Biomedical subjects

R B Gibbs

Publications and source records attributed to R B Gibbs.

9 recordsLinked to original sources

PubMed1992

Effects of estrogen and fimbria/fornix transection on p75NGFR and ChAT expression in the medial septum and diagonal band of Broca.

NGF receptor-expressing cells located in the basal forebrain have recently been shown to contain estrogen (E) receptors (Toran-Allerand and MacLusky. 1989. Soc. Neurosci. Abstr. 15: 954). In the present study, we have examined the effects of E-treatment on p75NGFR and choline acetyltransferase (ChAT) expression by neurons in the medial septum (MS) and the vertical (VDB) and horizontal (HDB) limbs of the diagonal band of Broca using immunocytochemical and in situ hybridization techniques. First, since E-treatment has been shown to affect neuronal survival and to stimulate synaptic reorganization and growth within various regions of the brain, we hypothesized that E-treatment might attenuate the loss of p75NGFR immunoreactivity (IR) which occurs in the MS and VDB following transection of the fimbria/fornix. Contrary to our hypothesis, E-treatment did not attenuate the effects of fimbria/fornix transection. In fact, E-treatment alone produced a significant decrease in the number of p75NGFR-IR cells detected in the MS. Subsequent experiments confirmed that chronic E-treatment produces a down-regulation of both p75NGFR-IR and p75NGFR mRNA in the MS and VDB. In the MS, estrogen appeared to affect a subpopulation of p75NGFR-expressing neurons which were also affected by fimbria/fornix transection since the effects of these two treatments were not additive. In addition, effects of E-treatment on p75NGFR-IR were sex-specific (observed in females but not in males) and were reversible in the MS after 2 weeks, but not after 4 weeks (allowing 2 weeks recovery), of E-treatment. A time-course analysis revealed that effects of E-treatment on p75NGFR-IR were not observed until after 16 days (MS) or 30 days (VDB) of E-treatment and were preceded by a significant and transient increase in ChAT expression in both the MS and VDB. The data are consistent with the possibility that continuous, long-term exposure to gonadal steroids may contribute to a loss of p75NGFR-expressing neurons with age. In addition, the data suggest that p75NGFR expression may play a role in regulating the functioning of specific basal forebrain cholinergic neurons. Different mechanisms by which E-treatment might influence ChAT and p75NGFR expression in brain are discussed.

Animals↗

PubMed1992

Role of local environmental factors in determining tissue-specific effects of estrogen: examination of uterine tissues transplanted to brain.

Estrogen stimulates uterine epithelial cells to divide, but not estrogen-concentrating neurons in the adult brain. This effect correlates with recent evidence that estrogen can induce the expression of certain growth-related genes in uterus which are not directly induced by estrogen in the adult brain. The possibility that local diffusible factors play a major role in determining tissue-specific effects of estrogen was examined by transplanting uterine tissues into the brain, muscle and kidney of adult rats and then comparing the effects of estrogen on the incorporation of [3H]thymidine and the expression of Fos-, cdc2- and Rb-like immunoreactivity (IR) on native and transplanted uterine tissues, as well as in estrogen-concentrating regions of the brain adjacent to the uterine grafts. In native uteri, estrogen treatment stimulated Fos-, cdc2-, and Rb-like IR, as well as [3H]thymidine incorporation, within lumenal and glandular epithelial cells. All of these effects were estrogen responsive--no immunoreactive staining within uterine epithelial cells and no signs of epithelial cell proliferation were observed in the native uteri of non-estrogen-treated animals. When uterine tissues were transplanted to brain, Fos-, cdc2-, and Rb-like IR epithelial cells, as well as many [3H]thymidine-incorporating uterine epithelial cells, were observed in all estrogen-treated animals and in some non-estrogen-treated animals as well. Identical results were obtained when uterine tissues were transplanted to skeletal muscle, but not to kidney (in the kidney, transplanted epithelial cells expressed all four parameters but only in estrogen-treated animals, comparable to the native uterus). In contrast, estrogen did not stimulate cell division and did not induce Fos-, cdc2-, or Rb-like IR within estrogen-concentrating neuronal regions of the ventromedial hypothalamus. In addition, the presence of uterine tissue in the brain did not confer the ability of estrogen to stimulate any of these parameters within nearby, estrogen-concentrating regions. These data suggest that there are factors in brain and muscle which can allow uterine epithelial cells to divide in the absence of estrogen. There was no evidence of a diffusible factor in brain which inhibits uterine epithelial cell division, nor of a diffusible factor in uterus which can confer estrogenic stimulation of growth-related genes and cell division to central nervous system neurons. In addition, the data provide the first evidence for estrogen regulation of cdc2 and Rb expression in normal uterus.

