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PubMed1981

Ascending projections of the brain stem reticular formation in a nonmammalian vertebrate (the lizard Varanus exanthematicus), with notes on the afferent connections of the forebrain.

In the present study an attempt has been made to analyze the ascending reticular projections in the lizard Varanus exanthematicus by means of the horseradish peroxidase (HRP) technique. Reticular projections ascending to the telencephalon were found to arise in the mesencephalon, but not caudal to the mesorhombencephalic border. HRP injections into the dorsal thalamus have demonstrated retrogradely labeled cells in the mesencephalic reticular formation, particularly at the level of the oculomotor nerve and in the medial magnocellular zone of the rhombencephalic reticular formation, predominantly rostrally. HRP infiltrations at the mesodiencephalic border damaged most of the fibers passing beyond this junction, resulting in the uptake of HRP by the damaged axons and subsequent labeling of the cell bodies or origin of ascending reticular projections to the diencephalon and telencephalon. From a comparison of cell-labeling patterns in cases of HRP injections of, respectively, the dorsal thalamus and the mesodiencephalic border, it seems likely that the nucleus reticularis medius and more sparsely the nucleus reticularis inferior project to ventral diencephalic structures (ventral thalamus and hypothalamus), whereas the midbrain reticular formation and the rostral parts of the rhombencephalic reticular formation (nuclei reticulares isthmi and superior) project to both the dorsal thalamus and more ventral diencephalic structures. Projections arising throughout the rhombencephalic reticular formation, but predominantly in the nucleus reticularis inferior, were found to ascend to the midbrain reticular formation. The present experimental data in the lizard Varanus exanthematicus are comparable to the findings in mammals, with the exception of the reticulo-oculomotor pathways which have not been analyzed so far in reptiles. In addition to the aforementioned ascending reticular projections, the present study has demonstrated projections ascending from monoamine cell groups, various diencephalic structures, as well as from neuronal groups involved in somatosensory, auditory, and gustatory systems. Projections were found from the locus coeruleus and the nucleus raphes superior to the telencephalon, as well as from the substantia nigra and the presumable reptilian homologue of the mammalian ventral tegmental area to the basal forebrain and the dorsal thalamus. Bilateral projections were demonstrated from the principal trigeminal nucleus to the telencephalon, reminiscent of the quintofrontal tract of birds. Ascending projections to the diencephalon were found to originate bilaterally in the descending trigeminal nucleus and the dorsal funicular nucleus. Auditory projections to the midbrain arise bilaterally in the superior olivary complex and in the cochlear nuclear complex. Finally, the ascending gustatory pathway arising in the nucleus of the solitary tract was found to project to the "parabrachial region," which in its turn has extensive projections to the forebrain.

Afferent Pathways↗
PubMed1985

Projection systems and terminal localization of dorsal column afferents: an autoradiographic and horseradish peroxidase study in the rat.

Projection systems from the gracile nucleus and the cuneate nuclear complex to their terminal sites in the mesencephalon, diencephalon, and cerebellum were examined by means of anterograde autoradiography and retrograde horseradish peroxidase methods. Three projection systems emerge from the dorsal column nuclei, decussate via internal arcuate fibers, and form the contralateral medial lemniscus (ML). At the obex, some fibers split off the ML and course dorsolaterally, forming an ascending lateral system which fits the "lemniscal adjunct channel" (LAC) concept of Graybiel ('72). The ML continues rostrally as the "main lemniscal line channel" (MLLC). At the inferior colliculus, some LAC fibers terminate in the pontine nuclei, parabrachial, dorsal reticular nuclei, and the external and ventral medial part of the central nucleus of the inferior colliculus. More rostrally at the level of the superior colliculus, terminal fields are found in the medial nucleus of the medial geniculate body, the suprageniculate, pretectal, and mesencephalic reticular nuclei, marking the end of the LAC. In the diencephalon, gracile fibers leave the MLLC and form a crescentlike terminal field along the extreme lateral border of the ventral posterior lateral nucleus (VPL) of the thalamus. Cuneate MLLC fibers terminate in a bandlike formation in the VPL medial to the gracile termination. The third fiber system, the cuneocerebellar projection, emerges from the cuneate, the external cuneate nuclei, and the "cellular bridge" and immediately enters the ipsilateral inferior cerebellar peduncle. Upon entering the cerebellum, the major fiber component remains ipsilateral and terminates as vertical bands in vermal and paravermal lobules, and lobules I through IVa. The posterior cerebellar lobe contains terminal bands in lobules VII-IX, the copula pyramidis, and the paramedian lobule. It is concluded that the dorsolateral fiber system conforms to Graybiel's LAC. It is more divergent and probably less modality specific, whereas the medial lemniscal system conforms to the MLLC, which is said to be modality specific, less divergent, and locked to specific sensory-motor response characteristics. The topography of cerebellar terminal bands indicates that there is sensory-motor representation from all parts of the body to all parts of the cerebellum, at least in the rat.

