Effects of Neurotrophic Factors in Glial Cells in the Central Nervous System: Expression and Properties in Neurodegeneration and Injury

Abstract

Astrocytes, oligodendrocytes, and microglia are abundant cell types found in the central nervous system and have been shown to play crucial roles in regulating both normal and disease states. An increasing amount of evidence points to the critical importance of glia in mediating neurodegeneration in Alzheimer’s and Parkinson’s diseases (AD, PD), and in ischemic stroke, where microglia are involved in initial tissue clearance, and astrocytes in the subsequent formation of a glial scar. The importance of these cells for neuronal survival has previously been studied in co-culture experiments and the search for neurotrophic factors (NTFs) initiated after finding that the addition of conditioned media from astrocyte cultures could support the survival of primary neurons in vitro . This led to the discovery of the potent dopamine neurotrophic factor, glial cell line-derived neurotrophic factor (GDNF). In this review, we focus on the relationship between glia and NTFs including neurotrophins, GDNF-family ligands, CNTF family, and CDNF/MANF-family proteins. We describe their expression in astrocytes, oligodendrocytes and their precursors (NG2-positive cells, OPCs), and microglia during development and in the adult brain. Furthermore, we review existing data on the glial phenotypes of NTF knockout mice and follow NTF expression patterns and their effects on glia in disease models such as AD, PD, stroke, and retinal degeneration.

PLG Bridge Implantation in Chronic SCI Promotes Axonal Elongation and Myelination

“…This mechanism has been suggested in other work combining IL-10 and NT-3 delivery for treatment of multiple sclerosis 61 . We did not observe an increase in oligodendrocyte myelination for NT-3 delivery alone, possibly due to lack of surviving oligodendrocytes and weak effects of NT-3 on their proliferation and differentiation 56 .…”

“…Oligodendrocyte proliferation is not altered by NT-3, NT-3 exposure in vitro lead to significantly more MBP production by oligodendrocytes through an unknown posttranscriptional mechanism 54,55 . Some evidence suggests that NT-3 weakly induces the maturation of neural precursor cells into myelinating oligodendrocytes 56 , yet other reports have shown NT-3 promotes quiescence or even Schwann cell differentiation of neural precursor cells 20,[57][58][59] . These differences could indicate concentration dependent effects or vary with surrounding interactions with other factors.…”

Microglia induce neurogenesis by stimulating PI3K/AKT intracellular signaling in vitro

“…Microglia can also secrete growth factors and neurotrophins [39]. Neurotrophin release may be enhanced when microglia respond to cortical injury [82,83]. Additional ELISA and RT-PCR analyses are required to determine whether neurotrophins or other soluble signals, such as prokineticins, contribute to the microglial-enhanced neurogenesis presented in this in vitro system [64].…”

Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

“…Beyond the intrinsic pathway, other limitations of CNS repair appear to be the existence of inhibitory molecules, including semaphorin 3a, semaphorin 3f and netrin receptor Unc5b, that block the axon growth [133]. Those inhibitory molecules diminish the regenerative effects of neurotrophic factors secreted from glial cells, such as astrocytes, oligodendrocytes and microglia, on axon regeneration [134]. If the CO/HO-1 circuit affects various neurotrophic factors and suppresses inhibitory molecules concomitantly, it may boost neurovascular regeneration.…”

“…GDNF mRNA levels can be detected in the developing brain and persist from the first postnatal day into adulthood [134,147]. The molecular complex GDNF and GDNF receptor family alpha 1 is critical for the morphological maturation of dendritic growth and synapse formation of postnatal and adult hippocampal neurons and is required for correct spatial pattern separation memory [147,148].…”