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

E. E. Benarroch, A. M. Schmeichel, Brittany Dugger, P. Sandroni, J. E. Parisi, P. A. Low

Research output: Contribution to journalArticle

30 Scopus citations

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 1 2009
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Benarroch, E. E., Schmeichel, A. M., Dugger, B., 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