p75NTR immunoreactivity in the rat dentate gyrus is mostly within presynaptic profiles but is also found in some astrocytic and postsynaptic profiles

Abstract

To localize neurotrophin binding sites within the rat dentate gyrus, the distribution of low‐affinity p75 neurotrophin receptor (p75NTR) immunoreactivity (IR) was examined by using antiserum raised against the cytoplasmic domain of the receptor. Semiquantitative electron microscopic examination of p75NTR‐labeled sections showed that most p75NTR‐labeled profiles were axons and axon terminals (72% from a total of 3,975); p75NTR‐IR was observed throughout the extent of these structures and was not limited to the plasmalemmal surface. Axons and axon terminals containing p75NTR‐IR were distributed in approximately equal proportions across the hilus, infragranular zone, and the inner, middle, and outer molecular layers; significantly fewer p75NTR‐labeled profiles were observed in the granule cell layer. Axon terminals containing p75NTR‐IR, which made synapses (296 of 552), formed equal proportions of symmetric and asymmetric synapses, primarily with the shafts and spines of dendrites. The remainder of the p75NTR‐labeled terminals apposed unlabeled somata and dendrites without forming synapses in the single sections analyzed. In addition, p75NTR‐IR was contained within some astrocytes (17.5% of 3,975) and dendritic shafts (3%) and spines (5%). Within dendritic spines, p75NTR‐IR was most often associated with the plasmalemmal surface near postsynaptic densities; in dendritic shafts, p75NTR labeling was associated with microfilaments distant from the plasmalemma. Most p75NTR‐labeled dendritic profiles were located in the molecular layer, and some originated from granule cells. Moreover, in some granule cell somata (<1% of 3,975), p75NTR‐IR was associated with endosomes. The primary localization of p75NTR‐IR to presynaptic structures in the dentate gyrus, presumably arising from medial septal/diagonal band neurons, agrees with previous reports. However, p75NTR‐IR within some astrocytes, somata, and dendritic structures suggests that this receptor may also be involved in controlling local neurotrophin levels and possibly modulating the viability of local hippocampal cell populations. J. Comp. Neurol. 407:77–91, 1999. © 1999 Wiley‐Liss, Inc.

Neurotrophin receptor p75NTR mediates Huntington’s disease–associated synaptic and memory dysfunction

“…However, recent evidence in vivo and in vitro also demonstrates dendritic spine localization of p75 NTR in CA1 and dentate gyrus of hippocampal neurons (19,23,85,86). In accordance with these studies, we found colocalization of p75 NTR with MAP2 and PSD95 in hippocampal pyramidal neurons of CA1, revealing a postsynaptic localization of p75 NTR .…”

“…Besides p75 NTR expression in neurons, it has been reported that astrocytes induce p75 NTR expression after different types of injury (36,86,87). Increased levels of p75 NTR have been detected in both neurons and astrocytes in the hippocampal CA3 region after seizures (37).…”

Adeno-Associated Virus Vector Expressing Nerve Growth Factor Enhances Cholinergic Axonal Sprouting after Cortical Injury in Rats

“…The p75 receptor is distributed throughout the dentate in a pattern resembling the AChE-containing septodentate input (Peterson et al, 1994). In addition, the p75 and the TrkA receptors are distributed in the dentate similarly to the septal input (Sobreviela et al, 1994;Dougherty and Milner, 1999;Barker-Gibb et al, 2001). The colocalization of p75 and TrkA in the septal fibers may be an important property dictating the probability of high-affinity binding (Hempstead et al, 1991;Esposito et al, 2001) and the consequent proliferation of cholinergic synapses.…”

Exercising Our Brains: How Physical Activity Impacts Synaptic Plasticity in the Dentate Gyrus

“…Until recently, this precursor of BDNF had been considered to be inactive; however, new evidence has suggested that pro-BDNF interacts with its own distinct receptor, the p75 neurotrophin receptor (p75 NTR ) (Lee et al 2001). p75 NTR is primarily localized on axons and axon terminals (Dougherty and Milner 1999), as well as dendritic spines in the CA1 region (Woo et al 2005) and has been implicated with numerous roles in the CNS, including apoptosis, axon elongation, and synaptic transmission (Dechant and Barde 2002). Recent evidence has proposed that p75 NTR , via pro-BDNF, may also affect synaptic plasticity.…”