Search

In vivo experiments with newborn rats show that neurotrophic factor derived from brain (BDNF) prevents the death of motor neurons that have been axotomized. BDNF appears to serve a mediating function in the regeneration of motor axons toward the periphery after neurons have been inflicted with lesions. They also promote the survival of motor neurons in vivo.

Neurotrophic factor derived from the brain or spinal cord can prevent the death of motor neurons which occurs after axotomy or the loss of targets, in addition to preventing natural motor neuron death. It also prevents the motor neuron death that normally follows the removal of descending afferent input. These results are from in vivo experiments performed on chick embryos, but they indicate the clinical potential of neurotrophins for treating motor neuron diseases.

Brain-derived neurotrophic factor (BDNF), when applied to transected sciatic nerve, prevents motor neurons from dying on a large scale as they usually do when axotomy is performed in the neonatal period. In experiments with rats, the BDNF is transported retrogradely by motor neurons. These results indicate that BDNF promotes the survival of motor neurons in vivo, and may regulate such survival during development. This may have clinical applications in the treatment of human disorders such as amyotrophic lateral sclerosis.

The first total synthesis of scabronine G in optically pure form is achieved in a high-yielding sequence from readily available materials. The sequence, which borrows primarily from the more classical canons of organic synthesis, lends itself to both multigram scale-up and to molecular modification.

Neurotrophins regulate neuronal cell survival and synaptic plasticity through activation of Trk receptor tyrosine kinases. Binding of neurotrophins to Trk receptors results in receptor autophosphorylation and downstream phosphorylation cascades. Here, we describe an approach to use small molecule agonists to transactivate Trk neurotrophin receptors. Activation of TrkA receptors in PC12 cells and TrkB in hippocampal neurons was observed after treatment with adenosine, a neuromodulator that acts through G protein-coupled receptors. These effects were reproduced by using the adenosine agonist CGS 21680 and were counteracted with the antagonist ZM 241385, indicating that this transactivation event by adenosine involves adenosine 2A receptors. The increase in Trk activity could be inhibited by the use of the Src family-specific inhibitor, PP1, or K252a, an inhibitor of Trk receptors. In contrast to other G protein-coupled receptor transactivation events, adenosine used Trk receptor signaling with a longer time course. Moreover, adenosine activated phosphatidylinositol 3-kinase/Akt through a Trk-dependent mechanism that resulted in increased cell survival after nerve growth factor or brain-derived neurotrophic factor withdrawal. Therefore, adenosine acting through the [A.sub.2A] receptors exerts atrophic effect through the engagement of Trk receptors. These results provide an explanation for neuroprotective actions of adenosine through a unique signaling mechanism and raise the possibility that small molecules may be used to elicit neurotrophic effects for the treatment of neurodegenerative diseases.

The neurotrophin hypothesis proposes that neurotrophins participate in activity-induced modification of synaptic transmission. Increasingly, evidence indicates that the synthesis, secretion and actions of neurotrophins on synaptic transmission are regulated by electrical activity and that neurotrophins themselves can acutely modify synaptic efficacy. Neurotrophins appear to exert either a permissive or instructive role on activity-dependent synaptic potentiation and depression, which depends on the particular synaptic connections and developmental stages. The characteristics of synaptic changes that are induced by neurotrophins suggest that this family of proteins is crucial for providing a molecular background in which activity-dependent plasticity can occur at selective synaptic sites within the neural network. Trends Neurosci. (2000) 23, 639-645