Afferent Pathways↗
PubMed1986

The distribution of dopamine immunoreactivity in the forebrain and midbrain of the lizard Gekko gecko: an immunohistochemical study with antibodies against dopamine.

The distribution of dopamine (DA) immunoreactivity in the forebrain and the midbrain of the lizard Gekko gecko was studied by using recently developed antibodies against DA. Dopamine-containing cells were found around the glomeruli of the olfactory bulb, in several parts of the periventricular hypothalamic nucleus, in the periventricular organ, the ependymal wall of the infundibular recess, the lateral hypothalamic area and the pretectal posterodorsal nucleus of the diencephalon, and in the ventral tegmental area, the substantia nigra, and the presumed reptilian equivalent of the mammalian A8 cell group of the mesencephalon. Dopaminergic fibers and terminals were observed throughout the whole brain, but particularly in the diencephalon and the telencephalon. The nucleus accumbens appears to have the most dense innervation, but also the striatum, amygdaloid complex, olfactory tubercle, septum, and dorsal ventricular ridge (especially its superficial zone) show numerous DA-containing fibers and terminals. Except for the lateral cortex, cortical areas are not densely innervated by DA fibers. In several respects DA distribution in the gekkonid brain differs from that in other reptiles studied. For instance, in the Gekko the dorsal ventricular ridge is densely innervated by DA fibers, whereas in turtles and crocodiles the same structure shows only weak catecholaminergic histofluorescence. When compared to the distribution of DA immunoreactivity in mammals, it appears that the DA system in the gekkonid telencephalon resembles the distribution of DA in the limbic forebrain and striatum of mammals. Whether these similarities in distribution of DA also imply similarities in function will be discussed.

Animals↗
PubMed1986

Cholinergic neurons of the laterodorsal tegmental nucleus: efferent and afferent connections.

The ascending projections of cholinergic neurons in the laterodorsal tegmental nucleus (TLD) were investigated in the rat by using Phaseolus vulgaris leucoagglutinin (PHA-L) and wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) anterograde tracing techniques. Two ascending pathways were identified after iontophoretic injections of PHA-L into the TLD. A long projection system courses through the dorsomedial tegmentum, caudal diencephalon, medial forebrain bundle, and diagonal band. Different branches of this system innervate the midbrain (superior colliculus, interstitial magnocellular nucleus of the posterior commissure, and anterior pretectal nucleus), the diencephalon (lateral habenular nucleus, parafascicular, anteroventral, anterodorsal, mediodorsal, and intralaminar thalamic nuclei), and the telencephalon (lateral septum and medial prefrontal cortex). The second system is shorter and more diffuse and innervates the median raphe, interpeduncular, and lateral mammillary nuclei. Retrograde tracing with WGA-HRP, combined with choline acetyltransferase immunohistochemistry, revealed that most of the TLD projections to the tectum, pretectum, thalamus, lateral septum, and medial prefrontal cortex are cholinergic. Afferents to the TLD were studied by anterograde and retrograde tracing techniques. Injection of tracers into the TLD retrogradely labelled neurons bilaterally in the midbrain reticular formation, the periaqueductal gray, the medial preoptic nucleus, the anterior hypothalamic nucleus, and the perifornical and lateral hypothalamic areas. Retrogradely labelled cells were also located bilaterally in the premammillary nucleus, paraventricular hypothalamic nucleus, zona incerta, and lateral habenular nucleus. In the telencephalon, the nucleus of the diagonal band and the medial prefrontal cortex contained retrogradely labelled neurons ipsilateral to the TLD injection site. The projections of the medial prefrontal cortex, the bed nucleus of the stria terminalis, and the lateral habenular nucleus to the TLD were confirmed in anterograde tracing studies. These findings indicate that the TLD gives rise to several ascending cholinergic projections that innervate diverse regions of the forebrain. Afferents to the TLD arise in hypothalamic and limbic forebrain regions, some of which appear to have reciprocal connections with the TLD. The latter include the lateral habenular nucleus and medial prefrontal cortex.

