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E Gould

Publications and source records attributed to E Gould.

At least 19 recordsLinked to original sources
PubMed1997

Activation of the type 2 adrenal steroid receptor can rescue granule cells from death during development.

To determine whether activation of the type 2 adrenal steroid receptor affects granule cell death in the developing dentate gyrus, we treated rat pups with the type 2 receptor agonist RU28362 and examined degenerating cells using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and Nissl staining. RU28362 administration decreased the numbers of degenerating granule cells suggesting that type 2 receptor activation can rescue granule cells from degeneration.

Adrenal Cortex Hormones↗
PubMed1997

Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMDA receptor activation.

These studies were designed to determine whether adult neurogenesis occurs in the dentate gyrus of the tree shrew, an animal phylogenetically between insectivores and primates, and to explore the possibility that this process is regulated by stressful experiences and NMDA receptor activation. We performed immunohistochemistry for cell-specific markers and the thymidine analog bromodeoxyuridine (BrdU), a marker of DNA synthesis that labels proliferating cells and their progeny, on the brains of adult tree shrews subjected to psychosocial stress or NMDA receptor antagonist treatment. Cells that incorporated BrdU in the dentate gyrus of adult tree shrews were primarily located in the subgranular zone, had morphological characteristics of granule neuron precursors, and appeared to divide within 24 hr after BrdU injection. Three weeks after BrdU injection, BrdU-labeled cells had neuronal morphology, expressed the neuronal marker neuron specific enolase, and were incorporated into the granule cell layer. Vimentin-immunoreactive radial glia were observed in the dentate gyrus with cell bodies in the subgranular zone and processes extending into the granule cell layer. Exposure to acute psychosocial stress resulted in a rapid decrease in the number of BrdU-labeled cells in the dentate gyrus. In contrast, blockade of NMDA receptors, with the NMDA receptor antagonist MK-801, resulted in an increase in the number of BrdU-labeled cells in the dentate gyrus. These results indicate that adult neurogenesis occurs in the tree shrew dentate gyrus and is regulated by a stressful experience and NMDA receptor activation. Furthermore, we suggest that these characteristics may be common to most mammalian species.

Aging↗
PubMed1997

Early NMDA receptor blockade impairs defensive behavior and increases cell proliferation in the dentate gyrus of developing rats.

These studies were conducted to determine whether (a) early N-methyl-D-aspartate (NMDA) receptor blockade impairs defensive behavior and (b) a relationship exists between defensive behavior and the production of granule cells in the dentate gyrus. Rat pups were treated with different doses of the NMDA receptor antagonist CGP 43487 on postnatal day (P) 5, and their behavior was observed following exposure to an unfamiliar adult male rat, a potential predator, on P13, P20, and P30. A dose-dependent impairment in freezing behavior was observed in rat pups treated with NMDA receptor antagonist on P13, P20, but not P30. Moreover, a dose-dependent increase in the number of (3)H-thymidine-labeled cells in the dentate gyrus was detected following CGP 43487 treatment, suggesting that an inverse relationship exists between cell proliferation and freezing behavior in rat pups following NMDA receptor blockade.

2-Amino-5-phosphonovalerate↗
PubMed1996

Distinct populations of cells in the adult dentate gyrus undergo mitosis or apoptosis in response to adrenalectomy.

Granule neurons of the rat dentate gyrus are born in adulthood as well as during development. Apoptotic cell death also occurs normally in this population throughout the life of the rat. Removal of adrenal steroids results in both increased production and increased degeneration of dentate gyrus granule cells. In order to determine whether the age of a cell affects its response to adrenalectomy (ADX), the numbers of dentate gyrus cells of different ages were assessed following ADX or sham operation. Older cells, i.e., those labeled with the thymidine analog bromodeoxyuridine (BrdU) on postnatal day (P) 6, were reduced in number following ADX on P60, and some had the morphologic characteristics of degenerating cells, indicating that significant numbers of mature cells die in response to ADX. In contrast, the number of younger cells, labeled with 3H-thymidine or BrdU in adulthood, 24 hours or 2 weeks before ADX, did not decrease, suggesting that these less mature cells do not die following ADX. An increase in the number of cells that are immunoreactive for proliferating cell nuclear antigen, a marker of dividing or recently mitotic cells, indicates that immature dentate gyrus cells divide following ADX. These results suggest that following ADX, mature cells born during the 1st postnatal week die, whereas immature cells divide.

Adrenal Glands↗
PubMed1996

Regulation of neuronal birth, migration and death in the rat dentate gyrus.

