Maintaining the neuronal phenotype after injury in the adult CNS

Abstract

Multiple genetic and epigenetic events determine neuronal phenotype during nervous system development. After the mature mammalian neuronal phenotype has been determined it is usually static for the remainder of life, unless an injury or degenerative event occurs. Injured neurons may suffer one of three potential fates: death, persistent atrophy, or recovery. The ability of an injured adult neuron to recover from injury in adulthood may be determined by events that also influence neuronal phenotype during development, including expression of growth-related genes and responsiveness to survival and growth signals in the environment. The latter signals include neurotrophic factors and substrate molecules that promote neurite growth. Several adult CNS regions exhibit neurotrophic-factor responsiveness, including the basal forebrain, entorhinal cortex, hippocampus, thalamus, brainstem, and spinal cord. The specificity of neurotrophic-factor responsiveness in these regions parallels patterns observed during development. In addition, neurons of several CNS regions extend neurites after injury when presented with growth-promoting substrates. When both neurotrophic factors and growth-promoting substrates are provided to adult rats that have undergone bilateral fimbria-fornix lesions, then partial morphological and behavioral recovery can be induced. Gene therapy is one useful tool for providing these substances. Thus, the mature CNS remains robustly responsive to signals that shape nervous system development, and is highly plastic when stimulated by appropriate cues.

Pseudorabies Virus-Based Gene Delivery to Rat Embryonic Spinal Cord Grafts

“…As concerns grafted embryonic neurons, it would be optimum to induce the expression of neuroprotective molecules only for the period during which the grafted neurons settle and integrate in the host cord, differentiate to a limited extent, establish interaction with the host cord, and extend their axons to the target (Tuszynski and Gage, 1995;Nakahara et al, 1996). This period is estimated as about 8-10 weeks for spinal cord grafts.…”

“…N EURONS THAT ARE SEVERELY DAMAGED during development or adult life can be rescued by various methods, including the delivery of neuroprotective substances (Tuszynski and Gage, 1995;Fawcett, 1998). The various virus-based systems have been found to be superior over other approaches as their use produces the required effects only in the targeted cells, without systemic effects.…”

Amino-Nogo Inhibits Optic Nerve Regeneration and Functional Recovery via the Integrin αv Signaling Pathway in Rats

“…The optic nerve as a part of CNS, damage to which is difficult to regenerate [20,21,22,23]. RGCs axons form the optic nerve, injury of which is one of the causes of visual loss.…”

Neural stem cell therapy for neurodegenerative disorders: The role of neurotrophic support

“…Among the most prominently studied neurotrophic factors in the CNS are NGF, brain-derived neurotrophic factor (BDNF), glial cell line derived neurotrophic factor (GDNF), and insulin-like growth factor 1 (IGF-1). These neurotrophins and their receptors are highly expressed in both the human and rodent CNS (Adem et al, 1989, Kawamoto et al, 2000, Lu et al, 1989, Tang et al, 2010) and research has demonstrated critical roles for these factors in the growth and stabilization of dendritic spines, synaptic plasticity, long-term potentiation, survival of neurons and glia, and therefore unsurprisingly learning and memory (for review see (Vicario-Abejón et al, 2002, Arancio and Chao, 2007, Park and Poo, 2013, Russo et al, 2005, Tuszynski and Gage, 1995). …”