by Steven W. Barger, Ph.D., posting from the account of
mpm at seqanal.mi.uky.edu (Mark Mattson):
>RSTETTA at DELPHI.COM (rstetta at news.delphi.com) wrote:
> : Looking for info on what Nuerotrophic Factors consist of,
> : and what effects them.
> : There is a form of muscular dystrophy, spinal muscle atrophy,
> : in which the motor nuerons are affected, weaken over time.
> : It is similiar to ALS (amyotrophic lateral sclerosis) but
> : progresses at a much slower rate.
> : The info I have comes second hand from my sister in Tucson
> : who attended a conference where a researcher from Canada
> : mentioned these neurotrophic factors.
> The prototype is nerve growth factor (NGF), now recognized as a member of
> a family of related peptides termed "neurotrophins" which all support the
> health and/or growth of neurons. Different family members seem to be
> important for different types of neurons, but (as far as I know) none of
> these has been shown to be trophic for the motor neurons which are lost
> in ALS. These cells may be more dependent on other factors produced by the
> muscles they innervate.
In fact, there is a young but rich literature indicating that at least one
of the neurotrophins (brain-derived neurotrophic factor, or BDNF) has a
profound trophic influence on exactly the motor neurons in question.
I think the earliest indications of an effect of neurotrophins on spinal
motor neurons came from observations that spinal MNs expressed the p75
neurotrophin receptor (also known as the low-affinity NGF receptor). More
direct evidence for a survival effect of neurotrophins came from a series
of 3 reports published in the 24/31 Dec. 1992 issue of Nature, all
demonstrating that BDNF could rescue spinal motor neurons from death,
both the naturally-occurring cell death that occurs in chick embryonic
development and the axotomy-induced cell death that occurs after nerve
section in newborn rats. The strongest evidence was published in the
20 May 1993 issue of Nature in a study combining analysis of neuron
survival in cell culture with analyses of the expression of genes
encoding neurotrophins and their specific receptors. Here is an
excerpt from the abstract: "...picomolar concentrations of ...
brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-5,
can prevent the death of cultured embryonic rat spinal motor neurons.
Furthermore, messenger RNA coding for neurotrophins is present at
appropriate stages in spinal cord and limb bud, and mRNA for their
receptors is found in motor neurons. These neurotrophins may
therefore be physiological motor neuron growth factors."
The significance of these studies in terms of treatment of ALS
and/or other degenerative disorders of motor neurons is mentioned
in every article.
Sendtner et al. (1992) Brain-derived neurotrophic factor
prevents the death of motoneurons in newborn rats
after nerve section. Nature 360:757-9.
Yan et al. (1992) Brain derived neurotrophic factor rescues
spinal motor neurons from axotomy-induced cell death.
Oppenheim et al. (1992) Brain-derived neurotrophic factor
rescues developing avian motoneurons from cell death.
Henderson et al. (1993) Neurotrophins promote motor neuron
survival and are present in embryonic limb bud.
For a nice, quick review see the News & Views accompanying the
Henderson et al. paper on p. 213 of the 20 May 1993 Nature.
Steve Matheson Program in Neuroscience University of Arizona
sfm at neurobio.arizona.edu