Showing papers by "Bruce S. McEwen published in 1994"
TL;DR: These effects on behavior parallel the reversible stress-induced atrophy of dendrites of hippocampal CA3 neurons that are also blocked by the drugs.
775 citations
TL;DR: It is concluded that estradiol exerts its effect on hippocampal dendritic spine density via a mechanism requiring activation specifically of NMDA receptors.
Abstract: In the adult female rat, the densities of dendritic spines and synapses on hippocampal CA1 pyramidal cells are dependent upon the ovarian steroid estradiol; moreover, spine and synapse density fluctuate naturally as ovarian steroid levels vary across the estrous cycle. To determine whether the effects of estradiol on dendritic spine density require activation of specific neurotransmitter systems, we have treated animals concurrently with estradiol and one of four selective neurotransmitter receptor antagonists: MK 801, a noncompetitive NMDA receptor antagonist; CGP 43487, a competitive NMDA receptor antagonist; NBQX, an AMPA receptor antagonist; or scopolamine, a muscarinic receptor antagonist. Our results indicate that the effects of estradiol can be blocked by treatment with either of the NMDA receptor antagonists, but treatment with an AMPA or muscarinic receptor antagonist has no effect on spine density. Thus, we have concluded that estradiol exerts its effect on hippocampal dendritic spine density via a mechanism requiring activation specifically of NMDA receptors.
665 citations
TL;DR: It is suggested that increases in corticotropin-releasing hormone, by stress or glucocorticoids, in the amygdala may have functional consequences for allostatic load.
325 citations
TL;DR: In the adult female rat brain, dendrites of neurons in the ventromedial hypothalamus and CA1 region of the hippocampus sprout increased numbers of spines on dendrite and then lose them during the 4- or 5-day estrous cycle, and the changes of synaptic density in the hypothalamus are responsible for the cyclicity of sexual behavior.
303 citations
TL;DR: To determine whether excitatory input plays a role in the regulation of cell birth and survival in the developing granule cell layers and their germinal regions, the subependymal layer and hilus, rat pups were treated with the N‐methyl D‐aspartate (NMDA) receptor antagonists MK‐801, CGP 37849, or CGP 43487 during the first postnatal week.
Abstract: Excitatory input regulates cell birth and survival in many systems. The granule cell population of the rat dentate gyrus is formed primarily during the postnatal period. Excitatory afferents enter the dentate gyrus and begin to form synapses with granule cells during the first postnatal week, the time of maximal cell birth and death. In order to determine whether excitatory input plays a role in the regulation of cell birth and survival in the developing granule cell layers and their germinal regions, the subependymal layer and hilus, we treated rat pups with the N-methyl D-aspartate (NMDA) receptor antagonists MK-801, CGP 37849, or CGP 43487 during the first postnatal week and examined the numbers of 3H-thymidine-labeled cells, pyknotic cells, and healthy cells in these regions. In order to determine the cell type that was affected, sections from brains of MK-801-treated rats were processed for 3H-thymidine autoradiography combined with immunohistochemistry for the marker of radial glia, vimentin, and the marker of mature astrocytes, glial fibrillary acidic protein (GFAP). Within the dentate gyrus, NMDA receptor blockade resulted in the following changes: (1) the density of 3H-thymidine-labeled cells was increased, (2) the density of pyknotic cells was increased, (3) the density of 3H-thymidine-labeled pyknotic cells was increased, and (4) the density of healthy cells was decreased. The infrapyramidal blade/hilus showed changes throughout its extent, whereas the suprapyramidal blade showed changes only at the rostral level. No change in the numbers of 3H-thymidine-labeled vimentin-immunoreactive or GFAP-immunoreactive cells was observed in the dentate gyrus with MK-801 treatment, indicating that glia are not primarily affected by NMDA receptor blockade. Blockade of NMDA receptors resulted in gross morphologic changes in the dentate gyrus; in most cases, the infrapyramidal blade was indistinguishable from the hilus. Moreover, in several brains of animals treated with CGP 37849 or CGP 43487 on postnatal day (P)5, an abnormal aggregation of cells was observed ventral to the normal location of the infrapyramidal blade. This cellular cluster contained many pyknotic and 3H-thymidine-labeled cells and may represent cells that normally comprise the infrapyramidal blade. Dramatic changes to the subependymal layer were also seen following NMDA receptor blockade. The cross-sectional area of this region was significantly increased with MK-801, CGP 37849, or CGP 43487 treatment and contained a high density of 3H-thymidine-labeled cells and 3H-thymidine-labeled pyknotic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
254 citations
TL;DR: The results suggest that the endocrine system plays a role in the regulation of immune cell turnover and/or redistribution between immune compartments under conditions of normal daily experiences, namely, the diurnal cycle, and mild acute stress.
