Open Access

Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain

  • Authors:
    • Ge Li
    • Xiaofei He
    • Hang Li
    • Yu'e Wu
    • Yalun Guan
    • Shuhua Liu
    • Huanhuan Jia
    • Yunfeng Li
    • Lijing Wang
    • Ren Huang
    • Zhong Pei
    • Yue Lan
    • Yu Zhang
  • View Affiliations

  • Published online on: August 2, 2018     https://doi.org/10.3892/ijmm.2018.3802
  • Pages: 1935-1944
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aging is associated with impairment of the paravascular pathway caused by the activation of astrocytes and depolarization of protein aquaporin‑4 (AQP4) water channels, resulting in the accumulation of protein waste, including amyloid β (Aβ), in the brain parenchyma. The secreted glycoprotein slit guidance ligand 2 (Slit2) is important in regulating the function of the central nervous system and inflammatory response process. In the present study, 15‑month‑old Slit2 overexpression transgenic mice (Slit2‑Tg mice) and two‑photon fluorescence microscopy were used to evaluate the dynamic clearance of the paravascular pathway and the integrity of the blood‑brain barrier (BBB). The reactivity of astrocytes, polarity of AQP4 and deposition of Aβ in the brain parenchyma were analyzed by immunofluorescence. A Morris water maze test was used to examine the effect of Slit2 on spatial memory cognition in aging mice. It was found that the overexpression of Slit2 improved the clearance of the paravascular pathway by inhibiting astrocyte activation and maintaining AQP4 polarity on the astrocytic endfeet in Slit2‑Tg mice. In addition, Slit2 restored the disruption of the BBB caused by aging. The accumulation of Aβ was significantly reduced in the brain of Slit2‑Tg mice. Furthermore, the water maze experiment showed that Slit2 improved spatial memory cognition in the aging mice. These results indicated that Slit2 may have the potential to be used in the prevention and treatment of neurodegenerative diseases in the elderly.

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October 2018
Volume 42 Issue 4

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Copy and paste a formatted citation
APA
Li, G., He, X., Li, H., Wu, Y., Guan, Y., Liu, S. ... Zhang, Y. (2018). Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain. International Journal of Molecular Medicine, 42, 1935-1944. https://doi.org/10.3892/ijmm.2018.3802
MLA
Li, G., He, X., Li, H., Wu, Y., Guan, Y., Liu, S., Jia, H., Li, Y., Wang, L., Huang, R., Pei, Z., Lan, Y., Zhang, Y."Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain". International Journal of Molecular Medicine 42.4 (2018): 1935-1944.
Chicago
Li, G., He, X., Li, H., Wu, Y., Guan, Y., Liu, S., Jia, H., Li, Y., Wang, L., Huang, R., Pei, Z., Lan, Y., Zhang, Y."Overexpression of Slit2 improves function of the paravascular pathway in the aging mouse brain". International Journal of Molecular Medicine 42, no. 4 (2018): 1935-1944. https://doi.org/10.3892/ijmm.2018.3802