Animals↗
PubMed1987

Specific neurotrophic interactions between cortical and subcortical visual structures in developing rat: in vitro studies.

We investigated the influence of different subcortical structures on the survival of specific populations of occipital cortex neurons developing in vitro. Explants of embryonic day 14-15 (E14-15) rat cortex were cultured for 5 days with explants of either diencephalon or optic tectum or another occipital cortex explant. Stereological analysis of the explants revealed that after 5 days in vitro (5 DIV) all the cortical explants contained equal proportions of healthy neurons, glia, neuropil, and degenerating profiles, regardless of the culturing conditions. In order to determine if different neuronal populations survived preferentially in the cortical explants as a result of the presence of potential target or afferent structures, we used HRP filling and 3H-thymidine labeling techniques. Specific differences in the morphology of the cells and their time of origin are found in the cortical explants. In the cortical explants cocultured with diencephalon (Cx + D) the cortical cells that survive tend to be round with small cross-sectional areas and have few neurites. These cells are generated late in the culturing period. The surviving cortical neurons in the cortex plus tectum (Cx + T) cultures are larger--many with a pyramidal-shaped soma and several neurites. These cells are generated earlier in vitro. The cortex cultured with other cortex (Cx + Cx) gives values intermediate to the Cx + D and Cx + T cultures. The results of these experiments suggest that there are diffusible trophic factors that arise from subcortical structures that selectively support the survival of neuron populations in the developing neocortex.

Animals↗
PubMed1987

Localization of immunoreactive tyrosine hydroxylase in the goldfish brain.

This report describes the distribution of tyrosine hydroxylase immunoreactive (TH-ir) structures in the brain of the goldfish (Carassius auratus). The localization of TH-ir cell groups revealed by immunocytochemical techniques is largely in accordance with catecholamine distribution previously reported in teleosts by using monoamine fluorescence; however, in the telencephalon and diencephalon, several new cell groups are elucidated. In the telencephalon, TH-ir cell bodies are observed in the olfactory bulb, area ventralis telencephali, and the central zone of the area dorsalis telencephali. TH-ir fibers and terminals are moderately dense throughout the telencephalon except for a sparse innervation of the area dorsalis, pars medialis. Immunostained cells are present in the suprachiasmatic nucleus and magnocellular and parvicellular components of the preoptic nucleus. Immunoreactive fibers from preoptic cells can be traced caudally in two main tracts to the infundibulum. Dense immunoreactivity around cells in the pituitary provides anatomical support for catecholamine involvement in the neuroendocrine axis probably via preopticohypophysial connections. At middiencephalic levels, immunoreactive cells are present in the ventral thalamus, nucleus pretectalis periventricularis, pars ventralis, and paraventricular organ pars anterioris. In the caudal diencephalon, TH-ir cells are seen within the posterior tuberal nuclei and dorsal to posterior recess. No immunostained cells are observed in the midbrain. In the hindbrain, tyrosine hydroxylase containing cells comprise three groups similar to that described using Falck-Hillarp histofluorescence (Parent et al., '78), i.e., isthmal, central medullary, and medullospinal groups. Tyrosine hydroxylase immunoreactivity is interpreted as evidence for the presence of catecholamines and not only provides an anatomical basis for the functional significance of catecholamines in teleosts, but may be useful in elucidating homologous structures in tetrapod vertebrates, although certain sites of immunoreactivity may prove to be unique to teleosts.

