Physiology of the Neurotrophins

Abstract

The neurotrophins are a small group of dimeric proteins that profoundly affect the development of the nervous system of vertebrates. Recent studies have established clear correlations between the survival requirements for different neurotrophins of functionally distinct subsets of sensory neurons. The biological role of the neurotrophins is not limited to the prevention of programmed cell death of specific groups of neurons during development. Neurotrophin-3 in particular seems to act on neurons well before the period of target innervation and of normally occurring cell death. In animals lacking functional neurotrophin or receptor genes, neuronal numbers do not seem to be massively reduced in the CNS, unlike in the PNS. Finally, rapid actions of neurotrophins on synaptic efficacy, as well as the regulation of their mRNAs by electrical activity, suggest that neurotrophins might play important roles in regulating neuronal connectivity in the developing and in the adult central nervous system.

Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival

“…Growth factors and neurotrophins participate to these events. 1 The Ras/Erk MAPK pathway and other pathways controlled by Cdc42 and Rac GTPases also modulate neurite growth. 36 However, how these signals work together in a given cell to determine when and where the neurite, or a ramification, has to grow, and then, when and where, it has to stop, is not yet well understood.…”

“…1 At the cellular level, BDNF induces neuronal differentiation and neurite outgrowth, 2 facilitates plasticity, 3 and favors neuronal survival. 4 BDNF binds to the tyrosine kinase receptor TrkB, which activates at least three signal transduction pathways: (i) the Ras/mitogen-activated protein (MAP) kinase (Ras/MAPK) pathway; (ii) the PI3-Kinase/Akt pathway; and (iii) the PLCg pathway.…”

Interaction between BDNF and Serotonin: Role in Mood Disorders

“…Initially isolated as a secretory protein capable of promoting the survival of peripheral neurons, BDNF is now recognized as a plethoric factor able to regulate a wide repertoire of functions, including neuronal survival, migration, phenotypic differentiation, axonal and dendritic growth, and synapse formation (Huang and Reichardt, 2001;Lewin and Barde, 1996). In addition to its prominent role in neuronal survival and differentiation during development, BDNF has emerged as a key regulator of synaptic plasticity and behavior (McAllister et al, 1999;Poo, 2001;Lu, 2003).…”

Regeneration of lesioned corticospinal tract fibers in the adult rat spinal cord under experimental conditions

“…Several of the recently discovered neurotrophic factors can rescue these lesioned neurons if applied into the CNS of experimental animals. 10,11 Lesioned adult axons grow sprouts in response to injury…”

“…10,49,50 Infusions of some of these factors or local implantation of ®broblasts producing these factors from a transgene have been analysed in spinal cord lesions. 51,52 Enhanced sprouting and growth of axons were found.…”