Increased expression of spinal cord Fos protein induced by bladder stimulation after spinal cord injury. Am J Physiol Regulatory Integrative Comp Physiol 279: R295-R305, 2000.--These studies examined Fos protein expression in spinal cord neurons synaptically activated by stimulation of bladder afferent pathways after spinal cord injury (SCI). In urethan-anesthetized Wistar rats after SCI for 6 wk, intravesical saline distension significantly (P [is less than or equal to] 0.005) increased the number of Fos-immunoreactive (IR) cells in the rostrolumbar (L1, 38 cells/section; L2, 29 cells/section) and caudal lumbosacral (L6, 140 cells/section; S1, 110 cells/section) spinal cord compared with control animals, but Fos expression in the L5 segment was not altered. The distribution of Fos-IR cells was also altered in the lumbosacral spinal cord. Significantly greater numbers of Fos-IR cells were distributed in the dorsal commissure and medial and lateral dorsal horn after intravesical distension in SCI animals. Large percentages of parasympathetic (75%) and sympathetic (85%) preganglionic neurons also expressed Fos-IR after intravesical distension in SCI animals. These results demonstrate that bladder distension produces increased numbers and an altered distribution pattern of Fos-IR cells after SCI. This pattern resembles that after noxious irritation of the bladder in control animals. Pretreatment with capsaicin significantly reduced the number of Fos-IR cells induced by bladder distension after SCI. These data suggest that SCI can reveal an altered Fos expression pattern in response to a nonnoxious bladder stimulus that is partially mediated by capsaicin-sensitive bladder afferents. lumbosacral spinal cord; neurotrophic factors; choline acetyltransferase; preganglionic neurons; urinary bladder dysfunction; capsaicin

The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron strongly depends on the instantaneous spatial pattern of ongoing population activity in a large cortical area. Very similar spatial patterns of population activity were observed both when the neuron fired spontaneously and when it was driven by its optimal stimulus. The evoked patterns could be used to reconstruct the spontaneous activity of single neurons., Conical neurons are spontaneously active in the absence of external input even in primary sensory areas (1). Analogously, dynamic patterns of ongoing population activity sweep across the cortex, as recently [...]

Many diseases off late are increasingly being caused due to neural damage and curing them has become a challenge. Researchers are developing medical implants, which can stimulate neurons to facilitate [...]

Molecular Cloning and Expression of Neuroleukin, a Neurotrophic Factor for Spinal and Sensory Neurons THE PRESENCE OF DENERVATED OR PARALYZED MUSCLE fibers within a muscle induces terminals of healthy motor [...]

The development and maintenance of function of the nervous system results from the concerted interaction of a great variety of genetic and epigenetic regulatory mechanisms. Transplantation and ablation experiments performed [...]

Neurotrophins are a family of homologous proteins, that include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), and they enable survival of the presynaptic neurons through retrograde signalling. The same neurotrophins can also operated by anterograde signalling, according to Altar and colleagues. A highly specific antiserum was used to identify BDNF protein and it was even found in regions of the brain that lack BDNF messenger RNA. BDNF immunoreactivity showed marked increases in the cortical neuron cell bodies, but decreases in the striatum.

The 75-kD neurotrophin receptor ([p75.sup.NTR]) has been an enigma for a decade. It was among the first growth factor receptors to be cloned (1), but until recently its function remained [...]

Dorsal root ganglion (DRG) neurons on attaining matured state showed no need for trophic support from nerve growth factor (NGF) and many other factors,indicating self-reliance capabilities development in the neurons. Neurons showed dependence on receiving signals for survival which were self-produced by the neurons in some cases. Development from target-derived survival signals to an autocrine supply of survival signals by neurons during growth is discussed.

The role of BDNF or brain-derived neurotrophic factor in pain signalling from the face is discussed. The discovery can prove useful in the treatment of facial pain.

Purification, Cloning, and Expression of Ciliary Neurotrophic Factor (CNTF) THE CHEMICAL AND NEUROTROPHIC PROPERTIES OF CNTF distinguish it from the only well-characterized neurotrophic factor, NGF, and suggest that it has [...]

Kafitz and colleagues have shown that neurotrophins may cause membrane depolarization within a few milliseconds, resulting in the firing of an action potential. This suggests that neurotrophins can both modulate and mediate chemical transmission. They studied the hippocampus, cortex and cerebellum of juvenile rats, and observed the rapid depolarization caused by brain-derived neurotrophic factor (BDNF).