Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons from axotomy-induced death

Daniel A. Peterson, Carrie Phillipi, Douglas P. Murphy, Jasodhara Ray, Fred H. Gage

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The entorhinal cortex is a major relay between the hippocampus and other cortical and subcortical regions. Glutamatergic axons from layer II neurons form the entorhinal cortical projection to the hippocampus via the perforant pathway. We have demonstrated previously that lesion of the perforant pathway causes the death of ~30% of entorhinal layer II (ECL2) neurons. To elucidate mechanisms contributing to neuronal death and to investigate strategies preventing it, we identified the phenotype of the vulnerable neuronal population. Sections were immunolabeled with antibodies to the neuronal markers NeuN, glutamate, and calbindin-D(28k), and to receptors for fibroblast growth factor-2 (FGFR1) and NMDA (NMDAR1) and were examined using confocal microscopy. Calbindin immunoreactivity was strikingly lamina- specific to ECL2, where one-third of all ECL2 neurons were calbindin- positive. Localization of glutamate revealed that half of the glutamatergic ECL2 neurons coexpressed calbindin. Quantification using unbiased stereology at 9 weeks after lesion of the perforant pathway revealed that the only ECL2 neuronal population that experienced a significant (70%) loss (20% of the total) was the population of glutamatergic ECL2 neurons that did not coexpress calbindin. All ECL2 neurons expressed FGFR1; therefore, we tested the role of FGF-2 in the survival of glutamatergic ECL2 neurons. We grafted fibroblasts genetically engineered to express nerve growth factor or FGF-2 and found that only FGF-2 grafts prevented loss of the vulnerable glutamatergic/calbindin-negative neurons. We present a hypothesis for the selective vulnerability of these glutamatergic/calbindin-negative ECL2 neurons and address the role of FGF-2 in neuronal rescue.

Original languageEnglish (US)
Pages (from-to)886-898
Number of pages13
JournalJournal of Neuroscience
Volume16
Issue number3
StatePublished - Feb 1 1996
Externally publishedYes

Fingerprint

Axotomy
Fibroblast Growth Factor 2
Calbindins
Neurons
Perforant Pathway
Glutamic Acid
Hippocampus
Receptor, Fibroblast Growth Factor, Type 2
Entorhinal Cortex
Nerve Growth Factor
Vulnerable Populations
N-Methylaspartate
Confocal Microscopy
Population
Axons
Cause of Death
Fibroblasts
Transplants
Phenotype
Survival

Keywords

  • Alzheimer's disease
  • calbindin
  • calcium
  • excitotoxicity
  • fibroblast growth factor
  • glutamate
  • ischemia
  • neuronal death
  • neuroprotection
  • oxidative stress
  • stereology
  • trophic factors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons from axotomy-induced death. / Peterson, Daniel A.; Phillipi, Carrie; Murphy, Douglas P.; Ray, Jasodhara; Gage, Fred H.

In: Journal of Neuroscience, Vol. 16, No. 3, 01.02.1996, p. 886-898.

Research output: Contribution to journalArticle

Peterson, Daniel A. ; Phillipi, Carrie ; Murphy, Douglas P. ; Ray, Jasodhara ; Gage, Fred H. / Fibroblast growth factor-2 protects entorhinal layer II glutamatergic neurons from axotomy-induced death. In: Journal of Neuroscience. 1996 ; Vol. 16, No. 3. pp. 886-898.
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