Distinct forebrain regions define a dichotomous astrocytic profile in multiple system atrophy.

The growing recognition of a dichotomous role of astrocytes in neurodegenerative processes has heightened the need for unraveling distinct astrocytic subtypes in neurological disorders. In multiple system atrophy (MSA), a rare, rapidly progressing atypical Parkinsonian disease characterized by increased astrocyte reactivity. However the specific contribution of astrocyte subtypes to neuropathology remains elusive. Hence, we first set out to profile glial fibrillary acidic protein levels in astrocytes across the human post mortem motor cortex, putamen, and substantia nigra of MSA patients and observed an overall profound astrocytic response. Matching the post mortem human findings, a similar astrocytic phenotype was present in a transgenic MSA mouse model. Notably, MSA mice exhibited a decreased expression of the glutamate transporter 1 and glutamate aspartate transporter in the basal ganglia, but not the motor cortex. We developed an optimized astrocyte isolation protocol based on magnetic-activated cell sorting via ATPase Na+/K+ transporting subunit beta 2 and profiled the transcriptomic landscape of striatal and cortical astrocytes in transgenic MSA mice. The gene expression profile of astrocytes in the motor cortex displayed an anti-inflammatory signature with increased oligodendroglial and pro-myelinogenic expression pattern. In contrast, striatal astrocytes were defined by elevated pro-inflammatory transcripts accompanied by dysregulated genes involved in homeostatic functions for lipid and calcium metabolism. These findings provide new insights into a region-dependent, dichotomous astrocytic response-potentially beneficial in the cortex and harmful in the striatum-in MSA suggesting a differential role of astrocytes in MSA-related neurodegenerative processes.

From sweet to sweat: Hedonic olfactory range is impaired in Parkinson's disease.

INTRODUCTION: Olfactory dysfunction and neuropsychological symptoms like depression and anhedonia are common non-motor symptoms in Parkinson's disease (PD). The assessment of both functional domains includes clinical examination, olfactory testing, and standardized questionnaires. While olfaction is readily assessed by functional tests, the distinction of anhedonia as a separate symptom from other depressive symptoms is challenging. Thus, a test focusing on the assessment of hedonic olfaction may be helpful in the assessment of neuropsychological symptoms in PD. METHODS: We examined anhedonia by evaluating the perception of pleasantness of odors in PD patients (n = 57) and healthy controls (n = 46). Pleasantness of odors was registered on a visual 9-point scale. For the assessment of anhedonia we used the Snaith-Hamilton-Pleasure-Scale (SHAPS). Depression was evaluated with the Zung Self-Rating Depression Scale and the Beck Depression Inventory II. RESULTS: PD patients showed a substantial reduction in hedonic olfaction compared to controls (hedonic score: 1.5 vs. 2.2). Hyposmia, one of the most prevalent non-motor symptoms in PD, was a confounding factor. However, even normosmic PD patients showed a reduced hedonic olfaction compared to controls (hedonic score: 1.6 vs. 2.2). Furthermore, we observed a correlation between hedonic olfaction and the SHAPS-score for PD patients even though positive SHAPS-rating was observed in 9% of PD patients only, while no correlation to depression was present. CONCLUSION: These findings suggest that reduced hedonic olfaction might be an additional neuropsychological feature, probably giving insights into changes in hedonic tone complementary to hyposmia and depression in PD.