Animals↗
PubMed1988

Mesodiencephalic projections to the vestibular complex in the cat.

The distribution of cells in the rostral medial mesencephalon and caudal diencephalon which project to the vestibular complex was mapped in the cat by using retrograde axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Subsequent experiments using anterograde transport of WGA-HRP clarified the position of the terminations of the mesodiencephalic-derived afferents in the vestibular complex. After large injections which involved the entire vestibular complex, retrogradely labeled cells were seen in both the ipsilateral and contralateral interstitial nucleus of Cajal (INC) and were more numerous in its rostral pole. Labeled cells also occurred in the perifascicular region, both immediately adjacent to the fasciculus retroflexus and rostroventral to it. Fusiform midline cells of the Edinger-Westphal nucleus were also labeled, as well as a number of cells in the adjacent somatic portion of the oculomotor complex (OMC). Another group of labeled cells was observed within the contralateral medial terminal nucleus of the accessory optic tract (MTN) and in the posterior hypothalamic nucleus. Injections limited to subregions of the vestibular complex resulted in similar but slightly varying distributions and numbers of retrogradely labeled cells. After injections covering the caudal half of the medial vestibular nucleus (MVN) and descending vestibular nucleus (DVN), labeled cells in the INC and tegmentum dorsal to it were especially prominent, but none was seen in the MTN or OMC. Injections placed in the rostral MVN, lateral vestibular nucleus, y group, and superior vestibular nucleus resulted in a distribution of labeled cells similar to that seen following global vestibular injections, but these cells were fewer in number. After an injection confined to the y group, a small number of retrogradely labeled cells were seen in the rostral pole of the INC and immediately ventral to the fasciculus retroflexus. Projections from the rostral medial mesencephalon and caudal diencephalon to the MVN, DVN, and y group were confirmed by using anterograde transport of WGA-HRP. Direct projections from the INC-perifascicular regions and somatic neurons of the OMC to the caudal vestibular complex could play a role in eye-head coordination. Those projections from the rostral INC and MTN to the rostral vestibular complex may play a role in vertical eye movements and responses to visual stimuli which move in the vertical plane.

Afferent Pathways↗
PubMed1989

Autoradiographic distribution of thyrotropin-releasing hormone receptors in the African lungfish Protopterus annectens.

We used quantitative autoradiography to examine the distribution of thyrotropin-releasing hormone (TRH) receptors in the central nervous system (CNS) of the African lungfish Protopterus annectens. We found that the distribution of TRH receptors throughout the CNS of the lungfish was heterogeneous with the highest concentrations (500-800 fmol/mg protein) in the olfactory bulb and telencephalon, moderately high concentrations (200-500 fmol/mg protein) in the diencephalon, and moderate (50-200 fmol/mg protein) to low (less than 50 fmol/mg protein) concentrations in the brainstem and spinal cord. Except for the motor nuclei of the cranial nerves and spinal cord, TRH receptors were concentrated in the acellular regions. In the telencephalon and diencephalon, the receptor density was inversely related to cellular density. These results provide a neuroanatomic and neuropharmacologic basis for further investigations of TRH in the African lungfish.

Animals↗
PubMed1990

Sources of subcortical GABAergic projections to the superior colliculus in the cat.

