Superoxide dismutase-like immunoreactivity in spheroids in Hallervorden-Spatz disease

Abstract

Iron accumulation in the basal ganglia and spheroid formation are pathological hallmarks of Hallervorden-Spatz disease (HS). Since an overaccumulation of iron (iron thesaurosis) that exceeds the binding capacity of ferritin could cause oxidative damage, we studied the possible role of oxidative stress in the pathogenesis of HS. The basal ganglia and spinal cord from patients with HS were investigated at autopsy, using histochemistry for iron and immunohistochemistry for Cu/Zn superoxide dismutase (SOD1), Mn superoxide dismutase (SOD2) and ferritin. SOD1-like immunoreactivity (IR), SOD2-IR and ferritin-IR occurred frequently in spheroids observed in the basal ganglia, and associated iron accumulation indicated the possible existence of increased oxidative stress in HS patients. Spheroids in the spinal cord showed intense SOD1-IR and SOD2-IR in HS, in sharp contrast with the occasional weak SOD1-IR and SOD2-IR observed in spheroids from patients with amyotrophic lateral sclerosis (ALS). Neither increased ferritin-IR nor iron accumulation were observed in spinal spheroids from HS and ALS patients. These data may suggest that, at least in the spinal cord, SOD1-IR and SOD2-IR in spheroids in HS patients do not result from oxidative stress directly related to iron accumulation.

Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy

“…Altered SOD expressions were identified also in child-onset neurodegenerative diseases such as Menkes' kinky hair disease [28], Hallervorden-Spatz disease [29], xeroderma pigmentosum and Cockayne syndrome [9]. In this analysis, immunoreactivity for Cu/ZnSOD was reduced in the external segment of globus pallidus and the cerebellar dentate nucleus in all DRPLA cases, regardless of the disease types.…”

Iron overload and antioxidative role of perivascular astrocytes in aceruloplasminemia

“…By contrast, the deformed astrocytes and GFSBs showed weak Cu/Zn SOD‐immunoreactivity as compared to the Mn SOD‐immunoreactivity. In Hallervorden‐Spatz disease, an iron metabolic disorder analogous to ACP, it was reported that Cu/Zn SOD‐immunoreactivity was markedly increased, while the Mn SOD‐immunoreacticity was modestly increased in the characteristic neuroaxonal swelling ‘spheroid’[21]. This suggests that different mechanisms of antioxidative system may be involved in ACP and Hallervorden‐Spats disease, although both share the common pathophysiological background of iron‐mediated oxidative stress.…”

Neurodegeneration with Brain Iron Accumulation, Type 1 Is Characterized by α-, β-, and γ-Synuclein Neuropathology

“…The major histopathological hallmarks of NBIA 1 are axonal spheroids, 3,4,11,14 which have been shown to contain immunoreactive (IR) neurofilament (NF) proteins, 7,18,19 superoxide dismutase, 11 amyloid precursor protein (APP), 20 and ␣-synuclein (␣S). 18,19,21 In addition to spheroids, other characteristic lesions include glial cytoplasmic inclusions (GCIs), 18 Lewy body (LB)-like intraneuronal inclusions (NCIs), 7,13,18,19,22 and dystrophic neurites (DNs), 7,18,19 whereas in late onset NBIA 1, tau pathology has been demonstrated 14,22,23 consisting of both paired helical filaments and straight filaments without amyloid ␤-protein (A␤) deposition.…”