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Neurotrophic factors are important regulators of the development and maintenance of vertebrate nervous system. During the development of the nervous system, neuronal populations undergo a process of naturally occurring cell death at a time when their axons are innervating target areas. This mechanism ensures a balance between the size of an innervating population and the size of its target territory. Nerve growth factor (NGF) was the first neurotrophic factor to be discovered. More recent work has shown that other molecules are secreted by target organs that regulate neuronal survival and differentiation. This chapter focuses on neurotrophins with brief descriptions of the actions of these other molecules.

This chapter details early studies on the development of nerve cells. The nervous system arises from a single fertilized egg. Classical histologists visualized this process through the cells of the changing embryo. The first great synthesis was the idea of an organizer that directed the formation of the organs. The crux for the nervous system was how connections are established between cells, which implied the presence of intercellular signals. The clearest evidence for such a signal, called “nerve growth factor”, was reported in 1951. Subsequent experiments identified its molecular structure, which came to be known as NGF, the first of a growing number of neurotrophic and neurotrophic factors involved in neural development and in the plasticity of connections that underlie learning, memory, and response to injury.

Roger W. Sperry earned a reputation for his ability to design critical experiments that demanded looking at the growing and functioning nervous system in new ways. Sperry's most important discoveries fall into two distinct domains. The first group began in the 1940s and concerned how axons grow to their proper places. Early in the 1950s, having established a name in neurobiology, Sperry became interested in the role of the corpus callosum, the massive band of axons connecting the right and left cerebral hemispheres. Other mid-20th-century researchers were soon able to prove that chemical growth and guidance factors exist. The individual most responsible for this ground-breaking work was Rita Levi-Montalcini, who discovered the nerve growth factor. Levi-Montalcini is important for neuroscience because she was able to demonstrate that Sperry was headed in the right direction when he brought up the possibility of chemical guidance in the 1940s. This chapter looks at the work of Sperry and Levi-Montalcini on neural growth, split brains, chemoaffinity, visual system, and consciousness.

This chapter shows that various compounds (such as NO and various hormones, and cytokines) share three main functional features. They are released in response to neural activity; they are somnogenic; and they trigger a cascade of events involved in neural plasticity. After reviewing the somnogenic factors which are released in an activity-dependent manner, the chapter focuses on two examples, more closely related to neural plasticity: the expression of nerve growth factor (NGF), a neurotrophin involved in neural plasticity, which is modulated by sleep/sleep deprivation only in neurones with an elevated activity during previous waking periods; and metalloproteinase-9 which is involved in the interaction between neurones and extracellular matrix, a critical feature in neural plasticity. It is shown that sleep deprivation modifies the cerebral expression of the metalloproteinase-9 induced by spatial learning.

Abstract: This chapter informs the reader of the discovery of nerve growth factor, how it plays an important role in bioprinting by directing the growth of the axons of nerve cells along specific paths to repair peripheral nerve injuries, and of the nascent efforts in bioprinting spinal cord scaffolds that may aid in the repair of spinal cord injuries. The chapter apprises the reader of the glial family of cells that provide myelination (insulation) for nerves in the central nervous system. Glial cells are as numerous in the central nervous system (i.e., the brain and spinal cord) as neurons (nerve cells). The chapter also explains fluorescently tagged calcium ion flow within bioprinted nerve tissue. Intracellular calcium—calcium within cells—controls key cellular functions in all types of neurons. For example, nerve cells cause a release of calcium ions that initiate muscle contraction.

The notion that specialized nociceptors exist among the afferent fibre population is a relatively recent one. Although indirect evidence for the existence of these fibres had been available for many years, it was not until much later that definitive single-unit studies revealed the presence of neurones selectively activated by stimuli that are potentially damaging to the skin. These studies in the cat clarified that there are two major groups of nociceptive afferents, one of which conducts in the Αδ conduction velocity range and the other of which conducts in the C-fibre range. The former are innervate receptors that are high-threshold mechanoreceptors (HTMs), whereas the latter are more diverse in their properties with many being sensitive to multiple modalities of stimulation (mechanical, thermal, chemical) giving rise to the name polymodal nociceptor. More recently, these two groups of fibres have been identified in the rat. This chapter focuses on the development of nociceptors, and particularly on the role of nerve growth factor (NGF) in determining the development of these sensory receptors.

This chapter describes the connection between the nerve growth factor (NGF) and Alzheimer’s disease (AD). It reveals that NGF can be considered as an anti-amyloidogenic factor that normally keeps the amyloidogenic pathway under control. It states that the experimental study of AD11 neurodegeneration exhibited a novel causal connection between neurotrophic signaling deficits and Alzheimer’s neurodegeneration. This chapter shows the therapeutic potential of the painless NGF molecules, displaying full neurotrophic activity and reduced pain-related signaling capability.

The developing nervous system produces about twice as many neurons as will survive into adulthood, and then at the end of development, around the time of birth in mammals, there is a short period termed the ‘period of ontogenetic cell death’ during which about half the neurones die. Trophic factors have a well-characterised role in the control of this process. The first trophic factor to be characterised was nerve growth factor (NGF): Rita Levi-Montalcini and Stanley Cohen received a Nobel prize for their pioneering work in the identification of this molecule. Subsequently, many other neuronal trophic factors have been discovered, many of them mentioned later in this chapter, but NGF has provided the prototype for all that followed.

This chapter describes neurotrophins as regulators of visual cortical plasticity. It illustrates that brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are popular candidate molecules for synaptic plasticity. It supports the hypothesis that antidepressant drugs might increase neuronal plasticity in the cortex at least partially by activating BDNF signaling in brain. This chapter also shows the role of antidepressants as enhancers of plasticity, which is consistent with the fact that these drugs are successfully employed for the treatment of many neuropsychiatric disorders in addition to depression, including anxiety, obsessive-compulsive disorder, chronic pain, and eating disorders.