Bovine basic fibroblast growth factor (bFGF) is a potent mitogen isolated from bovine pituitary glands and brain. The addition of homogeneous bFGF to primary cultures of rat cerebral cortical neurons markedly enhances cell survival and elaboration of neurites. These effects are dose-dependent, with optimal stimulation occurring at a concentration of 500 pg/ml. Maintenance of survival and neurite outgrowth require the continuous presence of bFGF. Other growth factors, such as thrombin, platelet-derived growth factor, beta nerve growth factor, and interleukin 2, have no effect on neuronal survival or process formation. Although the cellular site(s) of bFGF synthesis has not yet been established, these results suggest that bFGF may function as a neurotrophic agent in the central nervous system.

https://www.pnas.org/content/pnas/83/19/7537.full.pdf

Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture

Partial denervation or paralysis of adult skeletal muscle is followed by nerve sprouting, probably due to release of diffusible sprout-inducing activity by inactive muscle. Insulin-like growth factors (IGF1 and IFG2) are candidates for muscle-derived sprouting activity, because (a) they induce neurite growth from peripheral neurons in vitro; and (b) their mRNA levels in adult skeletal muscle increase severalfold after denervation or paralysis. We sought to determine whether the presence of elevated levels of IGFs in innervated adult skeletal muscle was sufficient to produce intramuscular nerve growth. Low concentrations of IGFs induced massive neurite growth from enriched embryonic chick motoneurons in vitro. Half-maximal responses required 0.2 nM IGF2 or IGF1, or 20 nM insulin. Similar hormone binding properties of motoneuron processes in vitro were observed. Exposure of adult rat or mouse gluteus muscle in vivo to low quantities of exogenous IGF2 or IGF1 led to intramuscular nerve sprouting. Numbers of sprouts in IGF-exposed muscles were 10-fold higher than in vehicle-exposed or untreated muscles, and 12.2% of the end plates in IGF-exposed muscle (control: 2.7%) had sprouts growing from them. The nerve growth reaction was accompanied by elevated levels of intramuscular nerve-specific growth-associated protein GAP43. Additional properties of IGF-exposed muscle included modest proliferation of interstitial cells and elevated interstitial J1 immunoreactivity. These results suggest that elevated levels of IGFs in denervated or paralyzed muscle might trigger coordinate regenerative reactions, including nerve sprouting and expression of nerve growth-supporting substrate molecules by activated interstitial cells.

/pdf/nerve-sprouting-in-innervated-adult-skeletal-muscle-induced-4awlrcl2c7.pdf

Nerve sprouting in innervated adult skeletal muscle induced by exposure to elevated levels of insulin-like growth factors.

The repetitive stochastic patterns of eye dominance and orientation preference found in the mammalian visual cortex have attracted much attention from theoretical neurobiologists during the last two decades. Reasons for this include the visually intriguing nature of the patterns and the fact that many aspects of their development seem likely to be dependent upon both spontaneous and visually driven patterns of neural activity. Understanding these processes holds out the promise that general theories of learning and memory may be derived from those found to be applicable to the visual cortex. It has turned out, in fact, that remarkably simple models, based on Hebbian synaptic plasticity, intracortical interactions and competitive interactions between cells and growing axons, have been able to explain much of the phenomenology. This article reviews the models of topographic organization in the visual cortex in a roughly historical sequence, beginning with von der Malsburg's paper 1973 paper in Kybernetik on self-organization of orientation selectivity. The principles on which each of the models is based are explained, and the plausibility of each model and the extent to which it is able to account for the relevant experimental data are evaluated. Attention is drawn to the underlying similarities and differences between the models and suggestions are made for future directions in research.

The development of topography in the visual cortex: a review of models.

We have used immunofluorescence and immunoblotting methods to study the amount and distribution of the neural cell adhesion molecule (N-CAM) in rat skeletal muscle; this molecule is thought to mediate adhesion of neurons to cultured myotubes. N-CAM is present on the surface of embryonic myotubes, but it is lost as development proceeds and is nearly absent from adult muscle. However, denervation of adult muscle results in the reappearance of N-CAM. In denervated muscle, N-CAM is associated both with muscle fibers and with cells in interstitial spaces between fibers. The N-CAM in interstitial spaces is concentrated near denervated endplates, which are known to be preferential sites for reinnervation. Paralysis of innervated muscle, known to mimic denervation in many respects, also induces the accumulation of N-CAM. Axons that regenerate to reinnervate muscle bear N-CAM on their terminals, and reinnervation results in the disappearance of N-CAM from muscle. Denervation induces accumulation of N-CAM in mouse and chicken, as well as in rat muscles. Thus, the expression of N-CAM in muscle is regulated by the muscle's state of innervation. In that N-CAM-rich muscles (embryonic, denervated, and paralyzed) are known to be competent to accept synapses, while N-CAM-poor muscles (normal adult and reinnervated) are refractory to hyperinnervation, N-CAM might, in turn, participate in regulating muscle's susceptibility to innervation.

https://www.pnas.org/content/pnas/82/13/4544.full.pdf

Neural cell adhesion molecule (N-CAM) accumulates in denervated and paralyzed skeletal muscles.

The complexity and remarkable specificity found in the nervous system chal­ lenge the investigator to identify molecular mechanisms guiding neuronal development. Cell-cell interactions mediated by diffusible substances have frequently been suggested to play an important role. Studies on naturally occurring cell death in the nervous system provided early evidence for such interactions by demonstrating that neuronal survival beyond a critical period in development requires interaction between the neurons and the postsynaptic target tissue (for a review see Oppenheim 1981). The discovery of Nerve Growth Factor (NGF) raised the possibility that neuronal development, includ­ ing target-dependent neuronal survival, might be mediated by diffusible mole­ cules. NGF can be isolated as a 140,000 dalton protein complex (7S NGF) of heterologous subunits or as a 26,500 dalton component (beta-NGF) containing two identical polypeptide chains. Experiments in vivo indicate that NGF can reverse naturally occurring as well as experimentally induced cell death in sympathetic and sensory neurons; moreover, anti-NGF antibodies in vivo can block the development of the sympathetic nervous system (for reviews see Thoenen & Barde 1980, Hamburger et al 1981, Levi-Monta1cini 1982). That NGF might also influence the choice of targets contacted by neurons is suggested by studies in cell culture showing that NGF can change the direction of neuritic growth (Gundersen & Barrett 1979) and can help shape the neuritic tree maintained by the neuron (Campenot 1982). Naturally occurring cell death has been documented for almost every popula­ tion of vertebrate neurons studied (Oppenheim 1981), and every neuron is faced with the problem of finding appropriate target cells. Only sensory and sympathetic neurons, however, have been convincingly shown to depend on

J.R. Slack

Papers

Terminal sprouting of motoneurones is a local response to a local stimulus.

Motor neurotrophic factor in denervated adult skeletal muscle.

Source of the stimulus for nerve terminal sprouting in partially denervated muscle

Neuromuscular transmission at terminals of sprouted mammalian motor neurones.

Interaction between foreign and regerating axons in axolotl muscle