory Type G-Protein α Subunit Levels May Underlie D1Receptor Functional Hypersensitivity in Parkinson Disease

Contact Info

Product

Resources

About

Persistent Increase in Olfactory Type G-Protein α Subunit Levels May Underlie D₁Receptor Functional Hypersensitivity in Parkinson Disease