Effects of estrogen and aging on the synaptic distribution of phosphorylated Akt-immunoreactivity in the CA1 region of the female rat hippocampus - PubMed (original) (raw)

Comparative Study

Effects of estrogen and aging on the synaptic distribution of phosphorylated Akt-immunoreactivity in the CA1 region of the female rat hippocampus

Murat Yildirim et al. Brain Res. 2011.

Abstract

The estrogen 17β-estradiol (E) increases the axospinous synaptic density and plasticity in the hippocampal CA1 region of young female rats but fails to do so in aged female rats. This E stimulus on synaptic plasticity is associated with the phosphorylation-dependent activation of Akt kinase. Our previous findings demonstrated that increased estrogen levels subsequently increase phosphorylated Akt (pAkt)-immunoreactivity (-IR) within the dendritic shafts and spines of pyramidal neurons in young female rats. Therefore, because Akt can promote cell survival and growth, we tested the hypothesis that the less plastic synapses of aged female rats would contain less E-stimulated pAkt-IR. Here, young (3-4 months) and aged (22-23 months) female rats were ovariectomized 7 days prior to a 48-h administration of either vehicle or E. The pAkt-IR synaptic distribution was then analyzed using post-embedding electron microscopy. In both young and aged rats, pAkt-IR was found in dendritic spines and terminals, and pAkt-IR was particularly abundant at the post-synaptic density. Quantitative analyses revealed that the percentage of pAkt-labeled synapses was significantly greater in young rats compared to aged rats. Nonetheless, E treatment significantly increased pAkt-IR in pre- and post-synaptic profiles of both young and aged rats, although the stimulus in young rats was notably more widespread. These data support the evidence that hormone-activated signaling associated with cell growth and survival is diminished in the aged brain. However, the observation that E can still increase pAkt-IR in aged synapses presents this signaling component as a candidate target for hormone replacement therapies.

Copyright © 2010. Published by Elsevier B.V.

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Figures

Fig. 1

Fig. 1

Representative electron micrographs show the distribution of pAkt-IR (black particles) in the CA1 stratum radiatum of young OVX + estrogen (E) (A), young OVX + vehicle (B), aged OVX + E (C) and aged OVX + vehicle (D) rats. t, terminal; sp, dendritic spine. Bar, 100 nm.

Fig. 2

Fig. 2

The overall percentage of pAkt immunoreactive axospinous synapses is significantly decreased in aged OVX rats compared to young OVX rats and significantly increased following E-replacement in both young and aged OVX rats. *p < 0.02.

Fig. 3

Fig. 3

Schematic drawing showing the eight bin divisions of a pre- and post-synaptic profile.

Fig 4

Fig 4

Both age and estrogen altered the subcellular distribution of pAkt immunogold particles in pre- and post-synaptic profiles in the CA1 stratum radiatum region. A. In young OVX rats, E administration significantly increased the number of pAkt immunogold particles in all synaptic bins except 6 and 7 (although there was a tends in bin 7, p = 0.05). B. In aged OVX rats, E administration significantly increased the number of pAkt immunogold particles only in bins 1, 2 and 6. Moreover, E administration to aged OVX animals significantly decreased the number of pAkt immunogold particles in bin 4. *p < 0.05

Fig. 5

Fig. 5

Schematic diagram showing the effects of age and estrogen replacement on the distribution of pAkt in synaptic complexes of the female rat stratum radiatum CA1 region. Synaptic complexes from young OVX rats have more pAkt-IR, especially in the post-synaptic region compared to aged OVX rats. Following E treatment, pAkt-IR is increased in synaptic complexes in both young and aged OVX rats, although the stimulus in young rats is more widespread.

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