Degeneration in Different Parkinsonian Syndromes Relates to Astrocyte Type and Astrocyte Protein Expression

Abstract

The reactive changes in different types of astrocytes were analyzed in parkinsonian syndromes in order to identify common reactions and their relationship to disease severity. Immunohistochemistry was used on formalin-fixed, paraffin-embedded sections from the putamen, pons, and substantia nigra from 13 Parkinson disease (PD), 29 multiple-system atrophy (MSA), 34 progressive supranuclear palsy (PSP), 10 corticobasal degeneration(CBD), and 13 control cases. Classic reactive astrocytes were observed in MSA, PSP, and CBD, but not PD cases; the extent of reactivity correlated with indices of neurodegeneration and disease stage. Approximately 40% to 45% of subcortical astrocytes in PD and PSP accumulated alpha-synuclein and phospho-tau, respectively; subcortical astrocytes in MSA and CBD cases did not accumulate these proteins. Protoplasmic astrocytes were identified from fibrous astrocytes by their expression of parkin coregulated gene and apolipoprotein D, and accumulated abnormal proteins in PD, PSP, and CBD, but not MSA. The increased reactivity of parkin coregulated gene-immunoreactive protoplasmic astrocytes correlated with parkin expression in PSP and CBD. Nonreactive protoplasmic astrocytes were observed in PD and MSA cases; in PD, they accumulated alpha-synuclein, suggesting that the attenuated response might be due to an increase in the level of alpha-synuclein. These heterogeneous astroglial responses in PD, MSA, PSP, and CBD indicate distinct underlying pathogenic mechanisms in each disorder.

Astrogliopathy in Tauopathies

“…Glial fibrillary acidic protein has been reported to be absent in tufted astrocytes in PSP [58,111]. However, small amounts of GFAP are commonly redistributed around the nucleus in tufted astrocytes in PSP and FTLD-tau.…”

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

“…Astrocytes are therefore clear candidates to play an important role not only in the maintenance of dopaminergic systems in the healthy brain, but also in the brain affected by Parkinson's disease (PD), a progressive degenerative disorder primarily characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). The astroglial response is being studied deeply in PD patients and animal models of PD (Morale et al, 2006;Song et al, 2009), but we are still far from understanding it.…”

“…The homologues of ApoD in Drosophila, GLaz and NLaz, protect against oxidative damage and contribute significantly to the regulation of longevity (HullThompson et al, 2009;Ruiz et al, 2011;Sanchez et al, 2006;Walker et al, 2006). ApoD is in fact the most robust age dependent up-regulated gene in the brain, conserved across species (de Magalhaes et al, 2009;Loerch et al, 2008), and its expression is boosted by a collection of traumatic, pathological and degenerative nervous system conditions in humans (reviewed by Van Dijk et al, 2006), including Parkinson's disease (Ordonez et al, 2006;Song et al, 2009).…”

Brain edema in acute liver failure and chronic liver disease: Similarities and differences

“…These types of astrocytes are not present in rodents and their metabolic characteristics and functional role remain unknown (Oberheim et al, 2009 The pathological implications of protoplasmic and fibrous astrocytes are poorly understood. Differential sensitivity between protoplasmic and fibrous astrocytes has been described in Parkinson's disease (Song et al, 2009) and cerebral ischemia (Lukaszevicz et al, 2002). A study performed on brain tissue from patients who died with Wilson's disease demonstrated that Alzheimer type II astrocytes originate from the fibrous type of astroglia (Bertrand et al, 2001).…”