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Keywords:

  • nerve growth factor;
  • electron microscopy;
  • growth factors;
  • estrogen

Abstract

Neurotrophins are important modulators of structural synaptic plasticity. (Through trophic action (Jordan. J Neurobiol 40:434–445, 1999), astrocytes serve as permissive substrates to support axonal regrowth (Ridet et al. Trends Neurosci 20:570–571, 1997), and are involved in estrogen-induced synaptic structural plasticity (Garcia-Segura et al. Cell Mol Neurobiol 16:225–237, 1996). Previously, we reported that tyrosine kinase A receptor (TrkA) immunoreactivity was present both in presynaptic neuronal processes (axons and terminals) and in select astrocytes of the male rat hippocampal formation (Barker-Gibb et al. J Comp Neurol 430:182–199, 2001). We show that the number of TrkA-immunoreactive astrocytes in female rats fluctuates 16-fold across the estrous cycle in dendritic fields of the hippocampal formation, with the greatest number at estrus after the peak plasma estradiol concentration of proestrus. Few TrkA-labeled astrocytes were found in ovariectomized animals; after estrogen replacement, this number increased by 12-fold in the hippocampal formation, indicating estrogen-mediated induction. Dual-labeling studies showed that TrkA-labeled astrocytes were also immunoreactive for vimentin, a protein expressed by reactive astrocytes. Ultrastructural analysis of the dentate gyrus molecular layer demonstrated that TrkA immunoreactive astrocytes are positioned primarily next to dendrites and unmyelinated axons. Because nerve growth factor (NGF) has been reported to stimulate astrocytes to function as substrates for axon growth (Kawaja and Gage. Neuron 7:1019–1030, 1991), these findings are consistent with the theory that TrkA immunoreactive astrocytes serve a role in structural plasticity, axon guidance, and synaptic regeneration across the estrous cycle in the hippocampal formation. GLIA 38:36–44, 2002. © 2002 Wiley-Liss, Inc.