Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemia

Abstract

Both nestin and the neural RNA-binding protein Musashi1 (Msi1) are expressed in neural stem cells in the subventricular zone. Neurogenesis in the hippocampus has received much attention, so we evaluated the expression of Msi1 and nestin in the adult rat hippocampus after transient forebrain ischemia. Both Msi1 and nestin were induced in the reactive astrocytes after ischemia, especially in the CA1 region, until 35 days after ischemia. Induction of both molecules suggested that reactive astrocytes might have immature characteristics. In the subgranular zone (SGZ) of the hippocampal dentate gyrus, Msi1-positive cells formed clusters after ischemia. These cells were labeled by bromodeoxyuridine (BrdU) but did not express glial fibrillary acidic protein. In contrast, very few nestin-positive cells were labeled by BrdU. Our results suggest that neuronal progenitor cells in the SGZ expressed Msi1 but not nestin. © 2002 Wiley-Liss, Inc.Key words: hippocampus; ischemia; neurogenesis; nestin; Neural stem/progenitor cells remain in the adult mammalian brain (Reynolds and Weiss, 1992;Weiss et al., 1996;Johansson et al., 1999;Doetsch et al., 1999), including human brain (Pincus et al., 1998). Neurogenesis continues throughout life in the two restricted zones, the hippocampal subgranular zone (SGZ; Das, 1965, 1967;Gould et al., 1998;Eriksson et al., 1998) and the rostral migratory stream, where newly generated immature neurons migrate from the anterior subventricular zone (SVZ) into the olfactory bulb (Lois and Alvarez-Buylla, 1994). It has been reported that brain injury stimulates neurogenesis in the SGZ and SVZ. Mechanical injury to the dentate gyrus (Gould and Tanapat, 1997), olfactory bulbectomy (Kirschenbaum et al., 1999), seizure (Parent et al., 1997), and ischemia (Liu et al., 1998;Takagi et al., 1999;Kee et al., 2001;Jin et al., 2001;Yoshimura et al., 2001) can affect cell proliferation in these neurogenic regions. Although in situ detection of neuronal progenitor cells is necessary to understand their response in vivo, no specific markers are available with which to detect progenitor cells.Both Musashi1 (Msi1) and nestin are considered selective markers for neural stem/progenitor cells. Msi1 was primarily isolated as the required molecule for asymmetric division of sensory organ precursor cells in Drosophila (Nakamura et al., 1994). Msi1 posttranscriptionally regulates numb gene expression, which is involved in Notch signaling (Imai et al., 2001). In the adult mammalian brain, Msi1 is present in the ependymal cells, subependymal cells, and astrocytes but not in the microglia, oligodendrocyte, or mature neurons (Sakakibara et al., 1996;Sakakibara and Okano, 1997;Kaneko et al., 2000). We recently demonstrated that the cluster-forming proliferative cells in the SGZ after transient forebrain ischemia and after permanent focal ischemia express Msi1 but not glial fibrillary acidic protein (GFAP; Yagita et al., 2001;Takasawa et al., 2002).Nestin was originally identified as an antigen of monoclonal antibody RAT401, whic...

Inflammation is detrimental for neurogenesis in adult brain

“…To label new cells, we used BrdUrd, a thymidine analogue that is incorporated into DNA during its synthesis, i.e., cell division, DNA replication, and to less extent DNA repair (24). Several lines of evidence strongly indicate that BrdUrd-labeled cells in the SGZ͞GCL, both in the intact brain and after insults such as cerebral ischemia and SE, are not mature neurons undergoing DNA repair but cluster-forming, dividing cells that subsequently pass through distinct neuronal differentiation steps (16,(25)(26)(27).…”

A role for the ELAV RNA-binding proteins in neural stem cells: stabilization ofMsi1mRNA

“…Regenerative events in the SVZ have already been demonstrated to occur in vivo in the adult CNS after an ischemic insult or a damage (Douen et al, 2004;Yagita et al, 2002), whereas in the hippocampus, neurogenesis has been strictly linked to the processes of learning, neuronal plasticity and memory formation (Kempermann et al, 2004;Schinder and Gage, 2004). Upregulation and cytoskeletal translocation of nELAV proteins and the subsequent positive effects on Gap43 mRNA levels have been recently described in tight association with synaptic plasticity and learning processes in rat dentate gyrus (Bolognani et al, 2004;Pascale et al, 2004;Quattrone et al, 2001).…”

Effect of canonical Wnt inhibition in the neurogenic cortex, hippocampus, and premigratory dentate gyrus progenitor pool

“…6B-BЈ). Musashi1 (Msi1) is normally expressed in progenitor cells in the hilus of newborn DG, and in a few cells in the dgm (Sakakibara et al, 1996;Kaneko et al, 2000;Yagita et al, 2002). In D6-Dkk1 mutants, Msi1 ϩ cells were hardly visible in the hilus, whereas its expression was maintained in the truncated dgm (Fig.…”