Fig. 2

Astrogliosis and differential inflammatory signature in brain regions of MBP29-hα-syn mice. A Overview of stimuli inducing upregulation of astrocytic GFAP expression. Astrocytes respond to either pathological or physiological stimuli. Alternatively, microglial subtypes or neuronal loss may result in increased astrocytic GFAP expression. Consequently, GFAP⁺ upregulated astrocytes show complex and multibranched processes [1]. Created with BioRender.com. B CNS regions analyzed of MBP29-hα-syn mice (sagittal plane). MO1/2 = Motor cortex 1/2, CC = corpus callosum, STR = striatum, SN = substantia nigra pars compacta, OB = olfactory bulb, HC = hippocampus, CB = cerebellum. C Characterization of GFAP⁺ expressing astrocytes in the cortex, the striatum, and the substantia nigra of MBP29-hα-syn mice and non-transgenic controls (NTGs). Dopaminergic neurons of the substantia nigra were visualized by tyrosine hydroxylase (TH, green; lower panel). The number of GFAP⁺ astrocytes was dramatically increased in the cortex (p < 0.001), the striatum (p < 0.001), and the substantia nigra (p < 0.001) of MBP29-hα-syn mice compared to NTGs. The numbers of GFAP⁺ astrocytes (n = 6/group/region) are shown as mean ± SD (right column); *** p < 0.001, Scale bar = 20 µm. D, E qPCR analysis of cortical and striatal microdissected tissues of MBP29-hα-syn mice and non-transgenic controls (NTGs, n = 4 animals per genotype): GFAP, VIM, and the glutamate reuptake transporters (glutamate transporter-1 (Glt-1) and the glutamate-aspartate transporter 1 (Glast)) (D) as well as pro-inflammatory cytokines such as tumor-necrosis factor α (Tnfa), interleukin-1b (Il1b), interleukin-6 (Il6), nuclear factor kappa B (Nfkb), and complement component 3 (C3) (E). Striatal expression levels of GFAP (p = 0.006) and VIM (p = 0.002) are significantly increased in MBP29-hα-syn mice, however GFAP is solely elevated in the cortex of MBP29-hα-syn mice (p = 0.001). RNA expression of GLT-1 and GLAST are not altered in both regions (D). Tnfa expression is elevated by threefold in the striatum of MBP29-hα-syn mice only (p = 0.003). In contrast, Il1b levels are similarly increased in both regions, the cortex (p = 0.0312) and the striatum (p = 0.0367) of transgenic mice. Il6 , Nfkb, and C3 expression is not altered compared to NTGs (E). Quantification (n = 4 animals/group) is shown as mean ± SD. *p < 0.05, **p < 0.01, and ***p < 0.005