Abstract: In this study, we examined hormonal regulation of the distribution profiles of leukocyte subpopulations in the peripheral blood of rats. Flow cytometric analysis revealed significant and selective changes in the numbers and the percentages of peripheral blood leukocyte subpopulations which were a function of diurnal variations in hormone secretion and hormonal changes induced by acute stress. Changes in numbers and percentages of leukocyte subpopulations, which varied with time of day, were similar to changes observed under stress conditions. At the beginning of the rat's active period, and after 1 h of restraint stress, there was a significant reduction in numbers of leukocytes and lymphocytes. This reduction was primarily accounted for by a decrease in numbers of B cells, natural killer cells, monocytes (diurnal study), and helper T cells (diurnal study). There was also a significant decrease in the percentage of lymphocytes which was mirrored by an increase in the percentage of neutrophils in the peripheral blood. Peripheral blood leukocyte numbers were inversely related to plasma corticosterone levels. These results suggest that the endocrine system plays a role in the regulation of immune cell turnover and/or redistribution between immune compartments under conditions of normal daily experiences, namely, the diurnal cycle, and mild acute stress. They also suggest that these effects are selective for certain subpopulations of leukocytes.
249 citations
TL;DR: The present review concerns itself with four major neuropeptide systems--enkephalin, dynorphin, tachykinins and neurotensin--and it summarizes neuroanatomical and functional studies as well as emphasizing regulatory interactions between neurotransmitters and neuropepeptides at the level of neuropePTide gene expression.
219 citations
TL;DR: Evidence is reviewed in this article that a number of steroid actions in the hippocampus involves the co-participation of excitatory amino acids, which point to a high degree of interdependency between certain neurotransmitters and the actions of steroid hormones.
159 citations
TL;DR: Repeated restraint stress produced habituation to acute restraint stress, but not to acute shaking stress, in PVN, raphe and central gray, and in LC, repeated restraint stress caused some habituated to both acute stressors.
Abstract: Acute restraint and shaking stress each induced the mRNA for the immediate early gene (IEG), c-fos, within 1 h in locus coeruleus (LC), midbrain raphe nuclei and central gray. Both acute restraint stress and acute shaking stress activated c-fos and zif/268 mRNA in paraventricular nuclei within 1 h. Midbrain A9 and A10 dopaminergic neurons did not show any c-fos or zif/268 mRNA induction by either acute stressor. Repeated restraint stress (14d, 1h/d) produced habituation to acute restraint stress, but not to acute shaking stress, in PVN, raphe and central gray. In LC, repeated restraint stress caused some habituation to both acute stressors.
107 citations
TL;DR: It is demonstrated that a cyclic regimen of estradiol replacement in ovariectomized rats is sufficient to enhance the satiating effect of exogenous CCK-8 and that simultaneous progesterone treatment does not influence this effect.
104 citations
TL;DR: In this study, in situ hybridization is used to investigate the adrenal steroid regulation of the mRNAs encoding the neurotrophic factors BDNF, NT-3, and bFGF, their respective receptors, and the growth-associated protein GAP-43.
TL;DR: The results suggest that the LC may have protective effects on SN dopaminergic neurons.
TL;DR: Results show that adrenalectomy (ADX), which caused a decline in CORT to levels < 0.3 micrograms %, has generally little impact on the hypothalamic NPY projection system under normal, basal conditions, and evidence obtained from CORT replacement in ADX rats shows that this steroid has profound impact on all components of the hypothalamate NPY system.
TL;DR: The effects of adrenalectomy and replacement with glucocorticoid receptor agonists on serotonin (5-HT) 5- HT1A and 5-HT2 receptor binding in rat brain were evaluated and the expression of 5-ht transporter mRNA was unchanged in the raphe nucleus as measured by in situ hybridization.
TL;DR: Quantitative autoradiography was used to assess alterations in serotonin (5-HT) receptor binding in the hypothalamus and hippocampus following denervation with 5,7-dihydroxytryptamine, ovariectomy (OVX) and gonadal steroid manipulation, and the relationship of these results to the role of 5-HT in mediating lordosis behavior is discussed.
