The Role of Neurotrophins During Early Development

Abstract

The effects of neurotrophins during the middle and late stages of development are well known. It was previously thought that neurotrophins had no role during early development, but this is not the case and is the subject of this review article. The earliest neurotrophin receptor expressed is that for neurotrophin-3 (NT-3). TrkC is detected in the neural plate and is present in the neural tube. Initially, the distribution of TrkC is homogenous, but it becomes localized to specific regions of the neural tube as the neural tube differentiates. The receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT-4/5), TrkB, is detected somewhat later than TrkC in the neural tube where it is also differentially localized. In contrast, the NGF receptor, TrkA, was not detected during early development. Both NT-3 and BDNF have been shown to have effects in vitro during early development. NT-3 caused an increase in neurite outgrowth and apoptosis in neural plate explants, and promoted differentiation of progenitors into motoneurons. BDNF increased the number of motoneurons in neural tube explants. These data suggest that NT-3 and BDNF may play a role during early development in vivo.

Brain Stem and Inner Ear Abnormalities in Children with Auditory Neuropathy Spectrum Disorder and Cochlear Nerve Deficiency

“…21 Expression of certain neurotrophic factors by the otocyst-chief among these being brain-derived neurotrophic factor and neurotrophin-3-is required for early cell migration, neurite outgrowth, and overall survival of vestibular and cochlear ganglion cells; absence of these factors has been shown to result in loss of ganglion cells. [28][29][30][31] The hindbrain also appears to play a role in CNVIII development, though to a lesser extent, and the exact signaling mechanisms underlying the trophic effects of the brain stem on cochlear ganglion cells and their axons are not understood. 32 Centrally directed processes of cochlear ganglion cells arrive and contact the brain stem by the fifth-to-sixth gestational week, 27 and cochlear nerve fibers begin to invade the cochlear nucleus by 16 weeks' gestation, subsequently forming synaptic connections.…”

Human Umbilical Cord-Derived Schwann-Like Cell Transplantation Combined with Neurotrophin-3 Administration in Dyskinesia of Rats with Spinal Cord Injury

“…As a neurotrophic factor found widely in mature and developing neural tissues, NT3 plays important roles in the neurogenesis and neural cell survival and repair [24]. Our results demonstrate that Schwann-like cell grafting combined with NT3 administration significantly promoted the survival and migration of HUMSC-derived Schwann-like cells grafted into the site of the SCI rats, also resulting in increased density of the grafted cells at the cell transplantation site as compared with Schwann-like cell grafting alone.…”

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

“…Many of the growth factor family proteins, including neurotrophins, mediate brain plasticity through multiple effects in the CNS that include neurite outgrowth, synaptogenesis, and neuronal differentiation and survival [96][97][98]. Brain injury elicits an increase in expression of multiple growth factors including neurotrophins, which is often transient and limited to traumatic penumbra [99][100][101].…”