Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia

E. E. Benarroch, A. M. Schmeichel, B. N. Dugger, P. Sandroni, Joseph E Parisi, Phillip Anson Low

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

BACKGROUND: Experimental studies indicate that dopaminergic neurons in the ventral periaqueductal gray matter (PAG) are involved in maintenance of wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement of these neurons has not yet been explored. METHODS: We sought to determine whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB. We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female, age 61 ± 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1 female, age 79 ± 4) with diagnosis of DLB and limbic or neocortical Lewy body disease, and 12 controls (7 male, 5 female, ages 67 ± 4). Fifty-micron sections were immunostained for tyrosine hydroxylase (TH) or α-synuclein and costained with thionin. Cell counts were performed every 400 μm throughout the ventral PAG using stereologic techniques. RESULTS: Compared to the total estimated cell numbers in controls (21,488 ± 8,324 cells), there was marked loss of TH neurons in the ventral PAG in both MSA (11,727 ± 5,984; p < 0.01) and DLB (5,163 ± 1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were characteristic α-synuclein inclusions in the ventral PAG in both MSA and DLB. CONCLUSIONS: There is loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons in both multiple system atrophy and dementia with Lewy bodies, which may contribute to excessive daytime sleepiness in these conditions.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalNeurology
Volume73
Issue number2
DOIs
StatePublished - Jul 2009

Fingerprint

Multiple System Atrophy
Lewy Body Disease
Periaqueductal Gray
Dopamine
Dopaminergic Neurons
Synucleins
Tyrosine 3-Monooxygenase
Thionins
Cell Count
Neurons
Wakefulness
Mesencephalon
Autopsy
Maintenance

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Benarroch, E. E., Schmeichel, A. M., Dugger, B. N., Sandroni, P., Parisi, J. E., & Low, P. A. (2009). Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia. Neurology, 73(2), 106-112. https://doi.org/10.1212/WNL.0b013e3181ad53e7

Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia. / Benarroch, E. E.; Schmeichel, A. M.; Dugger, B. N.; Sandroni, P.; Parisi, Joseph E; Low, Phillip Anson.

In: Neurology, Vol. 73, No. 2, 07.2009, p. 106-112.

Research output: Contribution to journalArticle

Benarroch, EE, Schmeichel, AM, Dugger, BN, Sandroni, P, Parisi, JE & Low, PA 2009, 'Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia', Neurology, vol. 73, no. 2, pp. 106-112. https://doi.org/10.1212/WNL.0b013e3181ad53e7
Benarroch, E. E. ; Schmeichel, A. M. ; Dugger, B. N. ; Sandroni, P. ; Parisi, Joseph E ; Low, Phillip Anson. / Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia. In: Neurology. 2009 ; Vol. 73, No. 2. pp. 106-112.
@article{fad955f883454f9d8dc78443ec7bae10,
title = "Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia",
abstract = "BACKGROUND: Experimental studies indicate that dopaminergic neurons in the ventral periaqueductal gray matter (PAG) are involved in maintenance of wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement of these neurons has not yet been explored. METHODS: We sought to determine whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB. We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female, age 61 ± 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1 female, age 79 ± 4) with diagnosis of DLB and limbic or neocortical Lewy body disease, and 12 controls (7 male, 5 female, ages 67 ± 4). Fifty-micron sections were immunostained for tyrosine hydroxylase (TH) or α-synuclein and costained with thionin. Cell counts were performed every 400 μm throughout the ventral PAG using stereologic techniques. RESULTS: Compared to the total estimated cell numbers in controls (21,488 ± 8,324 cells), there was marked loss of TH neurons in the ventral PAG in both MSA (11,727 ± 5,984; p < 0.01) and DLB (5,163 ± 1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were characteristic α-synuclein inclusions in the ventral PAG in both MSA and DLB. CONCLUSIONS: There is loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons in both multiple system atrophy and dementia with Lewy bodies, which may contribute to excessive daytime sleepiness in these conditions.",
author = "Benarroch, {E. E.} and Schmeichel, {A. M.} and Dugger, {B. N.} and P. Sandroni and Parisi, {Joseph E} and Low, {Phillip Anson}",
year = "2009",
month = "7",
doi = "10.1212/WNL.0b013e3181ad53e7",
language = "English (US)",
volume = "73",
pages = "106--112",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Dopamine cell loss in the periaqueductal gray in multiple system atrophy and Lewy body dementia

AU - Benarroch, E. E.

