Proliferation and phenotype regulation in the subventricular zone during experimental allergic encephalomyelitis: In vivo evidence of a role for nerve growth factor

Abstract

Proliferating cells in the subventricular zone (SVZ) of adult rat brain could provide a source of cells for repair attempts during degenerative diseases. However, very few reports dealt with the spontaneous regulation of this cell population during experimental conditions. In this paper, we describe an increase in the proliferation activity in the SVZ during experimental allergic encephalomyelitis, a demyelinating disease widely used as an experimental model for human multiple sclerosis. Moreover, p75 LNGFR -immunoreactive elements in the SVZ were larger in experimental allergic encephalomyelitis compared with control groups, and they also showed multiple and branched elongations. Finally, a selective uptake of 125 I-nerve growth factor was observed in the SVZ in neonatal rats, and positive elements migrated in the corpus callosum within a few days. These data indicate that cell populations in the SVZ are regulated during inf lammatory conditions and degenerative diseases involving oligodendrocytes and neurotrophins, including nerve growth factor, could participate in these phenomena.The repair capability of the nervous system is extremely low in adult life, in view of the postmitotic nature of neural and glial elements. This at least partially accounts for the devastating consequences of acute damage (i.e., stroke, trauma, etc.) and long-lasting neurodegenerative processes (i.e., Alzheimer's disease, Parkinson's disease, multiple sclerosis, etc.). Experimental allergic encephalomyelitis (EAE) and multiple sclerosis are degenerative diseases characterized by the severe loss of oligodendrocytes and consequent demyelination, probably caused by inflammatory and autoimmune components. We previously have reported that nerve growth factor (NGF) increases in the cerebrospinal fluid of patients affected by multiple sclerosis (1) and also in brain areas of rats during EAE (2), where p75 LNGFR immunoreactivity also is strongly upregulated according to the severity of inflammatory cellular infiltrate (2). These and other data suggest a functional relation between the NGF level, p75 LNGFR regulation, and the stage of the disease. In these conditions, NGF and related neurotrophins, such as other growth factors, are believed to play a major role in protection such as repair attempts. However, effective strategies to transfer successful experimental approaches aiming at manipulating endogenous levels of neurotrophins to stimulate protective and repair phenomena in humans are not still available.The recent discovery of multipotent dividing, epidermal growth factor-sensitive cells in the subventricular zone (SVZ) of the mature central nervous system (CNS) in rodents and also in humans has offered a new potentiality for brain repair strategies. This large population of rapidly and constitutively proliferating cells gives rise not only to periglomerular neurons and interneurons in the olfactory bulb, but also to glial cells including oligodendrocytes (3, 4). In vivo (5) and in vitro (6) studies have indicated that growth f...

Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease

“…To perform this investigation, we injected BrdUrd during the acute phase of the disease, when an increase in the number of proliferating cells, both stem and OPC-NG2-positive cells, was found by us (24,31) and others (32,33). Also for DA rats, we confirmed the extensive presence of BrdUrduptaking cells Ͼ4 weeks after BrdUrd administration in the white matter of the spinal cord of EAE rats (Fig.…”

“…When administered during the acute phase of the disease, T4 favors lineage toward oligodendrocytes, as indicated by increased expression of the OPC marker PDGF␣R, increases expression of MBP, and favors myelin sheath reorganization, which returns to a thickness comparable to that in control rats. This result occurs only if T4 is administered in a time window, e.g., acute EAE, in which a large number of stem cells and OPCs are mobilized and extensive proliferative activity takes place (24,(31)(32)(33). We also found that axonal diameter of fibers in ventral funiculus of the spinal cord is increased in T4-treated compared with untreated EAE rats, suggesting a neuroprotective effect of T4.…”

Cognitive deficit associated with cholinergic and nerve growth factor down-regulation in experimental allergic encephalomyelitis in rats

“…1A reports the schedule of the experiment and clinical neurological score of experimental animals. As previously described (17,19,23,24), the severity of EAE, as evaluated by strength deficit, gradually increased, reaching its peak between 10 and 14 days postimmunization (dpi), and then partially recovered. In our experience (24), which was confirmed in this experiment, the disease relapses in the Lewis strain with lower severity in 60% of animals.…”

p75 Neurotrophin Receptor Expression Defines a Population of BDNF-Responsive Neurogenic Precursor Cells

“…It is highly expressed during development of the nervous system but is downregulated postnatally in most brain areas. However, some cells in the SVZ, which appear to be immature and mitotically active (Giuliani et al, 2004), continue to express significant levels of p75 NTR throughout adulthood (Yan and Johnson, 1989;Calza et al, 1998;Giuliani et al, 2004). Although p75…”

“…NTR -mediated signals have been shown to regulate proliferation and differentiation of neural and non-neural cells in vitro (Cattaneo and McKay, 1990;Seidl et al, 1998;Chittka and Chao, 1999), and p75 NTR expression in the SVZ can increase during periods of in vivo adult stem cell activity (Calza et al, 1998), the function of these SVZ cells and the role that p75 NTR plays in their regulation has not been reported.…”