title: Increased expression of Slit2 and its receptors Robo1 and Robo4 in reactive astrocytes of the rat hippocampus after transient forebrain ischemia.
abstract: Slit2 is a secreted glycoprotein that was originally identified as a chemorepulsive factor in the developing brain; however, it was recently reported that Slit2 is associated with adult neuronal function including a variety of pathophysiological processes. To elucidate whether Slit2 is implicated in the pathophysiology of ischemic injury, we investigated the temporal changes and cellular localization of Slit2 and its predominant receptors, Robo1 and Robo4, for 28 days after transient forebrain ischemia. Slit2 and its receptors had similar overall expression patterns in the control and ischemic hippocampi. The ligand and receptors were constitutively expressed in hippocampal neurons in control animals; however, in animals with ischemic injury, their upregulation was detected in reactive astrocytes, but not in neurons or activated microglia, in the CA1 region. Astroglial induction of Slit2 and its receptors occurred by day 3 after reperfusion, and appeared to increase progressively until the final time point on day 28. Their temporal expression patterns overlapped with the time period in which reactive astrocytes undergo dynamic structural changes and appear hypertrophic in the ischemic hippocampus. The immunohistochemical data were consistent with the results of the immunoblot analyses, indicating that the expression of Slit2 and Robo increased progressively over the relatively long period of 28 days examined here. Collectively, these results suggest that Slit2/Robo signaling may be involved in regulating the astroglial reaction via autocrine or paracrine mechanisms in post-ischemic processes. Moreover, this may contribute to the dynamic morphological changes that occur in astrocytes in response to ischemic injury.
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 137-701 Seoul, Republic of Korea.
authors.forename: Joo-Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 137-701 Seoul, Republic of Korea.
authors.forename: Ha-Jin
authors.initials: HJ
authors.lastname: Pak
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 137-701 Seoul, Republic of Korea.
authors.forename: Tae-Ryong
authors.initials: TR
authors.lastname: Riew
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 137-701 Seoul, Republic of Korea.
authors.forename: Yoo-Jin
authors.initials: YJ
authors.lastname: Shin
authors.affiliation: Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 137-701 Seoul, Republic of Korea. Electronic address: munylee@catholic.ac.kr.
authors.forename: Mun-Yong
authors.initials: MY
authors.lastname: Lee
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D016548:Prosencephalon / Q000293:injuries*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D013997:Time Factors; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C578845:Robo4 protein, rat
keywords: Hippocampus; Ischemia; Neurons; Reactive astrocytes