The goal of this study was to identify GABAergic input to the cat superior colliculus from neurons located in the caudal diencephalon, mesencephalon, pons and medulla. Cells efferent to the superior colliculus were labeled retrogradely with the tracer horseradish peroxidase, and an antibody to gamma-aminobutyric acid was used to label GABAergic neurons in the same sections. The results indicate that neurons in several distinct areas of the caudal diencephalon and brainstem are both immunocytochemically labeled for GABA and retrogradely labeled with horseradish peroxidase. These areas include zona incerta, nucleus of the posterior commissure, anterior and posterior pretectal nuclei, nucleus of the optic tract, superior colliculus, cuneiform nucleus, subcuneiform area, substantia nigra pars reticulata and pars lateralis, periparabigeminal area, external nucleus of the inferior colliculus, the area ventral to the external nucleus of the inferior colliculus, mesencephalic reticular formation, dorsal and ventral nuclei of the lateral lemniscus, and the perihypoglossal nucleus. The role that such diverse inhibitory input to the superior colliculus might play, particularly in influencing eye movements, is discussed.

Animals↗
PubMed1991

Distribution of galanin-like immunoreactivity in the brain of Rana esculenta and Xenopus laevis.

The immunocytochemical distribution of galanin-containing perikarya and nerve terminals in the brain of Rana esculenta and Xenopus laevis was determined with antisera directed toward either porcine or rat galanin. The pattern of galanin-like immunoreactivity appeared to be identical with antisera directed toward either target antigen. The distribution of galanin-like immunoreactivity was similar in Rana esculenta and Xenopus laevis except for the absence of a distinct laminar distribution of immunoreactivity in the optic tectum of Xenopus laevis. Galanin-containing perikarya were located in all major subdivisions of the brain except the metencephalon. In the telencephalon, immunoreactive perikarya were detected in the pars medialis of the amygdala and the preoptic area. In the diencephalon, immunoreactive perikarya were detected in the caudal half of the suprachiasmatic nucleus, the nucleus of the periventricular organ, the ventral hypothalamus, and the median eminence. In the mesencephalon, immunoreactive perikarya were detected near the midline of the rostroventral tegmentum, in the torus semicircularis and, occasionally, in lamina A and layer 6 of the optic tectum. In the myelencephalon, labelled perikarya were detected only in the caudal half of the nucleus of the solitary tract. Immunoreactive nerve fibers of varying density were observed in all subdivisions of the brain with the densest accumulations of fibers occurring in the pars lateralis of the amygdala and the preoptic area. Dense accumulations of nerve fibers were also found in the lateral septum, the medial forebrain bundle, the periventricular region of the diencephalon, the ventral hypothalamus, the median eminence, the mesencephalic central gray, the laminar nucleus of the torus semicircularis, several laminae of the optic tectum, the interpeduncular nucleus, the isthmic nucleus, the central gray of the rhombencephalon, and the dorsolateral caudal medulla. The extensive system of galanin-containing perikarya and nerve fibers in the brain of representatives of two families of anurans showed many similarities to the distribution of galanin-containing perikarya and nerve fibers previously described for the mammalian brain.

Animals↗
PubMed1992

Diencephalic projections from the superficial and deep laminae of the medullary dorsal horn in the rat.

An important function of the medullary dorsal horn (MDH) is the relay of nociceptive information from the face and mouth to higher centers of the central nervous system. We studied the central projection pattern of axons arising from the MDH by examining the axonal transport of Phaseolus vulgaris-leucoagglutinin (PHA-L). Labeled axon and axon terminal distributions arising from the MDH were analyzed at the light microscopic level. After large injections of PHA-L into both superficial and deep laminae of the MDH in the rat, labeled axons were observed in the nucleus submedius of the thalamus (SUB), ventroposterior thalamic nucleus medialis (VPM), ventroposterior thalamic nucleus parvicellularis (VPPC), posterior thalamic nuclei (PO), zona incerta (ZI), lateral hypothalamic nucleus (LH), and posterior hypothalamic nucleus (PH). Restriction of PHA-L into only the superficial laminae resulted in heavy axon and varicosity labeling in the SUB, VPM, PO, and VPPC and light labeling in LH. In contrast, after injections into deep laminae, labeled axons were mainly distributed in ZI and PH; some were also in VPM and LH, and fewer still in PO and SUB. Varicosities in VPM, SUB, and PO were significantly larger than those in VPPC, ZI, LH, and PH. Varicosity density was highest in SUB and lowest in the VPPC. We concluded that there are two distinct nociceptive pathways, one originating from the superficial MDH and terminating primarily in the dorsal diencephalon and the second originating from deep laminae of the MDH and terminating primarily in the ventral diencephalon. We propose that in the rat, input from the deeper laminae is primarily involved in the motivational-affective component of pain, whereas input from the superficial MDH is related to both the sensory-discriminative and motivational-affective component of pain.

