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Biomedical subjects

Z Gottesfeld

Publications and source records attributed to Z Gottesfeld.

At least 19 recordsLinked to original sources
PubMed1991

Maternal and paternal alcohol use: effects on the immune system of the offspring.

There is no single mechanism which can account for such a complex biological phenomenon as immune regulation, nor is it clear how alcohol teratogenicity exerts its multiple adversive effects, including lasting immune deficits. Much of the research aimed at unravelling effects of pre- or early postnatal alcohol exposure on the organism's defense mechanisms and long-term health risks has been phenomenological. A better understanding of mechanisms which underlie alcohol effects on immune competency will require integrated studies of the neuro-immune-endocrine networks.

Adult↗
PubMed1990

Developmental delays associated with prenatal alcohol exposure are reversed by thyroid hormone treatment.

Exposure to alcohol in utero has been associated with hypothyroidism and a variety of developmental defects characteristic of thyroid dysfunction. The present work examined whether these abnormalities could be reversed in infant rats treated with thyroid hormones. Subjects were offspring of dams which were on the following diet regimen during gestation: (1) free access to liquid diet containing ethanol (alcohol pups); (2) an equal volume of isocaloric liquid diet (pair-fed pups); or (3) ad libitum control diet (control pups). Neonates from each group were foster-nursed by control dams, and received triiodothyronine (T3; 0.1 mg/kg/day; s.c.) or saline treatments on postnatal days 1 to 10. The alcohol neonates displayed reduced serum thyroxine which was restored to normal by postnatal day 14. In addition, these pups showed a delayed appearance of developmental landmarks, including righting reflex, dental eruption, auditory startle response and eye opening. The retarded incisor eruption and eye opening were reversed in alcohol pups by T3 treatments. The present data suggest that at least some of the developmental abnormalities associated with prenatal alcohol exposure are attributable to perinatal hypothyroidism and can be restored by early hormone replacement therapy.

Abnormalities, Drug-Induced↗
PubMed1990

Prenatal alcohol exposure alters the development of sympathetic synaptic components and of nerve growth factor receptor expression selectivity in lymphoid organs.

Exposure to alcohol in utero has been associated with long-term immune deficits. In addition, adult mice exposed to alcohol prenatally display altered noradrenergic synaptic transmission selectively in lymphoid organs. This is consistent with the hypothesis that sympathetic neurons play an important role in immunomodulation. The development and maintenance of sympathetic neurons are critically dependent on nerve growth factor (NGF). Furthermore, NGF has been shown to modulate immune responses and NGF receptor expression has been localized to lymphoid organs. The present work examined the effects of prenatal alcohol exposure on the development and maturation of pre- and postsynaptic sympathetic components, including norepinephrine and beta-adrenoceptors, respectively, as well as the early expression of NGF receptors in lymphoid and other organs of the C57BL/6 mouse. Infant mice that were exposed to alcohol in utero displayed reduced levels of norepinephrine and beta-adrenoceptor density, as well as increased NGF receptor expression in the thymus and spleen, but not the heart. These selective changes may account, in part, for the persistent immune incompetence characteristic of fetal alcohol syndrome.

Animals↗
PubMed1990

Lactational alcohol exposure elicits long-term immune deficits and increased noradrenergic synaptic transmission in lymphoid organs.

Increasing evidence suggests that the sympathetic nervous system plays an important role in immunomodulation. While chronic alcohol consumption has been associated with immune deficits, the effects of exposure to alcohol during early postnatal life on subsequent immunocompetence and activity of sympathetic neurons in lymphoid organs are not known. This study examined the long-term effects of lactational alcohol consumption on cellular immune responses and noradrenergic synaptic transmission in lymphoid and other organs of the young adult C57BL/6 mouse. The data show that exposure to alcohol via the mother's milk was associated with long-term deficits in cellular immunity, including suppression of the local graft vs host and contact hypersensitivity responses. The animals also displayed enhanced noradrenergic synaptic transmission and decreased beta-adrenoceptor density selectively in lymphoid organs. These neuroimmune changes are particularly striking since body weight-gain of the suckling pups was normal and their blood alcohol concentration was considerably lower than that of the alcohol-consuming dam. This suggests an increased sensitivity of the nascent immune and nervous systems during the critical period of early postnatal development.

Animals↗
PubMed1990

Prenatal ethanol exposure alters immune capacity and noradrenergic synaptic transmission in lymphoid organs of the adult mouse.

Clinical and experimental evidence indicates that exposure to alcohol in utero is associated with altered immune capacity. The mechanisms underlying such abnormalities are not clear. However, the suggestion that reciprocal interactions between the immune and the nervous systems are necessary for a competent immune response may be relevant. This work examined the consequences of prenatal ethanol exposure on cellular immune responses and noradrenergic synaptic transmission in lymphoid organs of the adult C57B1/6 mouse. Pregnant mice were fed a liquid diet containing 25% of the calories as ethanol (4.8% w/v) or pair-fed an isocaloric equivalent of this diet throughout gestation, followed by foster-nursing the neonates on normal dams. As young adults, mice exposed to ethanol prenatally displayed immunologic and selective neurochemical changes: (1) depressed ability to produce cellular immune responses, including contact hypersensitivity and a local graft-vs-host response, and (2) altered noradrenergic synaptic transmission, including enhanced norepinephrine turnover, and a reduction in norepinephrine levels and beta-adrenoceptor density in the thymus and spleen, but not the heart. However, both the integrity and compartmentation of noradrenergic nerve fibres in the spleen were intact. It is suggested that altered noradrenergic synaptic transmission selectively in lymphoid organs may contribute to the impaired immune capacity associated with fetal alcohol exposure.