The granule cell population of the rat dentate gyrus forms over an extended period which begins during gestation and continues into adulthood. During the embryonic period, the postnatal period and in adulthood, granule cells proliferate, migrate and degenerate. We have found that granule cell production is dependent on the levels of circulating adrenal steroids and NMDA receptor-mediated excitatory input throughout life. In general, increases in adrenal steroid levels or NMDA receptor activation diminish the rate of cell proliferation whereas decreases in adrenal steroid levels or NMDA receptor activation increase the rate of cell production. This paper describes the regulation of granule cell proliferation, migration and survival by adrenal steroids and excitatory input and presents evidence that these factors may affect dentate gyrus-mediated behaviors.

Adrenal Cortex Hormones↗
PubMed1995

Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes.

Oestrogens have numerous effects on the brain, beginning during gestation and continuing on into adulthood. Many of these actions involve areas of the brain that are not primarily involved in reproduction, such as the basal forebrain, hippocampus, caudate putamen, midbrain raphe and brainstem locus coeruleus. This paper describes three actions of oestrogens that are especially relevant to brain mechanisms involved in memory processes and their alterations during ageing and neurodegenerative diseases: (1) the regulation of cholinergic neurons by oestradiol in the rat basal forebrain, involving induction of choline acetyltransferase and acetylcholinesterase according to a sexually dimorphic pattern; (2) the regulation of synaptogenesis in the CA1 region of the hippocampus by oestrogens and progestins during the four- to five-day oestrus cycle of the female rat. Formation of new excitatory synapses is induced by oestradiol and involves N-methyl-D-aspartate receptors; removal of these synapses involves intracellular progestin receptors; (3) sex differences in hippocampal structure, which may help to explain differences in the strategies that male and female rats use to solve spatial navigation problems. During the period of development when testosterone is elevated in the male, aromatase and oestrogen receptors are also elevated, making it likely that this pathway is involved in the masculinization of hippocampal structure.

Aging↗
PubMed1995

Persistence and transmission of tick-borne viruses: Ixodes ricinus and louping-ill virus in red grouse populations.

The population dynamics of tick-borne disease agents and in particular the mechanisms which influence their persistence are examined with reference to the flavivirus that causes louping-ill in red grouse and sheep. Pockets of infection cause heavy mortality and the infection probably persists as a consequence of immigration of susceptible hosts. Seroprevalence is positively associated with temporal variations in vectors per host, although variation between areas is associated with the abundance of mountain hares. The presence of alternative tick hosts, particularly large mammals, provides additional hosts for increasing tick abundance. Grouse alone can not support the vectors and the pathogen but both can persist when a non-viraemic mammalian host supports the tick population and a sufficiently high number of nymphs bite grouse. These alternative hosts may also amplify virus through non-viraemic transmission by the process of co-feeding, although the relative significance of this has yet to be determined. Another possible route of infection is through the ingestion of vectors when feeding or preening. Trans-ovarial transmission is a potentially important mechanism for virus persistence but has not been recorded with louping-ill and Ixodes ricinus. The influence of non-viraemic hosts, both in the multiplication of vectors and the amplification of virus through non-viraemic transmission are considered significant for virus persistence.

Animals↗
PubMed1995

Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus.

The effects of afferent input and N-methyl-D-aspartate (NMDA) receptor activation on neurogenesis were examined in an intact system, the rat dentate gyrus, where neurons are naturally born in the adult. In the adult dentate gyrus, activation of NMDA receptors rapidly decreased the number of cells synthesizing DNA, whereas blockade of NMDA receptors rapidly increased the number of cells in the S phase identified with 3H-thymidine. Acute treatment with NMDA receptor antagonists increased the birth of neurons and increased the overall density of neurons in the granule cell layer. Lesion of the entorhinal cortex, the main excitatory afferent population to the granule neurons, also increased the birth of cells in the dentate gyrus. These results suggest that adult neurogenesis in the dentate gyrus of the rat is altered by afferent input, via NMDA receptors, and may be regulated naturally by endogenous excitatory amino acids.

2-Amino-5-phosphonovalerate↗
PubMed1994

The effects of adrenal steroids and excitatory input on neuronal birth and survival.

The dentate gyrus of the rat forms in three developmental phases, each of which is characterized by neuronal birth, migration and death. Recent evidence indicates that adrenal steroids regulate neuronal birth, death, and possibly migration throughout the life of the animal. However, the observation that very few neuroblasts in the developing or adult dentate gyrus express adrenal steroid receptors suggests that the effects of adrenal steroid manipulations on neurogenesis are indirect. Additional evidence indicates that NMDA receptor activation regulates neuronal birth and death in this brain region presenting the possibility that adrenal steroids influence these processes through direct actions on excitatory afferents. Future studies will address this possibility.

Adrenal Cortex Hormones↗
PubMed1994

Effects of adrenalectomy on spatial memory performance and dentate gyrus morphology.

