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Biomedical subjects

E Gould

Publications and source records attributed to E Gould.

At least 37 records · Page 2Linked to original sources

The cognitive determinants of performance on the Austin Maze.

This study aimed to investigate which abilities are measured by the Austin Maze. One hundred and eight university students were administered a battery of eight neuropsychological tests including, the Austin Maze, the Tower of London, the Wisconsin Card Sort Test, Block Design, the Visual Spatial Learning Test, Digit Span Backwards, the Brown-Peterson Task and the Wide Range Achievement Test of Reading. Results indicated that visuospatial ability and memory both significantly contributed to performance on the Austin Maze, but differed in the degree to which they explained the performance depending on which measure of maze performance was employed. It appears that visuospatial ability is measured in early trials of the Austin Maze when individuals are orienting themselves to the path. In later trials individuals must call upon visuospatial memory to consolidate the details of the path. Executive function and working memory were not found to be significantly implicated in performance on the Austin Maze.

Adolescent↗

Learning enhances adult neurogenesis in the hippocampal formation.

Thousands of hippocampal neurons are born in adulthood, suggesting that new cells could be important for hippocampal function. To determine whether hippocampus-dependent learning affects adult-generated neurons, we examined the fate of new cells labeled with the thymidine analog bromodeoxyuridine following specific behavioral tasks. Here we report that the number of adult-generated neurons doubles in the rat dentate gyrus in response to training on associative learning tasks that require the hippocampus. In contrast, training on associative learning tasks that do not require the hippocampus did not alter the number of new cells. These findings indicate that adult-generated hippocampal neurons are specifically affected by, and potentially involved in, associative memory formation.

Animals↗

Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress.

Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys (Callithrix jacchus) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and approximately 80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience.

Animals↗

A study on the venom yield of venomous snake species from Argentina.

A study on the venom yield of snakes from Argentina over a three year period was carried out on adult specimens of Bothrops alternatus (n = 74); Bothrops neuwiedii (n = 127); Bothrops ammodytoides (n = 30); Bothrops moojeni (n = 14); Bothrops jararaca (n = 14); B. jararacussu (n = 6); Crotalus durissus terrificus (n = 120) and Micrurus spp. (n = 6) as well as with 12 specimens of newborn C. d. terrificus kept in captivity. While for each species there was a positive correlation between venom yield and number of snakes milked, the correlation with the snake's body weights after individual milkings was even better, suggesting that the size of the snakes is more important in determining the venom yield than the number of snakes milked or the specimen's sex. Individual milkings indicated that, in addition to the snake size, when the amount of venom is normalized per 100 g body weight there is a species specific difference in venom yield. It follows the order B. jararacussu > B. moojeni approximately = B. jararaca approximately = B. alternatus > B. neuwiedii> Micrurus spp approximately = B. ammodytoides> C. d. terrificus. Although the venom yield per 100 g body weight of newborn C. d. terrificus specimens is 2-fold higher than that of adults, no correlation was observed between venom yield and body weight.

Age Factors↗

Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway.

Adrenal steroids and N-methyl-D-aspartate receptor activation have both been shown to regulate the rate of proliferation of granule neuron progenitor cells in the dentate gyrus of adult rats [Cameron H. A. and Gould E. (1994) Neuroscience 61, 203-209; Cameron H. A. et al. (1995) J. Neurosci. 15, 46874692]. Parallels between the actions of these two factors suggest that they may regulate cell division through a common pathway. This hypothesis was tested by altering both of the factors simultaneously and determining whether the effects were additive. The results of this study demonstrate that alterations in N-methyl-D-aspartate receptor activation block the effects of corticosterone level on cell proliferation; N-methyl-D-aspartate blocks the adrenalectomy-induced increase in [3H]thymidine-labelled cell density in the dentate gyrus, whereas the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (MK-801) prevents the corticosterone-induced decrease in proliferating cells. This finding suggests that adrenal steroids and N-methyl-D-aspartate receptor activation regulate granule cell production in the adult rat dentate gyrus through a common pathway and that N-methyl-D-aspartate receptor activation operates downstream of corticosterone in this pathway.

Adrenal Cortex Hormones↗

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↗

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↗

Lesion-induced proliferation of neuronal progenitors in the dentate gyrus of the adult rat.

In order to determine whether granule cell death stimulates the proliferation of granule cell precursors in the dentate gyrus of the adult rat, we performed both excitotoxic and mechanical lesions of the granule cell layer and examined the numbers of proliferating cells at different survival times. Using [3H]thymidine autoradiography, bromodeoxyuridine labelling and proliferating cell nuclear antigen immunohistochemistry, we observed an increase in proliferating cells on the lesioned side compared to the unlesioned side 24 h after surgery. A significant positive correlation between the extent of granule cell damage and the number of proliferating cells was observed. Combined [3H]thymidine autoradiography and immunohistochemistry for cell-specific markers revealed that the vast majority of proliferating cells had the morphological characteristics of granule cell precursors and were not immunoreactive for vimentin, a marker of immature glia. Combined [3H]thymidine autoradiography and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling for degenerating cells showed that the proliferating cells did not rapidly degenerate. Three weeks after the lesion, most cells produced in response to the lesion had the morphological characteristics of mature granule neurons, were located in the granule cell layer and expressed markers of mature granule neurons, including neuron-specific enolase, the N-methyl-D-aspartate receptor subunit NRI and calbindin. These findings suggest that granule cell death stimulates the proliferation of precursor cells, many of which survive and differentiate into mature granule neurons.

Animals↗

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↗

The epidemiology of louping-ill, a tick borne infection of red grouse (Lagopus lagopus scoticus).

The epidemiology of louping-ill in red grouse was studied in northern Britain concentrating on the possible role of other species and mechanisms of disease persistence. This tick borne viral disease caused heavy mortality in red grouse, particularly chicks. Louping-ill induced mortality reduced the strength of the density dependence that generates the tendency of grouse populations to cycle and in some populations may cause population sinks. Four routes of transmission were examined and non-viraemic transmission of virus between ticks cofeeding on hares was considered significant. Field data supported the hypothesis that disease dynamics is influenced greatly by mountain hares, both as passive amplifiers and as hosts for the tick vector. Genetic variation in louping-ill within Britain was small.

Animals↗

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↗

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↗

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↗

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↗