Animals↗
PubMed1994

Distribution of galanin-like immunoreactivity in the brain of the turtle Mauremys caspica.

Galanin is a brain-gut peptide present in the central nervous system of fish, amphibians, birds, and mammals. For comparative studies among vertebrates, the distribution of galanin in the brain of reptiles has been investigated. We studied the localization of galanin-like-immunoreactive perikarya and nerve fibers in the brain of the turtle Mauremys caspica by using an antiserum against porcine galanin. In the telencephalon, few immunoreactive perikarya were seen in the amygdaloid complex. The diencephalon contained the majority of the immunoreactive perikarya present in the lamina terminalis, nucleus periventricularis anterior, lateral preoptic area, nuclei hypothalamicus ventromedialis and posterior, nucleus basalis of the anterior commissure, and nucleus ventralis tuberis. Many immunoreactive cells, especially in the infundibulum, contacted the cerebrospinal fluid by an apical process. In the rhombencephalon, immunopositive perikarya were restricted to a few cells in the nucleus tractus solitari. In the mesencephalon, they were absent. Immunoreactive nerve fibers were present in all regions containing labeled perikarya and in 1) telencephalon: septum, nucleus fasciculi diagonalis Brocae; 2) diencephalon: nucleus paraventricularis, nucleus supraopticus, nucleus suprachiasmaticus, subventricular grey, nucleus of the paraventricular organ, nucleus mamillaris, infundibular decussation, outer layer of the median eminence, posterior commissure and subcommissural organ region, habenula, nuclei dorsomedialis anterior, and dorsolateralis anterior of the thalamus; and 3) mesencephalon and rhombencephalon: stratum griseum periventriculare, stratum fibrosum periventriculare, laminar nucleus of the torus semicircularis, periventricular grey, nucleus interpeduncularis, nucleus ruber, substantia nigra, locus coeruleus, raphe nuclei, nuclei of the reticular formation, nucleus motorius nervi trigemini, cochlear and vestibular area, and nucleus spinalis nerve trigemini. Our results suggest that galanin may have hypophysiotropic and central roles in the turtle Mauremys caspica.

Animals↗
PubMed2002

Chimeric analysis of Notch2 function: a role for Notch2 in the development of the roof plate of the mouse brain.

Notch proteins are transmembrane receptors involved in cell-fate determination throughout development. Targeted disruption of either the Notch1 or Notch2 gene in mice results in embryonic lethality around embryonic day (E) 10.5 with widespread cell death. Although Notch1-deficient mice show disorganized somitogenesis, Notch2 mutants did not show definitive abnormalities in any tissue expressing high levels of the Notch2 gene, including the central nervous system. To study Notch2 function in development beyond the embryonic lethal stage, we performed chimeric analysis between Notch2 mutant and wild-type mouse embryos. Chimeric embryos developed normally and homozygous Notch2 mutant-specific cell death was not observed. Although chimeric embryos showed normal mosaicism until E9.5 in all tissues studied to date, Notch2 homozygous mutant cells failed to contribute to formation of the roof plate of the diencephalon and mesencephalon at later developmental stages, when Notch2 is normally expressed at high levels at there. Furthermore, Notch2 heterozygous mutant cells were also excluded from the roof plate of the chimera, however, Notch2 heterozygous mutant mice developed normally. We also showed that Wnt-1 and Mash1 expression patterns at the roof plate were disorganized in Notch2 homozygous mutant embryos. These results indicate that Notch2 plays an important role in development of the roof plate of the diencephalon and mesencephalon, and suggest that cellular rearrangement is involved in this process.