Abstract: Quantitative autoradiography was used to assess alterations in serotonin (5-HT) receptor binding in the hypothalamus and hippocampus following denervation with 5, 7-dihydroxytryptamine (5, 7-DHT), ova
TL;DR: The recovery of accessory adrenal tissue in ADX rats, as indicated by the low levels of Cort, appears sufficient to suppress dentate granule neuron pyknosis, but may not be sufficient to suppressing salt appetite.
TL;DR: Repeated stress, acting through excitatory amino acids released from mossy fiber terminals and elevated adrenal steroid blood levels causes atrophy of dendrites of hippocampal CA3 pyramidal neurons, which may be indicative of the beginning of damage or represent a short-term protective mechanism to avoid greater damage.
TL;DR: Effects of adrenal steroids on immune cell distribution are dependent on the receptor subtype involved as well as the specific cell type targeted, which allows for varied and complex effects of adrenals on the immune system under physiological conditions.
Abstract: Adrenal steroids exert their effects through two distinct adrenal steroid receptor subtypes; the high affinity type I, or mineralocorticoid, receptor and the lower affinity type II, or glucocorticoid, receptor. Adrenal steroids have well known effects on immune cell distribution, and although both type I and II receptors are expressed in immune cells and tissues, few data exist on the relative effects mediated through these two receptor subtypes. Accordingly, we administered selective type I and II adrenal steroid receptor agonists to young adult male Sprague-Dawley rats for 7 days and then measured immune cell distribution in the peripheral blood and spleen. Results were compared with those of similar studies using the naturally occurring glucocorticoid of the rat, corticosterone, which binds both type I and II receptors. The majority of the well characterized effects of adrenal steroids on peripheral blood immune cells (increased neutrophils and decreased lymphocytes and monocytes) were reproduced by th...
TL;DR: It is demonstrated that aldosterone both enhances and prolongs hippocampal plasticity in freely behaving rats.
Abstract: The effects of Type I adrenal steroid receptors in prolonging synaptic plasticity in the dentate gyrus of freely behaving rats was investigated. Rats were implanted with chronic, bilateral stimulating and recording electrodes in the perforant pathway and dentate gyrus, respectively, and adrenalectomized (ADX). After a 2-3 day recovery period, baseline recordings of field potentials were made followed by administration of aldosterone or vehicle. One hour later, high frequency stimulation (HFS; chosen to produce comparable long-term potentiation (LTP) in the aldosterone-treated and control groups) was applied unilaterally and recording was continued for 1 h and again performed at 3, 24 and 48 h. LTP in ADX controls decayed significantly within 3 h, and returned to baseline levels at 24 h. In contrast, the aldosterone-treated animals showed enhanced LTP at 3, 24 and 48 h. These findings demonstrate that aldosterone both enhances and prolongs hippocampal plasticity.
TL;DR: The hippocampus responds to adrenal steroids as well and undergoes changes in dendritic branching as a result of repeated stress, and implications of hormonally directed changes in brain structure and neurochemistry are discussed with respect to human pathophysiology.
Abstract: Gonadal and adrenal hormones regulate both structure and neurochemical function in neurons that express receptors for them. Gonadal hormone effects mediate sexual differentiation of the brain and reproductive tract, and their actions during early development program groups of cells in the nervous system to respond in male- or female-typical ways to hormones in adulthood. Induction of synapse formation is one consequences of brain sexual differentiation, but hormonally directed synaptic plasticity is by no means confined to early development and in fact occurs cyclically during reproductive cycles in a number of brain regions of the female rat, including the hippocampus. The hippocampus responds to adrenal steroids as well and undergoes changes in dendritic branching as a result of repeated stress. Implications of hormonally directed changes in brain structure and neurochemistry are discussed with respect to human pathophysiology.
TL;DR: Data support the conclusion that corticosteroids can modulate hippocampal excitability through the site-specific regulation of the expression of specific GABAA receptor subunits.
TL;DR: In agreement with previous reports, adrenal steroid regulation of AVP and CRH mRNA was found to be mediated primarily through the Type II receptor.
TL;DR: Tianeptine significantly reduced both the expression of serotonin transporter mRNA and serotonin transporter binding sites labeled by [3H]paroxetine in rat dorsal raphe nucleus, and this effect, which is similar to a reported effect for serotonin reuptake inhibitors, may help to explain the antidepressant effect of tianeptines.
