摘要:

AbstractAcute maternal ethanol administration to C57B1/6J mice on gestational day 7 (GD7) results in facial and brain abnormalities similar to those reported in human fetal alcohol syndrome (FAS). Using this model, we assessed the damage to brain structures using histological methods and changes in developing neurotransmitter systems with immunocytochemistry. Cholinergic neurons in the forebrain were stained with a monoclonal antibody to choline acetyltransferase (ChAT). Catecholaminergic neurons in the midbrain and serotoninergic neurons in the hindbrain were stained with polyclonal antisera to tyrosine hydroxylase (TH) and serotonin (5‐HT), respectively. Forebrain deficiencies, including loss of midline structures (olfactory bulbs, midline septation, medial septal area) and deficits in lateral and dorsal regions (neostriatum and cerebral cortex) were found in both GD14 embryos and GD18 fetuses. In severely affected offspring, complete loss of the septal region resulted in conjoined lateral ventricles and a reduction in the thickness of the ventricular zone surrounding the single ventricle, as well as a severe loss of ChAT neurons which would normally be located in this territory. However, no consistent changes were seen in the distribution or size of TH or 5‐HT neuronal cell groups in the midbrain and hindbrain. These differences in effects on specific neurotransmitter systems reflect the fact that the forebrain is most severely affected by early ethanol administration, whereas the hindbrain is relatively spared. Such differential effects could produce an imbalance in developing neurotransmitter systems in the embryonic and fetal brain, which could explain some of the functional deficits observed in children with FAS.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90043-2

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe development of mesencephalic catecholaminergic neurons in the embryonic and fetal mouse was analysed in tissues fixed with 5% acrolein using polyclonal rabbit antibodies against tyrosine hydroxylase (TH), the first enzyme in catecholamine synthesis. The first TH positive cells were identified as early as day 8.5–9 of gestation and some expressed TH while apparently still migrating from the proliferative layer. The number of catecholamine cells increased dramatically by embryonic day 9.5–10; at gestation days 10.5–11 numerous TH positive cells bearing many neurites were localized in the ventral part of the mesencephalon but they were not yet separated into two different groups (A9 and A10). After 13 days of gestation two separate catecholaminergic groups could be visualized, although many TH positive cells with long neurites (putative dopaminergic neurons) could still be seen at the edges of the ventricle, and appeared to be moving towards the ventral mesencephalon.On the basis of these results the possibility that catecholamine cells that are produced early during the development of the midbrain may have neurotrophic and/or morphogenetic roles is discussed.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90044-3

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe developmental profiles for binding of α‐[125I]bungarotoxin andl‐[3H]nicotine to putative nicotinic cholinergic receptors were determined in seven mouse brain regions. The overall pattern of development of α‐bungarotoxin binding was similar in all of the regions. Neonatal binding values tended to be greater than those observed in adult brain regions. Maximal binding occurred within 10 days of birth and adult binding values were reached by 20 days of age. The patterns of development of nicotine binding in each of the seven brain regions differed according to region. Gross similarities in developmental profiles for nicotine binding were found among the more caudal and among the more rostral regions. In hindbrain and cerebellum, maximal nicotine binding was found at birth (5 days of age in cerebellum); binding declined approximately 4‐fold by 20 days and remained relatively constant thereafter. In midbrain and hypothalamus, a less extensive decrease in nicotine binding occurred from birth to adulthood (midbrain, 25%; hypothalamus, 50%). Nicotine binding in hippocampus and cortex remained unchanged between birth and adulthood. The developmental pattern for nicotine binding in striatum differed from that found in the other brain regions. At 5 days of age, binding was about 65% of adult binding, which was reached at 30 days of age. In most of the brain regions the developmental profile for α‐bungarotoxin binding was different from that of nicotine. This difference was especially notable in striatum, where adult nicotine binding was higher than neonatal nicotine binding, whereas adult α‐bungarotoxin binding was lower than neonatal α‐bungarotoxin binding.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90045-4

