G-protein-coupled estrogen receptor 1 is anatomically positioned to modulate synaptic plasticity in the mouse hippocampus.

Both estrous cycle and sex affect the numbers and types of neuronal and glial profiles containing the classical estrogen receptors α and β, and synaptic levels in the rodent dorsal hippocampus. Here, we examined whether the membrane estrogen receptor, G-protein-coupled estrogen receptor 1 (GPER1), is anatomically positioned in the dorsal hippocampus of mice to regulate synaptic plasticity. By light microscopy, GPER1-immunoreactivity (IR) was most noticeable in the pyramidal cell layer and interspersed interneurons, especially those in the hilus of the dentate gyrus.

Post-synaptic density-95 (PSD-95) binding capacity of G-protein-coupled receptor 30 (GPR30), an estrogen receptor that can be identified in hippocampal dendritic spines.

The estrogen 17β-estradiol (E2) modulates dendritic spine plasticity in the cornu ammonis 1 (CA1) region of the hippocampus, and GPR30 (G-protein coupled estrogen receptor 1 (GPER1)) is an estrogen-sensitive G-protein-coupled receptor (GPCR) that is expressed in the mammalian brain and in specific subregions that are responsive to E2, including the hippocampus. The subcellular localization of hippocampal GPR30, however, remains unclear. Here, we demonstrate that GPR30 immunoreactivity is detected in dendritic spines of rat CA1 hippocampal neurons in vivo and that GPR30 protein can be found in rat brain synaptosomes.

Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms.

From its origins in how the brain controls the endocrine system via the hypothalamus and pituitary gland, neuroendocrinology has evolved into a science that now includes hormone action on many aspects of brain function. These actions involve the whole central nervous system and not just the hypothalamus. Advances in our understanding of cellular and molecular actions of steroid hormones have gone beyond the important cell nuclear actions of steroid hormone receptors to include signaling pathways that intersect with other mediators such as neurotransmitters and neuromodulators.

Ovarian hormones influence corticotropin releasing factor receptor colocalization with delta opioid receptors in CA1 pyramidal cell dendrites.

Stress interacts with addictive processes to increase drug use, drug seeking, and relapse. The hippocampal formation (HF) is an important site at which stress circuits and endogenous opioid systems intersect and likely plays a critical role in the interaction between stress and drug addiction. Our prior studies demonstrate that the stress-related neuropeptide corticotropin-releasing factor (CRF) and the delta-opioid receptor (DOR) colocalize in interneuron populations in the hilus of the dentate gyrus and stratum oriens of CA1 and CA3.

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

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.

LIM kinase mediates estrogen action on the actin depolymerization factor Cofilin.

The ovarian hormone estrogen increases the axospinous synapse density in the hippocampal CA1 region of young female rats but fails to do so in aged rats. This estrogen-mediated alteration of spine synapse structures suggests the coincident requirement for the structural reorganization of the underlying actin cytoskeleton network. Actin reorganization is known to require the deactivation of Cofilin, an actin depolymerization factor.

Effects of acute diuresis stress on egr-1 (zif268) mRNA levels in brain regions associated with motivated behavior.

Stressors evoke a well-studied physiological stress-response, namely, an immediate systemic release of catecholamines from the adrenals followed shortly afterwards by the release of adrenal steroids. The intensity of that response can often be inferred by the amount of adrenal steroids released into the circulatory system. It is still unclear however how the intensity and duration of the stressor affect a number of brain regions, including those in the motivational system.

Thinking outside the pyramidal cell: unexplored contributions of interneurons and neuropeptide Y to estrogen-induced synapse formation in the hippocampus.

Since the first finding that 17beta-estradiol (E) can regulate CA1 pyramidal cell synapse formation, subsequent studies have explored many potential E-dependent mechanisms occurring within CA1 pyramidal cells. Fewer studies have focused on E-dependent processes outside of the pyramidal cell that may influence events activity of the pyramidal cells. This review considers hippocampal interneurons, which can potently regulate the excitability of simultaneously firing pyramidal cells.

Gene therapy to bet on: protecting neurons from stress hormones.

Glucocorticoids are adrenal steroid 'stress' hormones that are important in normal brain function. However, during conditions of excitotoxic injury to neurons, glucocorticoids can exacerbate cell death. A recent study has developed a 'trifecta' of ingenious viral vector-based approaches to modify the neuronal stress response and to diminish this exacerbation both in vitro and in vivo.

Estrogen and ovariectomy regulate mRNA and protein of glutamic acid decarboxylases and cation-chloride cotransporters in the adult rat hippocampus.

17beta-Estradiol spatiotemporally regulates the gamma-aminobutyric acid (GABAergic) tone in the adult hippocampus. However, the complex estrogenic effect on the GABAergic system is still unclear. In adult central nervous system (CNS) neurons, GABA can induce both inhibitory and excitatory actions, which are predominantly controlled by the cation-chloride cotransporters NKCC1 and KCC2.

Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.

In addition to genomic pathways, estrogens may regulate gene expression by activating specific signal transduction pathways, such as that involving phosphatidylinositol 3-kinase (PI3-K) and the subsequent phosphorylation of Akt (protein kinase B). The Akt pathway regulates various cellular events, including the initiation of protein synthesis. Our previous studies showed that synaptogenesis in hippocampal CA1 pyramidal cell dendritic spines is highest when brain estrogen levels are highest.

Estrogen stimulates postsynaptic density-95 rapid protein synthesis via the Akt/protein kinase B pathway.

Estrogens induce synaptogenesis in the CA1 region of the dorsal hippocampus during the estrous cycle of the female rat. Functional consequences of such estrogen-mediated synaptogenesis include cyclic changes in neurotransmission and memory. At the molecular level, estrogen stimulates the rapid activation of specific signal transduction pathways, and of particular interest is the activation of Akt (protein kinase B), a key signal transduction intermediate that initiates protein translation by alleviating the downstream translational repression of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1).

Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat.

Tachykinins are a family of neuropeptides that inhibit salt appetite. Although decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats, no decrease is seen in natriorexic sodium-replete rats that are administered the aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis of tachykinins could not account for increased appetite, we hypothesized that increased salt appetite was due to a downregulation of tachykinin receptors.