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

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

&

Liping Huang 2 & Xiaoqin Zhong 1 & Manting Huang 1

Received: 3 February 2020 / Accepted: 13 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

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, 1day 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 Vascular dementia . Autophagy . Dynamic changes

Introduction Vascular dementia (VD), a syndrome of acquired intelligence impairment and cognitive dysfunction resulted from various cerebrovascular diseases, is the second leading cause of dementia following Alzheimer’s disease (AD) (Javanshiri et al. 2018). There is a high incidence of VD in elderly people over 65 years of age, and this incidence accounts for approximately

* Liping Huang [email protected] 1

Department of Neurology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, People’s Republic of China

2

School of Chemistry and Chemical Engineering, Lingnan Normal University, No. 29, Cunjin Road, Zhanjiang 524048, People’s Republic of China

20% of all dementia cases (van Lo