Animals↗

PubMed1991

Effects of daytime and nighttime stress on Fos-like immunoreactivity in the paraventricular nucleus of the hypothalamus, the habenula, and the posterior paraventricular nucleus of the thalamus.

Circadian effects on basal and stress-induced Fos-like immunoreactivity (IR) in the paraventricular nucleus of the hypothalamus (PVN), the habenula (Hab) and the posterior paraventricular nucleus of the thalamus (PVN-Thal) were examined. Stress induced a significant increase in the number of Fos-like IR cells within all 3 brain regions. In the Hab, expression was localized specifically to the medial region of the lateral Hab. No differences between the effects of daytime vs nighttime stress on numbers of Fos-like IR cells in the PVN and PVP-Thal were observed. Significantly fewer Fos-like IR cells were observed, however, in the lateral habenula of nighttime vs daytime non-stressed controls, resulting in a significantly greater percentage increase in Fos-like IR in the lateral habenula following nighttime vs daytime stress.

Animals↗

PubMed1991

Effects of fimbria-fornix and angular bundle transection on expression of the p75NGFR mRNA by cells in the medial septum and diagonal band of Broca: correlations with cell survival, synaptic reorganization and sprouting.

Quantitative in situ hybridization techniques were used to examine the effects of lesions which sever hippocampal cholinergic and cortical afferents on p75NGFR mRNA-expressing cells located in the medial septum (MS) and the vertical (VDB) and horizontal (HDB) limbs of the diagonal band of Broca. Animals received either bilateral transection of the fimbria/fornix, unilateral transection of the angular bundle, or sham surgery. Four days later, animals were sacrificed and sections through the MS, VDB and HDB were processed for detection of the p75NGFR mRNA using in situ hybridization techniques previously described (Mol. Brain Res., 6 (1989) 275-287). Transection of the fimbria/fornix and angular bundle differentially affected p75NGFR-expressing cells in the MS, VDB and HDB within 4 days after injury, in ways which were consistent and correlate with subsequent effects on cell survival, synaptic reorganization and growth. In particular, in the MS and VDB, transection of the fimbria/fornix resulted in a significant decrease in the size of p75NGFR-expressing cells (reductions of 25.9% and 15.1% respectively) which was accompanied by a significant reduction (37.9% and 12.7% fewer grains/cell) in relative levels of p75NGFR mRNA. In contrast, in the HDB, transection of the fimbria/fornix had no significant effect on the average size of p75NGFR-expressing cells; however, a significant increase (49%) in the mean relative level of p75NGFR mRNA was observed which may, in turn, reflect a large increase (as much as 2-3 fold) in the levels of p75NGFR mRNA expressed by a subpopulation of hippocampally projecting cholinergic neurons located in the HDB. Finally, transection of the angular bundle resulted in small, but significant increases (9.4% and 10.9%) in relative levels of p75NGFR mRNA in the MS and VDB, as well as an increase (19.6%) in the number of p75NGFR mRNA-expressing cells in the HDB, on the injured side. No increases in p75NGFR expression in the MS, VDB or HDB contralateral to the lesion were observed; however, a decrease in the size (6.9%) and message content (19.4%) of p75NGFR-expressing cells was detected in the MS contralateral to the lesion. Most importantly, all of these effects are consistent with the subsequent effects of these lesions on the survival of basal forebrain cholinergic cells, and the reorganization and growth of cholinergic afferents to the hippocampal formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholinesterase↗

PubMed1991

Thyroidectomy induces Fos-like immunoreactivity within thyrotropin-releasing hormone-expressing neurons located in the paraventricular nucleus of the adult rat hypothalamus.