TL;DR: The results suggest that hormonal factors regulate calmodulin gene expression in adult brain, and further evidence is required to establish the temporal interrelationships between steroid regulation of cal modulin and its target proteins.
TL;DR: Monitoring of hippocampal expression of APP695 mRNA by in situ hybridization, with aging and with steroid manipulation found an increase in hippocampal APP695 expression compared to untreated, ovariectomized controls.
Abstract: In the rat hippocampus, neuronal morphology and survival are profoundly affected by adrenal steroids, and synaptic plasticity can be modulated by the ovarian sex steroids estrogen and progesterone. beta-amyloid peptides, which accumulate in neuritic plaques and are derived from the amyloid precursor protein (APP), have been shown to be both trophic and toxic for hippocampal neurons. Of the various APP isoforms, APP695 is the predominant form found in rat brain and the APP695 mRNA is abundantly expressed in the hippocampus. In order to investigate the hypothesis that APP may serve as a mediator of the steroid effects, we have monitored the hippocampal expression of APP695 mRNA by in situ hybridization, with aging and with steroid manipulation. In aged female rats we observed a decrease in the level of APP695 mRNA relative to young female rats, while no such age difference was evident in male rats. Physiological, surgical and pharmacological manipulation of glucocorticoids appeared to have no effect on APP695 mRNA levels in the hippocampus. Treatment of young, ovariectomized female rats with estrogen and progesterone, resulted in an increase in hippocampal APP695 expression compared to untreated, ovariectomized controls.
TL;DR: The chapter discusses the interactive roles that are played by thyroid hormone balance, sex hormones, and gender, together with the actions of adrenal steroids, in determining the ability of the hippocampus to change its structure and function in response to the external environment.
Abstract: Publisher Summary This chapter discusses the significance of adrenal steroid action on the hippocampus. The first effects of adrenal steroids concerned destruction of neural tissue, but later findings pointed to the additional effects that protect neurons and enhance plasticity. The role of the hippocampus in learning and memory processes may be subject to regulation by circulating adrenal steroids over both short and long time periods. The adult hippocampus is the site of hormonally directed plasticity. Estradiol and progesterone regulate the cyclic formation and breakdown of excitatory synapses on CA1 pyramidal neurons. Excess thyroid hormone promotes a reduction in dendritic spines on CA1 pyramidal neurons, whereas the transient elevation of thyroid hormone neonatally produces a long-term increase of dendritic branching and spine density in the CA3 region of the hippocampal formation. The chapter discusses the interactive roles that are played by thyroid hormone balance, sex hormones, and gender, together with the actions of adrenal steroids, in determining the ability of the hippocampus to change its structure and function in response to the external environment.
TL;DR: In situ hybridization experiments revealed that a major site of VIP mRNA expression in the hypothalamus is the suprachiasmatic nucleus, and adrenalectomy resulted in an approximate decrease by half in VIP transcripts in this nucleus, suggesting that VIP mRNA may be regulated by indirect mechanisms, influenced by the adrenal gland.
TL;DR: Analysis of frequency histograms suggests that glucocorticoids promote in a few regions (AL, POA MED, CA2 subfield) a coordinate increase in the biosynthesis of the α3 and β1-subunit mRNA.
TL;DR: The studies suggest that the effects of ADX on calmodulin-dependent adenylate cyclase may occur through a reduction in the absolute amount of the catalytic subunit or an alteration(s) in the efficiency of coupling between adnylatecyclase and its modulators.
Abstract: Ca2+/calmodulin-dependent processes are altered by manipulations of the hypothalamic-pituitary-adrenal axis. In particular, adrenalectomy (ADX) attenuates hippocampal, but not cortical, calmodulin-dependent adenylate cyclase activity measured during the active (waking) phase of rats. The involvement of calmodulin- and guanine nucleotide (G)-binding proteins in the effects of ADX on the activity of calmodulin-dependent adenylate cyclase were investigated. In hippocampal membranes, inclusion of the GTP antagonist guanosine 5'-O-(2-thiodiphosphate) (250 microM) caused pronounced inhibition of calmodulin-stimulated adenylate cyclase activity. Guanosine 5(1)-O-(2-thiodiphosphate) had much smaller effects on calmodulin-independent (basal and forskolin-stimulated) enzyme activity. Substitution of Mn2+ for Mg2+ in the assay medium increased basal and forskolin-stimulated adenylate cyclase activity, but abolished calmodulin-dependent activation of this enzyme in both hippocampal and cortical membranes. These treat...