Adrenalectomy (ADX) causes neuronal degeneration and cell loss in the dentate gyrus (DG) of the hippocampus. Since chemical or mechanical lesions of the DG are associated with impairments of spatial memory in rats, the effects of ADX on radial arm maze performance were evaluated. During 15 trials, where all 8 arms of the maze were baited, ADX rats were significantly impaired compared to sham operated controls (Shams). These trials were conducted 21-42 days post-ADX. Following these trials, time delays were instituted between the 4th and 5th choices, and ADX rats continued to show impaired performance. Daily intake of 3% saline was monitored in all rats and serum corticosterone (Cort) was measured. Saline consumption (ml/day) was higher in the ADX group (16.9 +/- 1.6 in ADX vs. 1.3 +/- 0.3 in Shams) and was negatively correlated with Cort level. Serum Cort (% microgram) differed between groups (0.6 +/- 0.4 vs. 15.0 +/- 2.3) and was negatively correlated with a greater number of maze errors, a measure of impaired performance. Cross sectional DG area was not reduced in ADX rats, and pyknotic cell number did not differ significantly between ADX and Sham animals. Moreover, pyknotic cell counts did not correlate with behavioral measures. These results lead to two conclusions: First, 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 suppress salt appetite.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗
PubMed1994

Blockade of NMDA receptors increases cell death and birth in the developing rat dentate gyrus.

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)

2-Amino-5-phosphonovalerate↗
PubMed1994

Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus.

The dentate gyrus of the rat produces new granule neurons well into adulthood. In the adult, newly born granule neurons migrate from the hilus to the granule cell layer, receive synaptic input, extend axons into the mossy fiber pathway, and express a neuronal marker. No previous studies have identified factors that regulate neuronal birth in the adult dentate gyrus. In order to determine whether glucocorticoids control neurogenesis in the adult dentate gyrus, the effects of adrenal steroid manipulations on neuronal birth were assessed using [3H]thymidine autoradiography and immunohistochemistry for the neuronal marker neuron specific enolase. Acute treatment with corticosterone produced a significant decrease in the density of [3H]thymidine-labeled cells in the hilus of the dentate gyrus. In contrast, removal of endogenous adrenal steroids stimulated increased neuronal birth; adrenalectomy resulted in a significant increase in the number of neuron specific enolase-immunoreactive [3H]thymidine labeled cells in the granule cell layer compared to sham operation. Replacement of corticosterone to adrenalectomized rats after [3H]thymidine injection did not substantially alter the increase in neurogenesis observed following adrenalectomy, even though this replacement protects cells from adrenalectomy-induced cell death. These results indicate that the rate of neurogenesis in the dentate gyrus of the adult rat is dependent upon the levels of circulating adrenal steroids.

Adrenalectomy↗
PubMed1993

Adrenal steroid receptor immunoreactivity in cells born in the adult rat dentate gyrus.

Several lines of evidence indicate that cell birth in the adult rat dentate gyrus is regulated by adrenal steroids. The expression of adrenal steroid receptors by mitotic cells in the dentate gyrus would support the hypothesis that these hormones act directly on granule cell progenitors. We performed a survival time course of in vivo [3H]thymidine autoradiography combined with immunohistochemistry for mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) and found that very few [3H]thymidine labeled mitotic cells express these receptors. By 4 weeks following [3H]thymidine administration, the vast majority of [3H]thymidine labeled cells were immunoreactive for MR and GR. These results suggest that adrenal steroids do not act directly on granule cell progenitors in the adult rat dentate gyrus.

Animals↗
PubMed1993

Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat.

In order to determine whether newly born cells in the dentate gyrus of the adult rat express the neuronal marker, neuron-specific enolase, or the glial marker, glial fibrillary acidic protein, we performed combined immunohistochemistry and autoradiography on brains from adult rats perfused at various times ranging from 1 h to four weeks following [3H]thymidine administration. Light-microscopic examination revealed a negligible number of [3H]thymidine-labeled cells showing neuron-specific enolase immunoreactivity during mitosis. However, by two weeks after [3H]thymidine administration, a significant increase in the density of [3H]thymidine-labeled neuron-specific enolase-immunoreactive cells was detected. Three weeks following [3H]thymidine injection the majority of [3H]thymidine-labeled cells (> 70%) were immunoreactive for the neuronal marker. At the four-week time-point, [3H]thymidine-labeled neuron-specific enolase-immunoreactive cells were indistinguishable from neighboring granule cells. In contrast, glial fibrillary acidic protein immunoreactivity was observed in a small but significant number of [3H]thymidine cells at the 1-h time-point and the proportion of labeled cells that were immunoreactive for this cell marker did not increase with time. [3H]Thymidine-labeled cells that were immunoreactive for glial fibrillary acidic protein typically showed morphologic characteristics of radial glia at all time-points. At the 1-h time-point, the majority of [3H]thymidine-labeled cells were observed in the hilus (> 60%) with the remainder being located in the granule cell layer. However, with a four-week survival-time most [3H]thymidine-labeled cells (> 85%) were located in the granule cell layer. The majority of newly born cells in the adult dentate gyrus differentiate into neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