Neuregulin 2 reversed astrocytosis in the spinal cord in a mouse model of Alzheimer's disease.

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.