Animals↗
PubMed1981

Regional distribution of myelin basic protein in the central nervous system of quaking, jimpy, and normal mice during development and aging.

Myelin basic protein (MBP) was quantified using a RIA technique in the spinal cord, cerebellum, diencephalon plus brainstem region and cerebral hemispheres of two dysmyelinating murine mutants, quaking (qk) and jimpy (jp) mice. Comparison was made with normal control values. The whole life-span has been investigated: ie, ages ranging from 0 to 26 days for the jp, O to one year for the qk, and prenatal stage to three years for the control animals. Assays in the mutants at early ages were rendered feasible by the use of marker genes, which has allowed the diagnosis of the mutation at birth, 12 days before the expression of their typical tremor phenotype. Special care was given to the period of early myelinogenesis in order to clarify the dysynchrony between the various parts of the central nervous system. In normal mice, MBP was already detected in the brain of 19-day-old embryos. During development, rapid accumulation of MBP first occurred in the spinal cord then in the diencephalon, the brainstem, the cerebellum, and finally in the cerebral hemispheres. In the 25-day-old jimpy mutant, levels of MBP were found dramatically decreased, never exceeding 6% of the normal controls in any of the areas investigated. The situation for the quaking mouse was quite different. This mutant could be investigated up to one year old. At that age, a high discrepancy was observed between the values found in the brain and in the spinal cord (respectively, 10% and 35%) compared to normal controls. In both mutants, not only were the levels of MBP decreased, but also its appearance during development was delayed. Nevertheless, in both mutants the caudo-rostral timing of myelination as assayed by MBP levels was maintained. Furthermore, the later myelination occurred, the stronger weas the deficit in MBP. Interestingly, in the quaking mutant, the specific plasticity of the spinal cord was exemplified by its ability to reduce constantly, even at an advanced age, its initial deficit of MBP.

Aging↗
PubMed1988

Activators of protein kinase C enhance cyclic AMP accumulation in cerebral cortical and diencephalic neurons in primary culture.

The effects of the active phorbol ester 12-myristate, 13-acetate (PMA), the inactive ester 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), and the synthetic diacylglycerol 1-oleoyl-2-acetyl-glycerol (OAG) on cyclic AMP production were examined in rat cerebral cortical and diencephalic cells. With the aid of a prelabeling technique for measuring cyclic AMP accumulation in the cells, it was found that neither PMA nor OAG significantly increased cyclic AMP formation in either type of cell. In contrast, PMA enhanced the cyclic AMP response to vasoactive intestinal peptide (VIP) and forskolin in cerebral cortical and diencephalic cells, whereas 4 alpha-PDD was inactive. A 15-min preincubation was used to obtain maximal enhancement. The concentration dependence of PMA on VIP-stimulated cyclic AMP accumulation was determined in cortical cells (EC50 = 6.2 x 10(-8) M). OAG was also able to potentiate VIP-induced cyclic AMP formation in cortical and diencephalic cells. However, its potentiating effect was weaker than that observed with PMA treatment. The data show, at an early stage of development (primary cultures, 8-10 days), a modulation of VIP- or forskolin-cyclic AMP response by the activators of protein kinase C, i.e., PMA and OAG, in two different structures of the central nervous system: the cerebral cortex and the diencephalon. To our knowledge, this is the first demonstration of such a potentiation within the diencephalon.

Animals↗
PubMed1995

Nature and distribution of gonadotropin-releasing hormone (GnRH) in the brain, and GnRH and GnRH binding activity in serum of the spotted dogfish Scyliorhinus canicula.

