Reactive astrocytes are widespread in the cortical gray matter of amyotrophic lateral sclerosis

Abstract

The distribution of reactive astrocytes was examined in the cortical gray matter of non-motor and motor regions from cases of familial and sporadic amyotrophic lateral sclerosis (ALS) and compared to that of beta-amyloid deposits. By glial fibrillary acidic protein immunocytochemistry, patches of reactive astrocytes, characterized by multiple reactive astrocytes in a circular or patch-like formation, occurred in 12 of 15 ALS cases examined. These patches of reactive astrocytes were not restricted to the motor cortex but were found in the gray matter in ALS in all examined brain regions, including frontal, temporal, inferior parietal, cingulate, occipital, and motor cortices, from both familial and sporadic ALS cases. Reactive astrocytes were also found in the subpial region and at the gray/white matter junction. Because patches of astrocytes can occur in association with senile plaques, beta-amyloid was localized. By immunostaining, beta-amyloid deposits were observed in five of the 15 ALS cases: three cases had only early plaques, two had both early and classic plaques. The number of ALS cases with both astrocyte patches and amyloid plaques was four of 15, but typically astrocyte patches in ALS occurred without any evidence of an association with beta-amyloid deposits. Therefore, the astrocyte patches in ALS are not the result of beta-amyloid deposition. The widespread occurrence of reactive astrocytes, as patches in the cortical gray matter and in the subpial region and at the gray/white matter junction, is evidence of a widespread pathology in ALS cortex in both familial and sporadic forms of the disease.

Mesial Prefrontal Cortex Degeneration in Amyotrophic Lateral Sclerosis: A High-Field Proton MR Spectroscopy Study

“…The differences in NAA and mIns did not reach statistical significance; however, the trends were in the expected direction as decreased NAA and elevated mIns are consistent with the histologic features of neuronal loss and gliosis present in this region. 7,8,31 These trends are also similar to the pattern and magnitude of change reported in the motor cortex in ALS wherein NAA/mIns was reduced 22%, NAA/Cr was reduced 10%, and mIns/Cr was increased 18%. 19 The more pronounced abnormalities in the motor cortex would suggest a greater burden of pathology compared with the frontal lobe, consistent with the pattern of pathologic changes including the distribution of TDP-43 pathology.…”

New insights into SMA pathogenesis: immune dysfunction and neuroinflammation

“…Astrocytic activation is also present in multiple regions of the spinal cord and brain in ALS patients and mouse models,44, 46, 63 and is associated with motor neuron loss 44, 46, 64. Importantly, reduction of mSOD1 restricted to astrocytes slowed disease progression, in a similar manner as with microglial restricted mSOD1 reduction, likely attributed to inhibition of microglial activation 64.…”

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

“…In patients with ALS, astrogliosis occurs more diffusely than microgliosis, occurring in the spinal cord as well as in the gray matter and subcortical white mater [81,82]. In the G93A mSOD1 transgenic mouse, activation of astrocytes occurs concomitantly with a decrease in motor neurons [75,82,83].…”