STEROID HORMONES AND NEURONAL REGENERATION

Project: Research project

Description

From studies of gonadal steroid hormone action on the brain, it is
generally established that these agents exert neurotrophic effects on many
aspects of neuronal viability and functioning. Recent clinical and
experimental evidence suggests that gonadal may have a therapeutic role in
promoting neuronal regeneration. We have recently demonstrated that
systematic administration of the androgen, testosterone propionate(TP), to
adult male hamsters accelerates functional recovery from facial paralysis
induced by facial nerve crush. Importantly, facial motoneurons contain
androgen receptors. How TP accomplishes this therapeutic effect is not
known. The long term objective of our research is to determine the
mechanism underlying the TP-acceleration of recovery from facial nerve
damage. Toward that objective, the specific aims of this proposal will be
to test the following 4 hypotheses. The first hypothesis to be tested is
that TP accelerates recovery from facial paralysis following facial nerve
crush by increasing the growth rate of regenerating axons and/or
shortening the initial delay of sprout formation. Two series of
experiments, involving radioisotopic labeling of axonally transported
proteins, will be employed to assess the effects of TP on axonal
regenerative properties. The second hypothesis to be tested is that the
TP-induced acceleration of functional recovery following peripheral nerve
injury is androgen receptor-mediated. Two series of experiments will be
done to determine if the action of TP on injured neurons is androgen
receptor-mediated. In the first, androgen receptors will be blocked, the
facial nerve crush axotomized, and the effects of TP on functional
recovery determined. In the second, a population of motor neurons that do
not have androgen receptors (cranial nerve VI) will be subjected to crush
axotomy and the effects of TP on functional recovery determined. The
third hypothesis to be tested is that TP-accelerated recovery from facial
paralysis following facial nerve crush involves alterations in ribosomal
RNA gene expression in facial motoneurons. The effects of gonadal
steroids in the brain are thought to occur through alterations in neuronal
gene expression. Ribosomal RNA represents an abundant, readily
quantifiable RNA species that is known to be affected by axotomy and by
steroid hormone action on target neurons. In situ hybridization with a
genomic ribosomal DNA probe will be employed to determine if significant
alterations in the pattern of rRNA expression occur in injured facial
neurons following TP exposure. The fourth hypothesis to be tested is that
TP-accelerated recovery from facial paralysis following facial nerve crush
involves alterations in protein synthesis within faci: motoneurons.
Hormonal regulation of target tissue functioning is generally considered
to occur through selective changes in the expression of proteins. Axotomy
also has been demonstrated to selectively affect protein synthesis in
regenerating neurons. Radioactive labeling and two-dimensional gel
electrophoresis will be done to identify TP-induced changes in protein
synthesis in injured facial neurons.
StatusFinished
Effective start/end date1/1/907/31/06

Funding

  • National Institutes of Health: $135,482.00
  • National Institutes of Health
  • National Institutes of Health: $105,085.00
  • National Institutes of Health: $246,359.00
  • National Institutes of Health: $50,000.00
  • National Institutes of Health
  • National Institutes of Health: $192,067.00
  • National Institutes of Health
  • National Institutes of Health: $59,200.00
  • National Institutes of Health
  • National Institutes of Health: $231,680.00
  • National Institutes of Health: $105,313.00
  • National Institutes of Health: $312,886.00
  • National Institutes of Health

Fingerprint

Testosterone Propionate
Regeneration
Steroids
Hormones
Androgen Receptors
Facial Nerve
Nerve Regeneration
Motor Neurons
Facial Nerve Injuries
Cricetinae
Flavin Mononucleotide
Neurons
Nerve Crush
In Situ Hybridization
Androgens
Axotomy
Messenger RNA
Wounds and Injuries
Facial Paralysis
Ribosomal DNA

ASJC

  • Medicine(all)
  • Neuroscience(all)