Biomedical subjects

C S Woolley

Publications and source records attributed to C S Woolley.

33 records · Page 2Linked to original sources

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)

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PubMed1992

Adrenal hormones suppress cell division in the adult rat dentate gyrus.

The rat dentate gyrus is unusual among mammalian brain regions in that it shows cell birth well into adulthood. During development, dentate gyrus cell birth is regulated by adrenal steroids. However, it is presently unknown whether cell division in the adult is also mediated by these same factors. In order to determine whether this is the case, we combined adrenalectomy, with or without corticosterone (CORT) replacement, and 3H-thymidine autoradiography, Nissl staining, and immunohistochemistry for the glial cell markers vimentin and glial fibrillary acidic protein (GFAP) as well as for the neuronal marker neuron-specific enolase. Removal of circulating adrenal steroids resulted in a greater density of both GFAP-immunoreactive and vimentin-immunoreactive cells compared to sham-operated animals; CORT replacement prevented increases in both of these cell types. The increase in the density of vimentin-immunoreactive cells probably resulted from an increase in the birth of these cells, as adrenalectomized rats showed greater numbers of 3H-thymidine-labeled vimentin-positive cells compared to sham rats. In contrast, no changes in the number of 3H-thymidine-labeled GFAP-positive cells were observed with adrenalectomy, indicating that the increase in this cell type probably does not involve cell birth. In addition, the density of 3H-thymidine-labeled cells that were not immunoreactive for either glial cell marker and that showed neuronal characteristics was dramatically increased with adrenalectomy. These results suggest that adrenal hormones normally suppress the birth of both glia and neurons in the adult rat dentate gyrus.

Adrenal Cortex Hormones↗

PubMed1992

Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat.

We have found that the density of synapses in the stratum radiatum of the hippocampal CA1 region in the adult female rat is sensitive to estradiol manipulation and fluctuates naturally as the levels of ovarian steroids vary during the 5 d estrous cycle. In both cases, low levels of estradiol are correlated with lower synapse density, while high estradiol levels are correlated with a higher density of synapses. These synaptic changes occur very rapidly in that within approximately 24 hr between the proestrus and estrus stages of the estrous cycle, we observe a 32% decrease in the density of hippocampal synapses. Synapse density then appears to cycle back to proestrus values over a period of several days. To our knowledge, this is the first demonstration of such short-term steroid-mediated synaptic plasticity occurring naturally in the adult mammalian brain.

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PubMed1991

Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. Effects of glucocorticoids on cell death.

The rat dentate gyrus undergoes a period of naturally occurring cell death during the first postnatal week. In the adult rat, removal of circulating adrenal steroids by adrenalectomy is followed by massive death in the granule cell layer, thus raising the possibility that developmental cell death results from low levels of these hormones. Interestingly, the first two postnatal weeks of life in the rat, termed the stress hyporesponsive period, are characterized by very low levels of adrenal steroids. In order to determine whether low levels of adrenal steroids enable developmental cell death to occur in the dentate gyrus, we examined the density of pyknotic and healthy cells in the dentate gyrus of rat pups which received one of the following treatments: (1) injections of the endogenous rat glucocorticoid corticosterone during the first postnatal week, or (2) adrenalectomy at the time when glucocorticoid levels normally rise. Quantitative analysis of the density of pyknotic cells in the granule cell layers revealed significant decreases with corticosterone treatment by the end of the first postnatal week. In these same brains, treatment with corticosterone resulted in a substantial increase in the density of pyknotic cells in the hilus. Adrenalectomy resulted in a significant increase in the density of pyknotic cells in the granule cell layer as well as in the hilus. Despite the dramatic alterations in the density of pyknotic cells with both increases and decreases in glucocorticoid levels, the density of healthy cells remained the same. These observations suggest that glucocorticoids regulate several processes, possibly including neurogenesis and migration, in addition to cell death.

Adrenal Cortex Hormones↗

PubMed1991

Adrenal steroids regulate postnatal development of the rat dentate gyrus: II. Effects of glucocorticoids and mineralocorticoids on cell birth.

