Neural stem cells and cholinergic neurons: Regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factor

Abstract

Degenerative diseases represent a severe problem because of the very limited repair capability of the nervous system. To test the potential of using stem cells in the adult central nervous system as ''brain-marrow'' for repair purposes, several issues need to be clarified. We are exploring the possibility of influencing, in vivo, proliferation, migration, and phenotype lineage of stem cells in the brain of adult animals with selective neural lesions by exogenous administration (alone or in combination) of hormones, cytokines, and neurotrophins. Lesion of the cholinergic system in the basal forebrain was induced in rats by the immunotoxin 192 IgG-saporin. Alzet osmotic minipumps for chronic release (over a period of 14 days) of mitogens [epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF)] were implanted in animals with behavioral and biochemical cholinergic defect and connected to an intracerebroventricular catheter. After 14 days of delivery, these pumps were replaced by others delivering nerve growth factor (NGF) for an additional 14 days. At the same time, retinoic acid was added to the rats' food pellets for one month. Whereas the lesion decreased proliferative activity, EGF and bFGF both increased the number of proliferating cells in the subventricular zone in lesioned and nonlesioned animals. These results are indicated by the widespread distribution of BrdUrd-positive nuclei in the forebrain, including in the cholinergic area. Performance in the water maze test was improved in these animals and choline acetyltransferase activity in the hippocampus was increased. These results suggest that pharmacological control of endogenous neural stem cells can provide an additional opportunity for brain repair. These studies also offer useful information for improving integration of transplanted cells into the mature brain.

Neuroregulatory Events Follow Adaptive Immune-Mediated Elimination of HIV-1-Infected Macrophages: Studies in a Murine Model of Viral Encephalitis

“…We found an up-regulation of neurotrophic factors, including the nonneuronal growth factors, bFGF-2 and EGF. These two factors are involved in in vivo proliferation and migration of neuronal progenitor cells and can provide additional pathways for brain repair (52). Overexpression of IL-10 served in part to affect microglia inflammatory responses.…”

Molecular mechanisms of reversing neural degeneration by retinoic acid, a major derivative of vitamin A

“…Neural degeneration by a disease can have drastic effects on other body tissues as neurons have a paltrier ability to regenerate or to repair (Calza et al, 2003). This has been one of the major short comings of producing drugs to reverse the effects neuro degeneration.…”

“…Nevertheless the degenerated tissue is not replaced as immature nerve cells die before maturation (Arvidsson et al, 2002). Main governing factors for this inability for regeneration can be the hostile microenvironment, stem cell molecular mechanisms and inactive survival mechanisms or the type of lesion (Calza et al, 2003). Novel studies have shown that Neuron Growth Factor (NFG) and RA collectively aid the regulation of neural cell differentiation and juvenescence in the early growth stages of the human body (Bai et al, 2007;Zhang et al, 2010;Holst et al, 1997).…”

“…In order to survive in the hostile environments in neural blastema, the cells must arrest apoptosis. Except for the programmed cell death inducing signals produced by pathological conditions, growing stem cells produce apoptotic signals due to harsh environmental conditions (Calza et al, 2003). Retinoic acid is a key player activating antiapoptotic signals by accumulating pro survival molecules in to the cell (Blum and Begemann, 2012).…”

Role of Nerve Growth Factor in Assessing the Severity of Clinical Manifestations and Outcomes of Perinatal CNS Lesions in Infants

“…[13][14][15][16] The mechanisms underlying this neuroprotective role of NGF are not fully characterized, but several studies have shown its positive influence on cerebral blood flow, cellular Ca2+ homeostasis, and antioxidant activity. [13,14,[17][18][19] The purpose of our research was to analyze the association between the serum beta-NGF level and the severity of ND in children in the first year of life.…”