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Fig. 8 | Molecular Neurodegeneration

Fig. 8

From: Transient IKK2 activation in astrocytes initiates selective non-cell-autonomous neurodegeneration

Fig. 8

Reversible downregulation of glutamate transporters and GluR1 by IKK2-CA is associated with signs of synaptic degeneration and dark cell degeneration of Purkinje cells. a Downregulation of glial glutamate transporters EAAT1/2 and the AMPA-receptor subunit GluR1 by IKK2-CA. The Purkinje cell specific glutamate transporter EAAT4 is only moderately reduced. Re-probed membranes shown also in Fig. 2j (same ERK2 loading control). b, c Repression of IKK2-CA restores expression of EAAT1, EAAT2, and GluR1. Re-probed membranes shown also in Fig. 3b (same ERK2 loading control). Representative immunoblot (b) and quantification (c). Values normalized to ERK2, shown as mean +/- s.e.m. relative to Co 12w (n = 3–4). d, e Levels of the postsynaptic density protein Prosap1 are reduced, whereas there is no major change in the presynaptic protein VGAT. Immunoblot (d) with quantification (e). mean values +/- s.e.m. relative to Co 10w, normalized to ERK2 (loading control), statistical analysis: 2-tailed unpaired t-test (n = 3–4), ns: not significant; * p < 0.05. f-g Ultrastructural analysis shows darks cell degeneration of Purkinje cells in IKK2-CA animals (age 16 weeks) with darkened cytoplasm, irregular morphology and the dilatation of Golgi cisternae (arrowheads) and endoplasmatic reticulum (arrows). Scale bars: 2 μm (upper panels), 1 μm (lower panels). g Quantification of n = 60 Purkinje cells of controls and n = 48 Purkinje cells of IKK2-CA animals (pooled of each 3 animals); statistical analysis: Fisher’s exact test, p < 0.0001

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