Lentiviral delivery of human erythropoietin attenuates hippocampal atrophy and improves cognition in the R6/2 mouse model of Huntington's disease

Rolfes, Simone; Munro, David A. D.; Lyras, Ekaterini Maria; Matute, Eduardo; Ouk, Koliane; Harms, Christoph; Böttcher, Chotima; Priller, Josef

doi:10.1016/j.nbd.2020.105024

Cited by 4 publications

(1 citation statement)

References 64 publications

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“…The needle was clamped and exposed to 4.5 mm, and the injection speed was 0.5 μL/min. Each side was injected with 3 μL (3 × 10 9 Exos) (Micci et al 2019 ), 3 μL of virus diluted to 1 × 10 9 TU/mL (Zhou et al 2018a , b ; Rolfes et al 2020 ), or 3 μL of atomic-NC or miR-382-3p agomir (0.8 nmol dissolved in 3 μL PBS) (Zuo et al 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Aerobic exercise improves cognitive impairment in mice with type 2 diabetes by regulating the MALAT1/miR-382-3p/BDNF signaling pathway in serum-exosomes

Wang,

Xie,

Zhao

et al. 2023

Mol Med

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Background It has been documented that aerobic exercise (AE) has a positive effect on improving cognitive function in type 2 diabetes (T2DM) patients. Here, we tried to explore how AE regulates the expression of long non-coding RNA in serum-exosomes (Exos), thereby affecting cognitive impairment in T2DM mice as well as its potential molecular mechanism. Methods T2DM mouse models were constructed, and serum-Exos were isolated for whole transcriptome sequencing to screen differentially expressed lncRNA and mRNA, followed by prediction of downstream target genes. The binding ability of miR-382-3p with a long non-coding RNA MALAT1 and brain-derived neurotrophic factor (BDNF) was explored. Then, primary mouse hippocampal neurons were collected for in vitro mechanism verification, as evidenced by the detection of hippocampal neurons' vitality, proliferation, and apoptosis capabilities, and insulin resistance. Finally, in vivo mechanism verification was performed to assess the effect of AE on insulin resistance and cognitive disorder. Results Transcriptome sequencing analysis showed that MALAT1 was lowly expressed and miR-382-3p was highly expressed in serum-Exos samples of T2DM mice. There were targeted binding sites between MALAT1 and miR-382-3p and between miR-382-3p and BDNF. In vitro experiments showed that MALAT1 upregulated BDNF expression by inhibiting miR-382-3p. Silencing MALAT1 or overexpressing miR-382-3p could reduce the expression of INSR, IRS-1, IRS-2, PI3K/AKT, and Ras/MAPK, inhibit neuronal proliferation, and promote apoptosis. In vivo experiments further confirmed that AE could increase the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thereby improving cognitive impairment in T2DM mice. Conclusion AE may upregulate the expression of MALAT1 in serum-Exos to competitively inhibit miR-382-3p and upregulate BDNF expression, thus improving cognitive impairment in T2DM mice.

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