Adrenergic Fibers↗
PubMed1989

Prenatal ethanol exposure impairs lesion-induced plasticity in a dopaminergic synapse after maturity.

This study examined the consequences of alcohol (ethanol) exposure during fetal life on lesion-induced dopaminergic synapse responsiveness (plasticity) in the olfactory tubercle of the adult rat. Normally, in the olfactory tubercle, olfactory bulbectomy elicits alterations in pre- and postsynaptic dopaminergic markers, including, respectively, (1) increased tyrosine hydroxylase activity and immunoreactivity, which is associated with dopaminergic axon sprouting, and (2) increased dopaminergic receptor density and potentiated dopamine activation of adenylate cyclase. We have utilized biochemical and quantitative immunocytochemical methodology to examine these synaptic markers in olfactory bulbectomized or sham-operated adult rats. These animals were offspring of dams which were administered one of the following diets during pregnancy: (1) liquid diet containing 35% ethanol-derived calories ad libitum; (2) liquid diet containing an isocaloric amount of maltose-dextrin instead of ethanol, pair-fed; or (3) unaltered liquid diet ad libitum. The results show that prenatal alcohol exposure leads to suppression of the lesion-elicited dopaminergic synapse responsiveness in the olfactory tubercle. There were no significant differences between offspring born to control and pair-fed animals, indicating that the observed abnormalities were not due to alterations in their nutritional status. In conclusion, the present data are a biochemical and quantitative immunocytochemical demonstration of impaired lesion-induced synaptic responsiveness. This renders a new dimension in support of previous evidence indicating that prenatal alcohol exposure leads to altered neuroanatomical, neuroendocrinological and behavioral responsiveness to various challenges. Such impaired synaptic responsiveness may underlie brain functional abnormalities characteristic of fetal alcohol syndrome.

Animals↗
PubMed1987

Chronic exposure to random restraint stress retards the development of estrogen-induced pituitary prolactinoma in rats.

The effects of stress on carcinogenesis have been equivocal. The present work examined the influence of an unpredictable pattern of chronic restraint stress on estradiol-induced pituitary hyperplasia in male Fischer 344 rats. The animals were grouped as follows: (1) control, (2) stressed, (3) estradiol (31 mg), subcutaneous implant for 40 days and (4) estradiol with stress, 1 h daily, randomly, for 40 days. The pituitaries increased markedly in mass in groups 3 and 4 compared to the first two groups. However, the gland weight in rats exposed to estradiol plus stress was significantly (P less than 0.04) reduced as compared to estradiol per se. Prolactin levels increased due to estradiol treatment and decreased following exposure to stress. Weights of adrenal glands increased as a result of estradiol treatment when compared to those in stressed or untreated animals. This adrenal hypertrophy correlated well with plasma corticosterone levels. The data demonstrate that chronic immobilization stress retarded estradiol-induced pituitary prolactinoma. Modulation of the immune response by stress-related factors may play a role in the inhibition of tumorigenesis.

Animals↗
PubMed1987

Deafferentation elicits a transient decrease in Na+, K+-ATPase activity and ouabain binding in the olfactory tubercle.

This work examines the effects of olfactory bulbectomy on Na+, K+-ATPase activity and ouabain binding in the olfactory tubercle. The activity and number of enzyme sites were reduced significantly in olfactory tubercle, but not in corpus striatum or hippocampus, 14 and 21 days after bulbectomy. Enzyme activity and ouabain binding returned to normal by 42 days after the lesions. The time of the reduction in Na+, K+-ATPase coincides with that observed earlier for dopaminergic sprouting and increased dopamine-sensitive adenylate cyclase activity.

Afferent Pathways↗
PubMed1987

Perinatal, not adult, hypothyroidism suppresses dopaminergic axon sprouting in the deafferented olfactory tubercle of adult rat.

