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 language | English (US) |
|---|---|
| Pages (from-to) | 106-112 |
| Number of pages | 7 |
| Journal | Neurology |
| Volume | 73 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 2009 |
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ASJC Scopus subject areas
- Clinical Neurology
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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 journal › Article
}
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 -