AU - Schmeichel, A. M.

AU - Dugger, B. N.

AU - Sandroni, P.

AU - Parisi, Joseph E

AU - Low, Phillip Anson

PY - 2009/7

Y1 - 2009/7

N2 - BACKGROUND: Experimental studies indicate that dopaminergic neurons in the ventral periaqueductal gray matter (PAG) are involved in maintenance of wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement of these neurons has not yet been explored. METHODS: We sought to determine whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB. We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female, age 61 ± 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1 female, age 79 ± 4) with diagnosis of DLB and limbic or neocortical Lewy body disease, and 12 controls (7 male, 5 female, ages 67 ± 4). Fifty-micron sections were immunostained for tyrosine hydroxylase (TH) or α-synuclein and costained with thionin. Cell counts were performed every 400 μm throughout the ventral PAG using stereologic techniques. RESULTS: Compared to the total estimated cell numbers in controls (21,488 ± 8,324 cells), there was marked loss of TH neurons in the ventral PAG in both MSA (11,727 ± 5,984; p < 0.01) and DLB (5,163 ± 1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were characteristic α-synuclein inclusions in the ventral PAG in both MSA and DLB. CONCLUSIONS: There is loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons in both multiple system atrophy and dementia with Lewy bodies, which may contribute to excessive daytime sleepiness in these conditions.

AB - BACKGROUND: Experimental studies indicate that dopaminergic neurons in the ventral periaqueductal gray matter (PAG) are involved in maintenance of wakefulness. Excessive daytime sleepiness (EDS) is a common manifestation of multiple system atrophy (MSA) and dementia with Lewy bodies (DLB) but involvement of these neurons has not yet been explored. METHODS: We sought to determine whether there is loss of dopaminergic neurons in the ventral PAG in MSA and DLB. We studied the midbrain obtained at autopsy from 12 patients (9 male, 3 female, age 61 ± 3) with neuropathologically confirmed MSA, 12 patients (11 male, 1 female, age 79 ± 4) with diagnosis of DLB and limbic or neocortical Lewy body disease, and 12 controls (7 male, 5 female, ages 67 ± 4). Fifty-micron sections were immunostained for tyrosine hydroxylase (TH) or α-synuclein and costained with thionin. Cell counts were performed every 400 μm throughout the ventral PAG using stereologic techniques. RESULTS: Compared to the total estimated cell numbers in controls (21,488 ± 8,324 cells), there was marked loss of TH neurons in the ventral PAG in both MSA (11,727 ± 5,984; p < 0.01) and DLB (5,163 ± 1,926; p < 0.001) cases. Cell loss was more marked in DLB than in MSA. There were characteristic α-synuclein inclusions in the ventral PAG in both MSA and DLB. CONCLUSIONS: There is loss of putative wake-active ventral periaqueductal gray matter dopaminergic neurons in both multiple system atrophy and dementia with Lewy bodies, which may contribute to excessive daytime sleepiness in these conditions.

UR - http://www.scopus.com/inward/record.url?scp=68149152781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68149152781&partnerID=8YFLogxK

U2 - 10.1212/WNL.0b013e3181ad53e7

DO - 10.1212/WNL.0b013e3181ad53e7

M3 - Article

C2 - 19597132

AN - SCOPUS:68149152781

VL - 73

SP - 106

EP - 112

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 2

ER -