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 (MS) a disorder characterized by prominent autonomic failure Brains were obtained at autopsy from 13 MSA patients (10 M 3 F age 6 +/- 3 years) and 13 controls (8 M 5 F age 67 +/- 4 years) Transverse formalin-fixed 50 pm sections were obtained throughout the FAG and immunostained for the vesicular transporter 2 (VGLUT-2) nitric oxide synthase (NOS) or alpha-synuclein and co-stained with thionin Some sections wire 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 PAC compared to controls (ventrolateral PAC 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 3847 +/- 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 Nis I-stained cells was similar between groups There was accumulation of ghat 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 (C) 2010 Elsevier B V All rights reserved