We reported recently that chronic thyroid deficiency in rat, beginning in utero and terminating after maturity, suppresses lesion-induced central catecholaminergic axon sprouting in the adult brain [Gottesfeld et al, 1985]. The present work was undertaken to define the critical period of hypothyroidism on subsequent neuronal sprouting. Thyroid hormones deficiency was induced in rats by methimazole during (a) gestational days 8-21 (20 mg/kg/day in the drinking water); (b) postnatal days 1-15 (0.2 or 0.4 mg/pup/day; i.p.), or (c) in the mature animal for 4 weeks (20 mg/kg/day in the drinking water). The olfactory tubercles (OTs) were used as a model to study sprouting of dopaminergic (DA) nerve terminals, elicited by olfactory bulbectomy. Animals in each group received lesions or sham operations as adults, and sacrificed 3 weeks after the operation. Thus, for each of the above treatments four subgroups were formed: (a) euthyroid/sham-operation, (b) euthyroid/lesion, (c) hypothyroid/sham-operation, and (d) hypothyroid/lesion. Sprouting of DA axon terminals in the OTs was identified by biochemical assays and quantitative immunofluorescent microscopy, using tyrosine hydroxylase (TH) as a marker. Serum thyroxine levels served as an index of the thyroid status. The results demonstrate that lesion-induced sprouting of DA axon terminals in OTs of adult rats is suppressed by hypothyroidism induced prenatally or during the early postnatal period, but not after maturity. Thus, there is a perinatal critical period during which altered thyroid function exerts long-term effects on neuronal plasticity.

Animals↗
PubMed1986

Restraint stress during late pregnancy in rats elicits early hypermyelination in the offspring.

Female rats were subjected to a regular, daily schedule of 2 hr of restraint stress during the final 6 days of pregnancy. During the first 2 postnatal weeks, adrenal weights were greater than normal in the offspring of the stressed dams. The concentration of brain myelin was higher than control at 14 and 21 days of age but similar to normal by day 40. Early hypermyelination may be partly responsible for early motor development, as previously observed in prenatally stressed rats.

Aging↗
PubMed1986

Deafferentation elicits increased dopamine-sensitive adenylate cyclase and receptor binding in the olfactory tubercle.

Removal of a major non-catecholaminergic output from the olfactory bulb elicits sprouting of dopaminergic axons in the olfactory tubercle. The functional consequences of this increased dopaminergic innervation are presently not known. This study examined the question of whether lesion-induced sprouting of dopaminergic axons is associated with changes in dopamine-sensitive adenylate cyclase and dopamine receptor density in the partially denervated olfactory tubercle. The results indicate that dopamine- and NaF-stimulated adenylate cyclase activity increased as early as 7 d, while forskolin-sensitive activity increased at 3 d and persisted up to 20 d after lesioning; higher levels of GTP- and NaF-stimulated enzyme activity were found in detergent extracts of olfactory tubercle membranes from 20 d lesioned rats; higher levels of 3H-forskolin binding were found in membranes from 14 and 20 d lesioned rats; and there was an increase in dopamine receptor density, but not affinity, in olfactory tubercle membranes from lesioned rats. The data indicate that lesion-induced dopaminergic sprouting in the olfactory tubercle is temporally coordinated with the increased formation of dopamine receptors, both D1 and D2, the stimulatory guanine nucleotide regulatory protein (Ns) and the catalytic subunit (C) of adenylate cyclase in the postsynaptic membrane.

Adenylyl Cyclases↗
PubMed1985

Prenatal and postnatal hypothyroidism abolishes lesion-induced noradrenergic sprouting in the adult rat.

The effects of altered thyroid states on regeneration in the central nervous system are equivocal. This work was undertaken to examine the influence of propylthiouracil-induced (PTU-induced) pre- and postnatal hypothyroidism on collateral sprouting of noradrenergic (NA) axons in the habenula (Hb), following lesions in the stria medullaris (SM) of the adult rat. Ten pregnant dams were divided into control and PTU-treated groups. Control rats had free access to food and water and the hypothyroid group received, in addition, 0.05% (w/v) of PTU in their drinking water, beginning on day 12 of gestation and continuing post partum through lactation until the offspring were weaned at age 22 days. The pregnant dams received, in addition, daily injections of thyroxine (25 micrograms/kg, ip) and only male pups were used in the study. At weaning the pups were removed from the dams and placed in cages with free access to food and water. The hypothyroid offspring received 0.05% (w/v) PTU in the drinking water until sacrificed at 10 weeks of age. At 6 weeks, some rats in each group received bilateral lesions in the SM and the remainder were sham-operated. All rats were sacrificed 4 weeks after operation. Thus, four groups were formed: 1) control/sham, 2) control/lesion, 3) PTU/sham, 4) PTU/lesion. Sprouting of NA fibers in discrete regions of the Hb was identified by norepinephrine (NE) levels and by fluorescence histochemistry. Blood levels of thyroid stimulating hormone (TSH) were determined. The results show that pre- and postnatal induced chronic hypothyroidism abolished NA sprouting in the partially deafferented Hb. Furthermore, lesions of the SM resulted in a marked decrease in serum TSH levels.

Adrenergic Fibers↗
PubMed1979

Kainic acid-induced neurotoxicity in the striatum: a histofluorescent study.

Histochemical observation of catecholamine terminals in the striatum following kainic acid injections revealed a 'sphere of influence' which contained an increased intensity of dopamine fluorescence as well as non-specific tissue destruction at the injection site. The area of involvement was approximately 50% of the striatum and varied somewhat at any one dose range depending upon the site of injection. It is suggested that destruction of regulatory neuronal systems (cholinergic, GABAergic, peptidergic, etc.) results in a net increase of dopamine in the sphere of kainic acid influence.

Animals↗