陆军军医大学学报 (Nov 2023)

Minocycline improves hippocampal neurogenetic defects in neonatal BTBR mice

  • LUO Yi,
  • WANG Liuyongwei,
  • ZHENG Fujie

DOI
https://doi.org/10.16016/j.2097-0927.202307136
Journal volume & issue
Vol. 45, no. 22
pp. 2299 – 2309

Abstract

Read online

Objective To investigate the effects of minocycline(Mino) treatment on hippocampal neurogenesis in early post-life BTBR T+Itpr3tf /J (BTBR) autism model mice. Methods Healthy newborn C57BL/6J (C57) and BTBR male mice were randomly divided into 4 groups: C57 saline group, C57 Mino group, BTBR saline group, and BTBR Mino group. On the postnatal day 7 (P7), the mice of the 2 Mino treatment groups were given intraperitoneal injections of Mino (22.5 mg/kg) once a day for totally 8 times, and those of the other 2 groups were given equal amounts of normal saline. In 2 h after the last injection on P14, the brain samples were collected for immunofluorescence staining to observe the expression of 5-bromo-2'-deoxyuridine(BrdU), Ki67, NeuN, DCX, SOX2, SOX2 and GFAP. Results At P14, the proliferation of BrdU and Ki67 labeled nerve cells (neural stem cells) in the hippocampus dentate gyrus was significantly decreased in the BTBR saline group than the C57 saline group (P < 0.001). While, Mino treatment resulted in obviously increased numbers of BrdU (P < 0.05) and Ki67 (P < 0.01) positive cells in the hippocampus dentate gyrus in the BTBR mice. The fluorescence intensity of DCX-positive neonatal neuronal cells was notably decreased in the hippocampal dentate gyrus of BTBR mice (P < 0.001), similar result was observed in NeuN-positive cells of mature neurons (P < 0.01), and both the intensities could be enhanced markedly by Mino treatment. Though the number of SOX2 and GFAP labeled neural stem cells was significantly lower in the BTBR saline group than the C57 saline group (P < 0.001), Mino treatment dramatically increased the number of these neural stem cells (P < 0.01). There were no statistical differences in the expression of BrdU, Ki67, NeuN, DCX, SOX2, SOX2 and GFAP in the hippocampal dentate gyrus of the mice between of the C57 saline group and the C57 Mino group, indicating that early Mino intervention had no significant effects on hippocampal neurogenesis of C57 mice. Conclusion Early postnatal Mino treatment significantly improves hippocampal neurogenesis defects in BTBR mice and promotes the proliferation of neural stem cells and neuron defferentiation in the hippocampal dentate gyrus.

Keywords