Dynamic Changes of Beclin-1 in the Hippocampus of Male Mice with Vascular Dementia at Different Time Points

J Mol Neurosci. 2020 Oct;70(10):1611-1618. doi: 10.1007/s12031-020-01591-y. Epub 2020 May 28.

Abstract

This study tried to investigate the dynamic changes of Beclin-1 in the hippocampus of male mice with vascular dementia (VD) at different time points. The mouse model of VD was established by the four-vessel blocking method. Then, the VD mice were randomly divided into five groups (n = 12) according to the disease duration: the 0.1-day model group, 0.5-day model group, 1-day model group, 3-day model group, 5-day model group and 14-day model group. In addition, all surgical procedures were the same in the sham group as those in the model groups, except the mice in the sham group were not subjected to clipping. The expression of Beclin-1, LC3B, p62, Bcl-2, Bax, BACE1, GFAP, MBP and ET-1 mRNA were determined by RT-PCR; the expression of Beclin-1 was detected by Western blot and immunofluorescence; the pathological characteristics of the hippocampus were observed by haematoxylin-eosin (HE) staining; and the correlation of Beclin-1 with other VD-related proteins was analysed by Pearson's correlation. Compared with that in the sham group, the expression of Beclin-1, LC3B, Bax, BACE1, GFAP, MBP and ET-1 mRNA was increased in the VD mice at different time points (0.1 day, 0.5 day, 1 day, 3 days, 5 days and 14 days) (P < 0.05) and then remained relatively stable in the 0.5-day VD mice, whereas the p62 and Bcl-2 mRNA levels decreased (P < 0.05). Beclin-1 protein expression was significantly increased in the VD mice at different time points (P < 0.05). The hippocampus showed a certain degree of neuronal damage in the VD mice at different time points (P < 0.05). Additionally, certain correlations among LC3B, p62, Bcl-2, Bax, BACE1, GFAP, MBP, ET-1 and Beclin-1 were observed in this study. In conclusion, the results described above demonstrated that neuronal damage and dynamic stability of Beclin-1 expression were established in the VD male mice after 0.5 day by the four-vessel blocking method.

Keywords: Autophagy; Dynamic changes; Vascular dementia.

MeSH terms

  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / genetics
  • Aspartic Acid Endopeptidases / metabolism
  • Beclin-1 / genetics*
  • Beclin-1 / metabolism
  • Dementia, Vascular / genetics
  • Dementia, Vascular / metabolism*
  • Endothelin-1 / genetics
  • Endothelin-1 / metabolism
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism
  • Hippocampus / metabolism*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Myelin Basic Protein / genetics
  • Myelin Basic Protein / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sequestosome-1 Protein / genetics
  • Sequestosome-1 Protein / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, mouse
  • Beclin-1
  • Becn1 protein, mouse
  • Endothelin-1
  • Glial Fibrillary Acidic Protein
  • Map1lc3b protein, mouse
  • Mbp protein, mouse
  • Microtubule-Associated Proteins
  • Myelin Basic Protein
  • Proto-Oncogene Proteins c-bcl-2
  • Sequestosome-1 Protein
  • Sqstm1 protein, mouse
  • bcl-2-Associated X Protein
  • glial fibrillary astrocytic protein, mouse
  • Bcl2 protein, mouse
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • Bace1 protein, mouse