Biomedical subjects

G Kuchel

Publications and source records attributed to G Kuchel.

3 recordsLinked to original sources

PubMed1999

Nature of the retrograde signal from injured nerves that induces interleukin-6 mRNA in neurons.

In previous studies, interleukin-6 was shown to be synthesized in approximately one-third of lumbar dorsal root ganglion neurons during the first week after nerve transection. In present studies, interleukin-6 mRNA was found to be induced also in axotomized facial motor neurons and sympathetic neurons. The nature of the signal that induces interleukin-6 mRNA in neurons after nerve injury was analyzed. Blocking of retrograde axonal transport by injection of colchicine into an otherwise normal nerve did not induce interleukin-6 mRNA in primary sensory neurons, but injection of colchicine into the nerve stump prevented induction of interleukin-6 mRNA by nerve transection. Therefore, it was concluded that interleukin-6 is induced by an injury factor arising from the nerve stump rather than by interruption of normal retrograde trophic support from target tissues or distal nerve segments. Next, injection into the nerve of a mast cell degranulating agent was shown to stimulate interleukin-6 mRNA in sensory neurons and systemic administration of mast cell stabilizing agents to mitigate the induction of interleukin-6 mRNA in sensory neurons after nerve injury. These data implicate mast cells as one possible source of the factors that lead to induction of interleukin-6 mRNA after nerve injury. In search of a possible function of inducible interelukin-6, neuronal death after nerve transection was assessed in mice with null deletion of the interleukin-6 gene. Retrograde death of neurons in the fifth lumbar dorsal root ganglion was 45% greater in knockout than in wild-type mice. Thus, endogenous interleukin-6 contributes to the survival of axotomized neurons.

Animals↗

PubMed1997

Synaptic innervation density is regulated by neuron-derived BDNF.

In this report, we have examined the role of neuron-derived BDNF at an accessible synapse, that of preganglionic neurons onto their sympathetic neuron targets. Developing and mature sympathetic neurons synthesize BDNF, and preganglionic neurons express the full-length BDNF/TrkB receptor. When sympathetic neuron-derived BDNF is increased 2- to 4-fold in transgenic mice, preganglionic cell bodies and axons hypertrophy, and the synaptic innervation to sympathetic neurons is increased. Conversely, when BDNF synthesis is eliminated in BDNF -/- mice, preganglionic synaptic innervation to sympathetic neurons is decreased. Together these results indicate that variations in neuronal neurotrophin synthesis directly regulate neuronal circuitry by selectively modulating synaptic innervation density.

Animals↗

PubMedDate not supplied

Mutations of the notch3 gene in non-caucasian patients with suspected CADASIL syndrome.

The Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). To investigate the genetic contribution of Notch mutations in familial cases with vascular leukoencephalopathy, we screened 13 patients from 11 unrelated families, which were selected on the basis of magnetic resonance imaging findings and positive family history. We identified three different missense mutations in 5 patients from 4 families. Two (Arg90Cys and Arg133Cys) are the same as previously reported in Caucasian patients, the other (Cys174Phe) is a novel mutation causing a loss of a cysteine in epidermal-growth-factor-like repeats of Notch3. These data indicate that the CADASIL Notch3 mutations were found in approximately 35% of familial cases with leukoencephalopathy, suggesting genetic heterogeneity of the disease.

Adult↗