Neurotrophin Actions in the Injured Brain

Project Details

Description

DESCRIPTION (provided by the applicant): Neurotrophins have long been known to
support the survival and differentiation of many neuronal populations through
interactions with the trk tyrosine kinase receptors. Recent studies from our
laboratory and others have demonstrated that neurotrophins can also elicit cell
death via the p75 receptor. Thus, whether a neuron survives or dies in response
to neurotrophins may depend on a balance of signaling pathways activated by
these different receptors. Although p75 is transiently expressed in many CNS
neuronal populations during development, this receptor is not widely expressed
in the normal adult brain. However, after damage in the brain expression of p75
can be detected in numerous neurons, suggesting that upregulation of this
receptor may be part of an injury or stress response. Since production of NGF
is also induced in the brain by many types of damage, we hypothesize that NGF
interacts with p75 to eliminate neurons that are compromised by damage.
In this grant application we propose to investigate whether the p75 receptor is
expressed on dying neurons in vivo as a consequence of pilocarpine-induced
seizures. We will compare the number of dying neurons after seizure in normal
mice with p75-/- mice to assess the role of this receptor in mediating neuronal
loss. These in vivo studies will be accompanied by studies on hippocampal
neurons in vitro to investigate the mechanisms of p75-mediated neuronal death.
Thus, the goal of these studies is to define the role of the p75 neurotrophin
receptor in mediating cell death in hippocampal neurons, particularly under
conditions of brain injury.
StatusFinished
Effective start/end date7/15/0211/30/14

Funding

  • National Institutes of Health: $221,588.00
  • National Institutes of Health: $331,209.00
  • National Institutes of Health: $331,209.00
  • National Institutes of Health: $221,588.00
  • National Institutes of Health: $248,529.00
  • National Institutes of Health: $334,590.00
  • National Institutes of Health: $319,617.00
  • National Institutes of Health: $216,380.00
  • National Institutes of Health: $337,969.00
  • National Institutes of Health: $221,588.00

ASJC

  • Medicine(all)
  • Neuroscience(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.