The distribution of different molecular forms of gonadotropin-releasing hormone (GnRH) in the brain and serum of the spotted dogfish, Scyliorhinus canicula, was investigated by an indirect immunofluorescence method, using antisera against salmon (s-), chicken-II (cII-) and mammalian (m-) GnRHs, and by reverse-phase high-performance liquid chromatography (RP-HPLC) coupled with radioimmunoassays. Five GnRH molecular forms were demonstrated on the basis of the retention time in the RP-HPLC system. The characteristics of four of these GnRH peptides are consistent with those of m-, cII-, dogfish (df-), and sGnRH. The fifth form appears to be novel. Immunoreactive sGnRH structures were confined to the diencephalon; whereas cIIGnRH and mGnRH were found in the telencephalon and diencephalon. cIIGnRH- and dfGnRH-like molecules were detected in the serum. Moreover, a specific, low-affinity GnRH binding protein (GnRH-BP) was found in the serum of the spotted dogfish. The binding of [125I]sGnRHA to the serum GnRH-BP was dependent on incubation time, equilibrium being reached within 1 hr at 4 degrees; binding was rapid and completely reversible. Scatchard analysis yielded a linear plot with a Kd of 7.9 x 10(-7) M. The presence of a GnRH-BP in spotted dogfish serum suggests a probable action of GnRH via the general circulation.

Animals↗
PubMed2000

Gonadotropin-releasing hormones in the brain and pituitary of the teleost, the white sucker.

The present study investigated GnRH forms within the brain of a representative of the order Cypriniformes, the white sucker, Catostomus commersoni, using HPLC, RIA, and immunocytochemistry. Several immunoreactive (ir) GnRH forms were identified in the brain of the white sucker by chromatography and radioimmunoassay, including ir-salmon GnRH, ir-lamprey GnRH-I and -III, and ir-chicken GnRH-II. Results from immunocytochemical studies were consistent with multiple GnRH forms distributed in different patterns, particularly for fibers. Neuronal perikarya containing ir-salmon GnRH and ir-lamprey-like GnRH were found laterally within the preoptic area and rostral hypothalamus. Cells containing exclusively ir-salmon GnRH appeared slightly more rostrally, but in the same region. Fibers containing ir-salmon GnRH and ir-lamprey-like GnRH were seen throughout the caudal telencephalon and extended into the diencephalon, toward the pituitary. Fibers containing ir-chicken-II-like GnRH were also seen in the caudal telencephalon, but were concentrated more dorsally in the diencephalon. Within the pituitary, fibers containing ir-salmon GnRH and ir-lamprey-like GnRH entered the neurohypophysis, but differed in their destinations. Fibers containing ir-salmon GnRH remained within the neurohypophysis, while fibers containing ir-lamprey-like GnRH targeted adenohypophyseal tissue. These findings are consistent with the hypothesis that multiple GnRH forms with multiple functions exist within the brain and pituitary of teleosts and provide further evidence of a lamprey-like GnRH within an early evolved teleost species.

Amino Acid Sequence↗
PubMed1996

The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome.

We have recently isolated a human homolog (hSIM) of the Drosophila single-minded (sim) gene from the Down syndrome critical region of chromosome 21 using the exon trapping method. The Drosophila sim gene encodes a transcription factor that regulates the development of the central nervous system midline cell lineage. To elucidate the structure of the mammalian SIM protein, we have isolated cDNA clones from a mouse embryo cDNA library. The cDNA clones encode a polypeptide of 657 amino acids with a bHLH (basic-helix-loop-helix) domain, characteristic of a large family of transcription factors, and a PAS (Per-Arnt-Sim) domain in the amino-terminal half region. Both of these domains have striking sequence homology with human SIM and Drosophila SIM proteins. In contrast, the carboxy-terminal half of the mouse SIM protein consists of a proline-rich region with no sequence homology to the Drosophila SIM protein. A similar proline-rich domain is known for the activator domain of a number of transcription factors. Whole-mount embryo in situ hybridization experiments revealed that the SIM mRNA is expressed prominently in the diencephalon of mouse embryos at 8-9.5 days postcoitum. The structural characteristics of the mouse SIM protein and its expression in the diencephalon during embryogenesis strongly suggest that the newly isolated mammalian SIM homolog may play a critical role in the development of the mammalian central nervous system. We propose that the human SIM gene may be one of the pathogenic genes of Down syndrome.

Animals↗