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe effects of congenital hypothyroidism in the late gestation ovine fetus include changes in serotonin concentrations in specific brain areas. To investigate possible ontogenic patterns of changes in 5‐HT receptor function, we studied the binding characteristics of [3H]5‐HT in the midbrain, hypothalamus and cerebral cortex in the late gestation ovine fetus and young lamb. We compared the binding characteristics of control fetuses to those of thyroidectomized fetuses, with or without thyroxine replacement therapy.In each of the areas examined, age‐dependent changes in the receptor density (Bmax) for [3H]5‐HT was observed. In cerebral cortex, Bmaxwas constant from 120 days gestation through the early neonatal period and increased significantly only at 25–30 days after birth. In hypothalamus, [3H]5‐HT binding density decreased late in gestation (140–145 days) with a return after birth to values comparable to those at 120–125 and 130–135 days gestation. The midbrain also exhibited a significant age‐dependent pattern of altered receptor density with a decrease in the 130–135 and 140–145 day gestational age groups compared to both younger and older lambs. In contrast, the affinity constant (Kd) for [3H]5‐HT did not change over the ages evaluated in cerebral cortex or hypothalamus. In the midbrain. however, there was a significant increase in Kdat 1–5 days after birth compared to all other age groups. The ability of fetal thyroidectomy, with or without thyroxine replacement therapy, to alter patterns of [3H]5‐HT binding was also tested. In the hypothyroid animals, examined at 130–135 days gestation, both the cerebral cortex and midbrain receptor affinities (Kd) were the same as control animals and animals of the same gestational age which had undergone throidectomy followed 10 days later by thyroxine treatment. In contrast, the receptor density (Bmax) for [3H]5‐HT was increased significantly in the midbrain of both thyroidectomy animals and animals which had thyroidectomy plus thyroxine treatment.These data demonstrate marked patterns of ontogenic change in characteristics of [3H]5‐HT binding, particularly in the midbrain region of this species. In addition, these studies support the hypothesis that changes in 5‐HT receptor binding which result from hypothyroidism may be an index of thyroiddependent brain maturation.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90046-5

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractIn order to study the effects of a neonatal dopamine lesion on dopaminergic, serotonergic and peptidergic systems, Sprague‐Dawley rats were treated by intracerebroventricular administration of 6‐hydroxydopamine (100 μg, days 3 and 6) following desipramine pretreatment (25 mg/kg s.c.).At 60–70 days postnatally a profound reduction of dopamine‐ and 3,4‐dihydroxyphenylacetic acid levels was found in striatal and limbic forebrain regions concomitant with an extensive loss of tyrosine hydroxylase‐immunoreactive fibers, while no significant alteration in noradrenaline levels was seen. A marked loss of tyrosine hydroxylase‐immunoreactive cell profiles was also observed in the substantia nigra and ventral tegmental area in mesencephalon. In striatum, but not in other regions analysed, an almost 100% increase in serotonin levels and serotonin‐immunoreactive fiber density was observed following 6‐hydroxydopamine treatment. However, the number of serotonin‐immunoreactive cell profiles in the median and dorsal raphe nuclei was not altered. The 6‐hydroxydopamine treatment also led to reductions in substance P levels in striatum, nucleus accumbens and ventral mesencephalon. The cholecystokinin level in nucleus accumbens and neurotensin level in ventral mesencephalon were also reduced. A neonatal intracerebroventricular 6‐hydroxydopamine treatment thus leads to a les̀ion of dopamine neurons in the mesencephalon with extensive loss of dopamine fibers in several forebrain areas, while localized serotonin fiber sprouting is induced in striatum. Furthermore, concomitant reductions of the levels of peptides related to the dopamine system occur following the 6‐hydroxydopamine treatment. Behavioral disturbances such as hyperactivity and cognitive deficiencies occurring after a dopamine lesion early in life might therefore be due to plastic alterations in several different transmitter/ neuromodulator systems as a direct or indirect consequence of the lesion.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90047-6

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractCholine acetyltransferase (ChAT) was measured in the habenula and in the interpeduncular nucleus of rats from 1 to 12 weeks of age. A remarkable degree of parallelism was shown by the developmental curves in the two nuclei. In both cases the highest level of enzyme activity was reached at 3 weeks of age and was followed by some decrease towards adult values. A statistically highly significant correlation was demonstrated between ChAT levels in the two nuclei at the various developmental stages. The rise of the cholinergic marker was slightly advanced in the habenula in comparison with the interpeduncular nucleus. The present data may be useful for studies focused on neonatal synaptogenesis, plasticity and synaptic neurochemistry of this relatively simple model of brain connections.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90048-7

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractNicotine, administered to pregnant Sprague‐Dawley rats either throughout gestation or during two selective prenatal periods before or after muscular innervation (i.e. before or after gestational day 13), accelerated the maturation of developing nerve and muscle as viewed in 2‐week‐old offspring. Prenatal treatment of rats with nicotine (tartrate salt; 0.25 mg/kg twice a day; i.p.) induced marked changes in the contractile force and speed of the developing extensor digitorum longus (EDL) muscle when testedin situon 14 to 15‐day‐old pups. In all nicotine treatment groups isometric twitch and tetanus half contraction durations were shorter than controls. Use of 2,3,5‐triphenyltetrazolium chloride, a biochemical indicator for cellular respiration, showed that totigestational nicotine administration increases cellular metabolic activity of EDL muscle. Hypertrophy of adrenal glands in these animals also was noted. While each of the three courses of nicotine administration accelerated muscle development and maturation, nicotine during the first half of prenatal development, prior to EDL muscle innervation, produced a more dramatic effect than nicotine during the second half of prenatal life.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90049-8

