Folia neuropathologica · 2025
Neuregulin 2 reversed astrocytosis in the spinal cord in a mouse model of Alzheimer's disease.
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Liu Chong, Xie Qing, Xu Jun-Ping, Hua Kai-Ye, Zhao Wei-Jiang
Аннотация
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.
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.