Differential involvement of the periaqueductal gray in multiple system atrophy

The periaqueductal gray (PAG) consists of distinct columns that participate in the integrated control of autonomic function. We sought to determine whether the PAG is affected in multiple system atrophy (MSA), a disorder characterized by prominent autonomic failure. Brains were obtained at autopsy from 13 MSA patients (10 M, 3 F, age 61 ± 3 years) and 13 controls (8 M, 5 F, age 67 ± 4 years). Transverse formalin-fixed 50 μm sections were obtained throughout the PAG and immunostained for the vesicular transporter 2 (VGLUT-2), nitric oxide synthase (NOS), or α-synuclein and co-stained with thionin. Some sections were processed for myelin or astrocyte staining. Stereological quantitation was performed separately in the ventrolateral, lateral, dorsolateral, and dorsomedial columns of the PAG. In MSA cases, there was a decrease in the total estimated number of VGLUT-2 immunoreactive neurons in the ventrolateral, lateral, and dorsomedial and to a lesser extent dorsolateral PAG compared to controls (ventrolateral PAG: 16,299 ± 1612 vs. 27,906 ± 2480 respectively, p < 0.01; lateral PAG: 11,004 ± 1401 vs. 16,078 ± 1140 respectively, p < 0.05; and dorsomedial PAG: 8847 ± 1052 vs. 15,412 ± 1097 respectively, p < 0.001). The number of NOS immunoreactive neurons in the dorsolateral PAG was similar to controls. In all columns, the number of non-immunolabelled Nissl-stained cells was similar between groups. There was accumulation of glial cytoplasmic inclusions in all PAG columns in MSA. Our findings indicate involvement of the PAG columns in MSA, which may contribute to autonomic disturbances in this disorder.