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractLong‐term primary cultures derived from fetal mouse or rat choroid plexus were obtained in serum‐supplemented media. Monoclonal and polyclonal antibodies to basolateral and apical membrane components were used to observe the expression of specific markers of polarity and function. Choroid plexus cultures and thin frozen sections of adult tissues were compared by immunocytochemistry. Two polyclonal antibodies directed against laminin and fibronectin were used on cultured choroid plexus and sectioned tissues, showing that fibronectin and laminin are located on the basolateral membrane domain in ependymocytesin vitro, as well asin vivo. Na+‐K+ATPase was apically detected by light and electron microscopy with a monoclonal antibody (Mab H30) in both cultured cells and sectioned tissues. Double immunofluorescent staining with Mab H30 and affinity‐purified polyclonal antibodies to the α subunit of G0protein (G0α) demonstrated the relatively similar distribution of the two antigens on the apical face of the choroidal tissue, bothin vivoandin vitro. The distribution of these markers shows a typical differentiation with maintenance of polarized features in choroidal ependymocytes in culture, testifying that this cell culture system constitutes an interesting model for studying the functional characteristics of ependymal cells of the choroid plexus.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90050-C

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe results presented here demonstrate non‐specific cholinesterase (nChE) activity in the developing peripheral nerves of chick embryos at stages 25–26 according to Hamburger and Hamilton (1951,J. Morphol.88, 49–92). Under the light microscope the use of simultaneous staining for nChE activity and silver proteinate impregnation revealed the axons to be surrounded by cells exhibiting nChE activity in the main nerve trunks and in the growing tips of nerves. Nerve branches arising from the main nerve trunks contained cells with positive reaction for nChE activity, too. Electron‐dense particles of the reaction product indicating nChE activity were found in the rough endoplasmic reticulum and in the perinuclear envelope of cells in close contact with growing nerve fibers and their growth cones. The same distribution of nChE activity was found in cells which were located near to nerve fasciculi but without direct contact with axons. Surprisingly, the cells in close contact with axons and their growth cones exhibited the end product of nChE activity in the outer part of their plasma membrane. The cells enveloping axons within the nerve trunks were apparently Schwann cells, while those around the growth cones at nerve tips could be identified as Schwann cells and/or mesenchymal cells of the hindlimb. The nChE reaction product was also detected in the axolemma of nerve fibers and their growth cones. The distribution of nChE activity in the developing peripheral nerves of chick embryos suggests that these molecules may influence the process of axonal elongation and locomotion. Several possible mechanisms of nChE action on growing axons can be presumed: (i) intracellular Ca2+level regulation; (ii) providing an adhesive substrate; (iii) butyrate production affecting the cell metabolism and the distribution of neurotubules and neurofilaments. It is also assumed that nChE molecules are involved in the interactions of nerve fibers with Schwann cells and/or mesenchymal cells as well as in interneuronal interactions.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90051-3

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractUsing the immunofluorescence technique, three populations of fibers staining for calcitonin gene‐related peptide are identified in postnatal developing cochleas and in adult rat cochleas. During the maturation of the cochlea, the immunostaining first appears in the basal turn and then extends toward the apex of the cochlea. The first population of immunostained fibers belongs to the lateral olivocochlear innervation. It is observed at postnatal day 4 within the inner spiral bundle of the organ of Corti. The second population of calcitonin gene‐related peptide‐like immunostained fibers belongs to the medial olivocochlear innervation. It is first identified at postnatal day 6 under the outer hair cells, generally in the first row. In the older stages, this population of fibers progressively extends toward the external row of outer hair cells. Finally, the third population of immunostained fibers belongs to the sympathetic supply of the cochlea. They can be identified at postnatal day 6 around the cochlear artery and its branches, and also within the entire modiolus.Our results confirm the presence of calcitonin gene‐related peptide in fibers of the lateral and medial efferent innervations of the cochlea. They indicate an early appearance of calcitonin gene‐related peptide in the developing cochlea, before the onset of the cochlear function, suggesting for this peptide either a neurotrophic function or a regulation of the early cochlear potentials at the level of the lateral efferent synapses.

ISSN:0736-5748    

DOI:10.1016/0736-5748(90)90052-4

出版商:Wiley    

年代:2003

数据来源: WILEY