Unlike the majority of mammalian brain regions, the rat dentate gyrus undergoes maximal cell birth and cell death during the same developmental time period. Granule cell birth and death peak at the end of the first postnatal week. We have found that manipulations of glucocorticoid levels during the stress hyporesponsive period profoundly influence the density of pyknotic cells in the dentate gyrus while apparently not affecting the density of healthy cells. This raises the possibility that glucocorticoids are regulating processes in addition to cell death, i.e., cell birth. In order to determine whether increases in circulating glucocorticoids or mineralocorticoids affect the birth of cells in the developing dentate gyrus, 3H-thymidine autoradiography was performed on brains of rat pups treated with either corticosterone or aldosterone during the first postnatal week. Quantitative analysis of 3H-thymidine-labelled cells revealed significant decreases in the density of labelled cells in the granule cell layers with both corticosterone and aldosterone treatment. In these same brains, significant decreases in the density of pyknotic cells were also observed in the granule cell layers. However, no changes in the numbers of 3H-thymidine-labelled pyknotic cells were observed with any treatment. Increases in circulating corticosterone or aldosterone resulted in significant increases in the density of both 3H-thymidine-labelled and pyknotic cells in the hilus. These results suggest that dentate gyrus cell birth and cell death are related and that these processes are regulated by adrenal steroids.

Adrenal Cortex Hormones↗

PubMed1991

Effects of aldosterone or RU28362 treatment on adrenalectomy-induced cell death in the dentate gyrus of the adult rat.

Previous studies have shown that granule cells of the adult dentate gyrus require adrenal steroids for their survival. In order to investigate whether activation of type I or type II adrenal steroid receptors can mediate granule cell survival, we have analyzed the density of pyknotic cells in the granule cell, CA1 and CA3 pyramidal cell layers in Nissl stained hippocampal sections from adult male rats which were either sham operated, adrenalectomized, or adrenalectomized and treated with aldosterone as a specific type I receptor agonist or RU28362 as a specific type II receptor agonist. Aldosterone treatment completely protected the dentate gyrus from adrenalectomy-induced cell death, while treatment with RU28362 resulted in only a partial protection against cell death in this region. These results indicate that type I adrenal steroid receptor activation is sufficient to protect against adrenalectomy-induced cell death.

Adrenalectomy↗

PubMed1991

Naturally occurring cell death in the developing dentate gyrus of the rat.

The rat dentate gyrus is a unique brain structure in that most of its neurons are born postnatally. Cell death is known to be an important phenomenon in brain development and yet it is at present unknown whether the dentate gyrus undergoes a period of naturally occurring cell death. In order to determine whether or not cell death plays a role in the development of the dentate gyrus, we examined the density of degenerating cells and healthy cells in the suprapyramidal and infrapyramidal granule cell blades and the hilus during the postnatal period. Light microscopic examination of Nissl-stained brain tissue revealed substantial numbers of pyknotic cells throughout the dentate gyrus during the first postnatal week. Quantitative analysis of the suprapyramidal blade showed a peak in the density of pyknotic cells at the end of the first postnatal week. This peak in the density of degenerating cells coincided with a significant decrease in the density of healthy cells in this region. No rostrocaudal gradient in cell death was observed for the suprapyramidal blade. However, cell death in the suprapyramidal blade proceeded along superficial to deep as well as lateral to medial gradients. Within the infrapyramidal blade/hilus, cell death occurred at different times depending on the rostrocaudal level of the dentate gyrus. Peak density of pyknotic cells was observed the day after birth in the rostral part of the infrapyramidal blade/hilus while pyknosis did not reach a peak in the middle and temporal thirds of this region until the end of the first postnatal week. Cell death in the infrapyramidal blade proceeded in a superficial to deep and lateral to medial direction. These results indicate that the dentate gyrus undergoes a significant period of naturally occurring cell death during the early postnatal period.

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PubMed1991

The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones.

The hippocampal formation is of considerable interest due to its proposed role in a number of important functions, including learning and memory processes. Manipulations of thyroid, gonadal and adrenal hormones have been shown to influence hippocampal physiology as well as learning and memory. The cellular events which underlie these hormone-induced functional changes are largely unexplored. However, studies suggest that hormonal manipulations during development and in adulthood result in dramatic morphological changes within the hippocampal formation. Because neuronal physiology has been suggested to depend upon neuronal morphology, we have been determining the morphologic sensitivity of hippocampal neurons to thyroid and steroid hormones in an effort to elucidate possible structural mechanisms to account for differences in hippocampal function. In this review, hormone-induced structural changes in the developing and adult hippocampal formation are discussed, with particular emphasis on their functional relevance. Sex differences, as well as the developmental effects of thyroid hormone and glucocorticoids, are described. Moreover, the effects of ovarian steroids, thyroid hormone and glucocorticoids on neuronal morphology in the hippocampal formation of the adult rat are reviewed. These hormone-induced structural changes may account, at least in part, for previously reported hormone-induced changes in hippocampal function.

