engleski

Expression of the neuron-specific neuroplastin isoform is altered in the 5xFAD mouse model of Alzheimer's disease

We aimed to determine whether the expression of a neuron-specific isoform of the transmembrane glycoprotein neuroplastin-65 (Np65) is altered in brains of 5xFAD mice, a murine model of familial Alzheimer’s disease. As Np is known to act as an auxiliary subunit of plasma membrane calcium ATP- ase (PMCA), crucial for cytosolic Ca2+ homeostasis, we additionally analyzed PMCA expression in brains of 5xFAD mice. We used cortices, hippocampi and cerebella from 5xFAD mice divided in groups with early and late neurodegenerative changes, in comparison to age-/gender-matched wild-type (WT) mice. The expression of Np65 and PMCA was analyzed by Western blotting and their tissue distribution by immunohistochemistry and immunofluorescence. In aged 5xFAD mice (10-15 months old) compared to WT, we found decreased hippocampal and cortical Np65 expression in homogenates and tissue sections. Additionally, we report a decrease in Np65 immunoreactivity with increasing age in both WT and 5xFAD mice. PMCA immunoreactivity in hippocampal and cortical sections expectedly showed a similar pattern as Np65, being decreased in 5xFAD animals compared to WT. No difference in the expression of neuroplastin was observed in cerebella of 5xFAD vs WT. Previously, we reported increased Np65 expression in human hippocampi affected by sporadic Alzheimer’s disease (sAD). Here, we show decreased hippocampal and cortical Np65 immunoreactivity in aged 5xFAD mice, which may be explained by different underlying pathogenesis in FAD and sAD. We suggest there is strong evidence that Np is one of the key-players affected in AD pathology.

neurodegeneration ; PMCA

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