Abstract
Neuregulin 2 reversed astrocytosis in the spinal cord in a mouse model of Alzheimer’s disease
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, P.R. China
- Center for Neuroscience, Shantou University Medical College, Shantou, Guangdong, P.R. China
- Department of Cell Biology, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, P.R. China
Introduction:
Alzheimer’s disease (AD) is classified as a neurodegenerative disorder without efficacious therapeutic interventions. Accumulating evidence has demonstrated the deposition of b-amyloid peptide (Ab) in the spinal cord in several mouse AD models. Neuregulin 2 (Nrg2), structurally homologous to neuregulin 1 (Nrg1), exerts a regulatory influence over various biological processes within the nervous system. However, the neuroprotective role of Nrg2 in the spinal cord in AD remains unclear.
Material and methods:
Reverse transcription PCR (RT-PCR) was employed to confirm the expression of mutated amyloid precursor protein (APP) in APPswe mice. Immunohistochemical staining was used to compare the differences between wild-type and APPswe mice in APP and GFAP expression. We applied western blot to test the changes of ErbB4, Akt1, and Erk1/2 activation, as well as that of GFAP in response to recombinant Nrg2 (rNrg2) treatment in the spinal cord in APPswe mice.
Results:
In the current study, we observed that mutated APP mRNA level was upregulated, and astrocytes were activated in the spinal cord of APPswe transgenic mice. rNrg2 treatment down-regulated astrocyte activation, as indicated by the reduced level of GFAP. Meanwhile, Nrg2 treatment enhanced the phosphorylation-mediated activation of ErbB4, Akt1, and Erk1/2 in most of the spinal cord segments.
Conclusions:
These combined results suggest the involvement of astrocytosis in the spinal cord of APPswe transgenic mice. Neuregulin 2, when administered exogenously, may represent a potential strategy for preventing and treating AD-induced astrocytosis in the spinal cord.
Keywords
Alzheimer’s disease (AD), APPswe transgenic mouse, spinal cord, neuregulin 2 (Nrg2), ErbB4, GFAP
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