Adrenal Cortex Hormones↗

PubMed1990

Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons.

We have used Golgi-impregnated tissue to demonstrate that exposure to excess glucocorticoids alters dendritic morphology in a specific population of neurons in the adult rat hippocampus. Daily injection of 10 mg of corticosterone for 21 days resulted in decreased numbers of apical dendritic branch points and decreased total apical dendritic length measured in a 100-microns-thick section in CA3 pyramidal cells compared to sham-injected and non-injected controls. In contrast, no changes were observed in CA3 pyramidal cell basal dendritic morphology. Furthermore, no changes were observed in the dendritic morphology of CA1 pyramidal cells or granule cells of the dentate gyrus. Cross-sectional cell body area of any of the 3 cell types examined in this study was unaffected by corticosterone treatment. Finally, qualitative analysis of Nissl-stained tissue from the same brains revealed increased numbers of darkly staining, apparently shrunken CA3 pyramidal cells in corticosterone treated compared to control brains. The changes in dendritic morphology we have observed may be indicative of neurons in the early stages of degeneration, as prolonged exposure to high levels of corticosterone has been shown by others to result in a loss of CA3 pyramidal cells. Additionally, these results suggest possible structural alterations which may occur under physiological conditions in which corticosterone levels are chronically elevated such as in aged animals.

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PubMed1990

Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus.

In order to determine whether short-term glucocorticoid manipulations influence the morphology and survival of neurons in the adult mammalian hippocampal formation, we performed quantitative analyses of Golgi-impregnated and Nissl-stained tissue from the brains of sham operated male rats, adrenalectomized male rats and adrenalectomized male rats which received corticosterone replacement. Three days after adrenalectomy, massive cell death, as detected by a dramatic increase in number of pyknotic cells, was observed in the granule cell layer of the dentate gyrus. By seven days following adrenalectomy, the numbers of pyknotic cells were even greater. Moreover, significant decreases in cross-sectional cell body area and numbers of dendritic branch points of Golgi-impregnated dentate gyrus granule cells were detected at seven days after adrenalectomy. Replacement of corticosterone to adrenalectomized rats prevented the appearance of large numbers of pyknotic cells as well as the decrease in granule cell cross-sectional cell body area and the numbers of dendritic branch points. In contrast, no obvious signs of degeneration were detected in the pyramidal cell layers of the CA1 and CA3 regions of the hippocampus at either three or seven days following adrenalectomy. In addition, no significant changes in morphological characteristics were observed in CA1 or CA3 pyramidal cells with adrenalectomy. These results show that dentate gyrus granule cells require glucocorticoids for their survival and for the maintenance of normal morphology and suggest that granule cell morphology and/or survival may undergo constant fluctuation in response to diurnal rhythms or stress-induced changes in glucocorticoid levels.

Adrenalectomy↗

PubMed1990

Effect of chronic typical and atypical neuroleptic treatment on proenkephalin mRNA levels in the striatum and nucleus accumbens of the rat.

We measured proenkephalin (PEK) mRNA levels in the anterior and medial aspects of the caudate-putamen (CPU) and in the nucleus accumbens (NAc) of the rat by in situ hybridization histochemistry after chronic treatment for 21 days with typical (haloperidol and prolixin) and atypical (molindone, thioridazine, and clozapine) neuroleptics. Chronic administration with these drugs resulted in PEK mRNA levels that were 60-80% higher than controls in the anterior and medial aspects of the CPU but only 25-30% over controls in the NAc. All three atypical neuroleptics studied increased PEK mRNA in the following order: anterior-CPU, thioridazine greater than clozapine and molindone; medial-CPU, thioridazine and molindone greater than clozapine; and NAc, thioridazine much greater than molindone and clozapine. Chronic treatment with the specific dopamine D2 antagonist sulpiride also caused elevation in PEK mRNA levels in all three brain regions studied whereas the specific serotonin S2 receptor blocker, cinanserin, had no significant effects on PEK mRNA levels. These results are consistent with the hypothesis that elevated levels of the enkephalins in the mesolimbic system may be necessary for antipsychotic activity. They also support the idea that the undesirable motoric signs and symptoms observed after chronic treatment with typical neuroleptics may not be the result of increased levels of enkephalins in the basal ganglia because atypical neuroleptics which are almost totally devoid of these side effects caused similar increases in PEK mRNA in the CPU.

