Neuroblast protuberances in the subventricular zone of the regenerative MRL/MpJ mouse

Abstract

The MRL mouse is unique in its capacity for regenerative healing of wounds. This regenerative ability includes complete closure, with little scarring, of wounds to the ear pinna and repair of cardiac muscle, without fibrosis, following cryoinjury. Here, we examine whether neurogenic zones within the MRL brain show enhanced regenerative capacity. The largest neurogenic zone in the adult brain, the subventricular zone (SVZ), lies adjacent to the lateral wall of the lateral ventricle and is responsible for replacement of interneuron populations within the olfactory bulb. Initial gross observation of the anterior forebrain in MRL mice revealed enlarged lateral ventricles; however, little neurodegeneration was detected within the SVZ or surrounding tissues. Instead, increased proliferation within the SVZ was observed, based on incorporation of the thymidine analogue bromodeoxyuridine. Closer examination using electron microscopy revealed that a significant number of SVZ astrocytes interpolated within the ependyma and established contact with the ventricle. In addition, subependymal, protuberant nests of cells, consisting primarily of neuroblasts, were found along the anterior SVZ of MRL mice. Whole mounts of the lateral wall of the lateral ventricle stained for the neuroblast marker doublecortin revealed normal formation of chains of migratory neuroblasts along the entire wall and introduction of enhanced green fluorescent protein-tagged retrovirus into the lateral ventricles confirmed that newly generated neuroblasts were able to track into the olfactory bulb.

Disturbed distribution of proliferative brain cells during lupus-like disease

“…The lateral ventricle walls of MRL+/+ mice contain protuberances composed primarily of neuroblasts (often marginated by astrocytes) and progenitor cells positive for DCX and BrdU markers (Baker et al, 2006). We confirmed this finding ( Fig.…”

“…Although infiltration of leukocytes into the choroid plexus has been previously documented (Alexander et al, 1983;Vogelweid et al, 1991;Farrell et al, 1997), the present data expand this finding by identifying proliferative non-T-cells. The formation of protuberances in the SVZ seems to reflect a unique regenerative capacity of peripheral organs (Clark, Clark, and Heber-Katz, 1998; Leferovich, Bedelbaeva, Samulewicz, Zhang, Zwas, Lankford, and Heber-Katz, 2001) and the brain in the MRL strain (Baker et al, 2006). However, it appears that their formation is associated with the disease onset, first in the MRL/lpr substrain and later in aged MRL+/+ mice, who start to show increased production of serum anti-nuclear antibodies (Sakic, Szechtman, Denburg, Carbotte, and Denburg, 1993).…”

Molecular guidance cues necessary for axon pathfinding from the ventral cochlear nucleus

“…Rabbit polyclonal GFAP antibody was raised against isolated full-length cow GFAP protein and is known to specifically label astrocytes (manufacturer's technical information). This GFAP antibody detects a single 50 -53 kDa polypeptide band by Western blot (Toma et al, 2001;Baker et al, 2006). Primary antibody was omitted in control samples; no immunoreactivity was detected in these samples.…”

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

“…Since that time, there have been many reports showing that multiple tissue types in MRL mice display healing responses. These include heart myocardium (Leferovich et al, 2001;Haris Naseem et al, 2007;Alfaro et al, 2008), digits (Chadwick et al, 2007;Gourevitch et al, 2009), articular cartilage (Fitzgerald et al, 2008;Rai et al, 2012), intra-articular fractures (Ward et al, 2008), corneal epithelium (Ueno et al, 2005), CNS stem cells and tissue (Hampton et al, 2004;Baker et al, 2006;Balu et al, 2009;Thuret et al, 2009), central and peripheral nerves (Buckley et al, 2011;Thuret et al, 2012) and myometrial healing (Buhimschi et al, 2010). Further, dorsal skin wounds repaired with skin transplants also show enhanced healing without scarring in MRL (Tolba et al, 2010).…”