Abstract
Estrogen interacts with N-methyl-D-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In hippocampus, estrogen increases both dendritic spine density and synapse number, and NMDA antagonists block these effects. Thus, estrogen-mediated hippocampal plasticity may be of particular importance in the context of age-related changes in endocrine status and cognitive performance. NR1 levels per synapse are increased in CA1 by estrogen in aged rats but not young rats, although no information is available on estrogen-induced synaptic alterations in other NMDA receptor subunits that might impact function. Therefore, the present study was designed to investigate the effect of estrogen on the synaptic and subsynaptic distributions of the NMDA receptor subunits, NR2A and NR2B in CA1 pyramidal cells, within the context of aging. Our results demonstrated that the overall synaptic levels of NR2A and NR2B are similar in young and aged female rats, regardless of estrogen treatment. However, in the aged CA1, estrogen restores NR2B levels back to young levels in the lateral portions of the active synaptic zone. Thus, estrogen may impact the mobility of NMDA receptors across the synapse and, in the process, restore a more youthful synaptic profile. These findings have important implications for the mechanism of estrogen-induced alterations in NMDA receptor-mediated processes, particularly in the context of aging.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 419-426 |
| Number of pages | 8 |
| Journal | Journal of Comparative Neurology |
| Volume | 474 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 28 2004 |
| Externally published | Yes |
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Keywords
- Electron microscopy
- Excitatory amino acids
- Glutamate receptor
- Hormone replacement
- Reproductive senescence
- Synapse
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Estrogen modulates synaptic N-methyl-D-aspartate receptor subunit distribution in the aged hippocampus. / Adams, Michelle M.; Fink, Susan E.; Janssen, William G M; Shah, Ravi A.; Morrison, John.
In: Journal of Comparative Neurology, Vol. 474, No. 3, 28.06.2004, p. 419-426.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Estrogen modulates synaptic N-methyl-D-aspartate receptor subunit distribution in the aged hippocampus
AU - Adams, Michelle M.
AU - Fink, Susan E.
AU - Janssen, William G M
AU - Shah, Ravi A.
AU - Morrison, John
PY - 2004/6/28
Y1 - 2004/6/28
N2 - Estrogen interacts with N-methyl-D-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In hippocampus, estrogen increases both dendritic spine density and synapse number, and NMDA antagonists block these effects. Thus, estrogen-mediated hippocampal plasticity may be of particular importance in the context of age-related changes in endocrine status and cognitive performance. NR1 levels per synapse are increased in CA1 by estrogen in aged rats but not young rats, although no information is available on estrogen-induced synaptic alterations in other NMDA receptor subunits that might impact function. Therefore, the present study was designed to investigate the effect of estrogen on the synaptic and subsynaptic distributions of the NMDA receptor subunits, NR2A and NR2B in CA1 pyramidal cells, within the context of aging. Our results demonstrated that the overall synaptic levels of NR2A and NR2B are similar in young and aged female rats, regardless of estrogen treatment. However, in the aged CA1, estrogen restores NR2B levels back to young levels in the lateral portions of the active synaptic zone. Thus, estrogen may impact the mobility of NMDA receptors across the synapse and, in the process, restore a more youthful synaptic profile. These findings have important implications for the mechanism of estrogen-induced alterations in NMDA receptor-mediated processes, particularly in the context of aging.
AB - Estrogen interacts with N-methyl-D-aspartate (NMDA) receptors to regulate multiple aspects of morphological and functional plasticity. In hippocampus, estrogen increases both dendritic spine density and synapse number, and NMDA antagonists block these effects. Thus, estrogen-mediated hippocampal plasticity may be of particular importance in the context of age-related changes in endocrine status and cognitive performance. NR1 levels per synapse are increased in CA1 by estrogen in aged rats but not young rats, although no information is available on estrogen-induced synaptic alterations in other NMDA receptor subunits that might impact function. Therefore, the present study was designed to investigate the effect of estrogen on the synaptic and subsynaptic distributions of the NMDA receptor subunits, NR2A and NR2B in CA1 pyramidal cells, within the context of aging. Our results demonstrated that the overall synaptic levels of NR2A and NR2B are similar in young and aged female rats, regardless of estrogen treatment. However, in the aged CA1, estrogen restores NR2B levels back to young levels in the lateral portions of the active synaptic zone. Thus, estrogen may impact the mobility of NMDA receptors across the synapse and, in the process, restore a more youthful synaptic profile. These findings have important implications for the mechanism of estrogen-induced alterations in NMDA receptor-mediated processes, particularly in the context of aging.
KW - Electron microscopy
KW - Excitatory amino acids
KW - Glutamate receptor
KW - Hormone replacement
KW - Reproductive senescence
KW - Synapse
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UR - http://www.scopus.com/inward/citedby.url?scp=2642562084&partnerID=8YFLogxK
U2 - 10.1002/cne.20148
DO - 10.1002/cne.20148
M3 - Article
VL - 474
SP - 419
EP - 426
JO - Journal of Comparative Neurology
JF - Journal of Comparative Neurology
SN - 0021-9967
IS - 3
ER -