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PubMed1990

Gonadal steroids modify dendritic spine density in ventromedial hypothalamic neurons: a Golgi study in the adult rat.

Neurons in the adult rat ventromedial hypothalamic nucleus (VMN, 4-6 neurons per brain; 3-7 brains per group) were studied under various hormonal conditions using the single-section Golgi impregnation technique. Intact rats of both sexes and ovariectomized females treated with oil, estrogen or estrogen and progesterone were used. Golgi-impregnated neurons in the VMN were analyzed to determine possible differences in cell body size, number of primary dendrites, number of dendritic branch-points and spine density. The only significant differences found were in spine density. In the VMN of ovariectomized rats given oil, there were significantly fewer spines on primary dendrites than in either estrogen-treated, estrogen plus progesterone-treated or intact female rats. There were no differences between intact male and female rats observed in any parameter. In addition, when spine density of VMN neurons was assessed throughout the estrous cycle, it was determined that spine density was significantly lower at diestrus than proestrus.

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PubMed1990

Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons.

We have used Golgi-impregnated tissue to demonstrate that apical dendritic spine density in CA1 hippocampal pyramidal cells undergoes a cyclic fluctuation as estradiol and progesterone levels vary across the estrous cycle in the adult female rat. We observed a 30% decrease in apical dendritic spine density over the 24-hr period between the late proestrus and the late estrus phases of the cycle. Spine density then appears to cycle back to proestrus values over a period of several days. In contrast, no significant changes in dendritic spine density across the estrous cycle occur in CA3 pyramidal cells or dentate gyrus granule cells. These results demonstrate rapid and ongoing dendritic plasticity in a specific population of hippocampal neurons in experimentally unmanipulated animals.

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PubMed1990

Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood.

Gonadal steroids are known to influence hippocampal physiology in adulthood. It is presently unknown whether gonadal steroids influence the morphology of hippocampal neurons in the adult intact rat brain. In order to determine whether female sex hormones influence hippocampal morphology in the intact adult, we performed Golgi impregnation on brains from ovariectomized rats and ovariectomized rats which received estradiol or estradiol and progesterone replacement. Removal of circulating gonadal steroids by ovariectomy of adult female rats resulted in a profound decrease in dendritic spine density in CA1 pyramidal cells of the hippocampus. Estradiol replacement prevented the observed decrease in dendritic spine density; progesterone augmented the effect of estradiol within a short time period (5 hr). Ovariectomy or gonadal steroid replacement did not affect spine density of CA3 pyramidal cells or granule cells of the dentate gyrus. These results demonstrate that gonadal steroids are necessary for the maintenance of normal adult CA1 hippocampal pyramidal cell structure. The short time course required to observe these effects (3 d for the estradiol effect and 5 hr for the progesterone effect) implies that CA1 pyramidal cell dendritic spine density may fluctuate during the normal (4-5 d) rat estrous cycle.

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PubMedDate not supplied

Estradiol and progesterone regulate neuronal structure and synaptic connectivity in adult as well as developing brain.

Until recently, it has been widely believed that the adult brain does not undergo changes in its structure, particularly in relation to the actions of circulating hormones. It has now become clear that estradiol and progesterone have important effects on adult brain structure and function. Single section Golgi silver staining and electron microscopy have been used to analyze numbers of spines on dendrites and to count synapses on dendritic spines. In the adult female rat brain, we find that dendrites of neurons in the ventromedial hypothalamus and CA1 region of the hippocampus sprout increased numbers of spines on dendrites and then lose them during the 4- or 5-day estrous cycle. Increased spine numbers are accompanied by increased numbers of synapses on spines. In the hippocampus, the loss of spines and spine synapses occurs during a 24-h period between the time of maximum sexual receptivity on the day of proestrus and the next day, the day of estrus. This loss is not due solely to the decline in estradiol; however, giving progesterone speeds up the decline, and administering the antiprogestin, Ru486, on proestrus blocks the natural decline of synapse density. The changes of synaptic density in the hypothalamus are responsible, at least in part, for the cyclicity of sexual behavior, whereas the cyclicity of synapses in the hippocampus may subserve functions related to spatial learning and memory. In human subjects, cyclic fluctuations in gonadal hormones are associated with cyclic changes in performance on a variety of cognitive and motor tasks.

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