TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous.

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.

Hippocampal tyrosine kinase A receptors are restricted primarily to presynaptic vesicle clusters.

Adult septohippocampal cholinergic neurons are dependent on trophic support for normal functioning and survival; these effects are largely mediated by the tyrosine kinase A receptor (TrkA), which binds its ligand, nerve growth factor (NGF), with high affinity. To determine the subcellular localization of TrkA within septohippocampal terminal fields, two rabbit polyclonal antisera to the extracellular domain of TrkA were localized immunocytochemically in rat dentate gyrus by light and electron microscopy. By light microscopy, TrkA immunoreactivity was found mostly in fine, varicose fibers primarily in the hilus and, to a lesser extent, in the granule cell and molecular layers. By electron microscopy, the central and infragranular regions of the hilus contained the highest densities of TrkA-immunoreactive profiles. Most TrkA-labeled profiles were axons (31% of 3,473), axon terminals (20%), and glia (38%); fewer were dendrites (6%), dendritic spines (5%), and granule cell and interneuron somata (<1%). TrkA immunolabeling in axons and axon terminals was discrete, often concentrated in patches of small synaptic vesicles that were adjacent to somatic and dendritic profiles. TrkA-labeled terminals formed both asymmetric and symmetric synapses, primarily with dendritic shafts and spines. TrkA-immunoreactive glial profiles frequently apposed terminals contacting dendritic spines. The findings that presynaptic profiles contain TrkA immunolabeling in sites of vesicle accumulation suggest that NGF binding to TrkA may influence transmitter release. The presence of TrkA immunoreactivity in somata, dendrites, and glia further suggests that cells within the dentate gyrus may take up NGF.