Effects of thyroidectomy on Fos-like immunoreactivity (IR) in the rat brain were examined using single and double-label immunocytochemical techniques. In particular, the possibility that Fos might be involved in thyroid hormone regulation of thyrotropin releasing hormone (TRH)-containing neurons located in the parvocellular region of the paraventricular nucleus of the hypothalamus (pPVN) was examined. Adult, male, Sprague-Dawley rats were used and all animals received either surgical removal of the thyroid gland or sham surgery. Two experiments were performed. In the first experiment, animals were killed 1, 3, or 6 days after surgery and numbers of Fos-like IR cells in the parvocellular (pPVN) and magnocellular (mPVN) regions of the PVN, the anterior hypothalamic nucleus (AH), the lateral hypothalamic nucleus (LH), and the pyriform cortex were determined. In the second experiment, animals received an intracerebroventricular injection of colchicine 5 days after surgery. The next day, animals were killed and numbers of Fos-like IR cells double-labeled for either TRH, corticotropin releasing factor (CRF), or methionine-enkephalin (met-Enk) were determined. Six days after thyroidectomy there was a significant increase in the number of Fos-like IR cells detected in the pPVN. No induction in the pPVN was observed 1 and 3 days after thyroidectomy, and no effects attributable specifically to thyroidectomy (as opposed to stress) on Fos expression in the mPVN, AH, LH, or pyriform cortex were observed. In addition, a rapid, stress-related, induction of Fos-like IR was detected in the mPVN, AH, and LH and was easily distinguished from Fos expression induced in the pPVN as a function of thyroidectomy. The time course for the effect of thyroidectomy on Fos expression in the pPVN paralleled increased plasma TSH concentration. A significant correlation between numbers of Fos-like IR cells in the pPVN and plasma TSH concentration following thyroidectomy was also observed, suggesting that plasma levels of TSH correlate directly with the number of activated TRH-containing neurons located in the pPVN. Double staining for Fos and TRH, CRF, or met-Enk revealed that thyroidectomy induced Fos-like IR specifically within TRH-, but not within CRF-, or met-Enk, expressing neurons in the pPVN. Taken together, the data suggest that Fos-like IR is induced within TRH-expressing neurons in the pPVN as a consequence of decreasing levels of circulating thyroid hormone (TH). Whether this reflects a direct effect of decreasing TH on Fos expression is not yet known; however, the data are consistent with the hypothesis that Fos is involved in TH-associated regulation of TRH production and release.

Animals↗

PubMed1990

Long-term survival of neural transplants to senescence in rats.

A critical issue for clinical and research applications of transplant techniques is the long-term survival of transplanted tissue and its effect on the host brain. In this study, entorhinal cortices from donor embryos were transplanted into the lesioned angular bundle of juvenile male Sprague-Dawley rats. Animals were maintained for 2 years and then sacrificed for histological and histochemical examinations. The results indicate that entorhinal transplants survive to old age and that both the host and transplant tissues maintain morphological features consistent with those of short-term neural grafts. An unexpected finding of this experiment was the persistence in the transplanted tissue and adjacent host cortex of a pattern of AChE staining which is typical of early postnatal development.

Acetylcholinesterase↗

PubMed1989

Expression of NGF receptor in the rat forebrain detected with in situ hybridization and immunohistochemistry.

The expression of nerve growth factor (NGF) receptor mRNA and NGF receptor protein was examined in the adult rat basal forebrain using in situ hybridization and immunohistochemical techniques. NGF receptor mRNA and protein were detected within cells in the medial septum, diagonal band of Broca, and nucleus basalis of Meynert. Controls showed that the hybridization signal was not due to nonspecific binding of the probe to heterologous RNAs or other molecules. As expected, the distribution of NGF receptor mRNA-containing cells correlated nicely with the distribution of NGF receptor immunoreactive cells in each of these areas. These data extend previous work which suggests that neurons in these areas express the NGF receptor mRNA and manufacture functional NGF receptors. NGF receptor immunoreactivity was also detected in the arcuate nucleus of the hypothalamus, in the leptomeninges at the base of the brain and overlying the tectum, and within ependymal regions along the lateral walls of the cerebral ventricles. A few weakly stained neurons in the lateral hypothalamus and ventrolateral striatum were also consistently observed. In contrast, NGF receptor mRNA was not detected within any meningial, ependymal, or hypothalamic tissues using in situ hybridization. A cross-linking/immunoprecipitation assay demonstrated normal, membrane-bound NGF receptors within extracts of dorsal superior colliculus, ventromedial hypothalamic, and overlying meningial tissues, proving that the staining observed in these areas was not a non-specific artifact associated with the immunohistochemistry. The lack of hybridization in these areas may reflect levels of NGF receptor mRNA which are too low to be detected by the in situ hybridization methods being used. Alternatively, the staining may represent innervation of these areas by afferents whose cell bodies are located elsewhere, and whose terminals contain the NGF receptor protein.

Animals↗

PubMed1975

Epidermolysis bullosa acquisita with electron microscopical studies.

Epidermolysis bullosa acquisita (EBA), one of the rare, scarring, nonhereditary, mechanobullous diseases, occurred in a 74-year-old woman. Clinical histological, and immunofluorescent findings are comparible with those previously reported in cases of EBA. To our knowledge, this is the first report of electron microscopical studies in EBA. Electron microscopy of "normal-looking" skin with EBA shows a noncellular, amorphous material on the dermal side of the basal lamina. Electron microscopy of slightly traumatized skin with EBA is very similar to that seen in dermolytic bullous dermatosis.

Aged↗

PubMed1975

Multiple minute digitate hyperkeratoses.

A 56-year-old man had multiple minute digitate hyperkeratosis. His clinical and histological findings are compatible with those of the only other case reported in the literature.

Biopsy↗