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B Tinner

Publications and source records attributed to B Tinner.

At least 37 records · Page 2Linked to original sources

Differential brain area vulnerability to long-term subcortical excitotoxic lesions.

To investigate the long-term effects of excitatory amino acid microinjections into the basal forebrain and its correlation with a possible Ca2+ imbalance associated with the excitotoxic process, ibotenic acid, mainly an N-methyl-D-aspartate receptor agonist, and quisqualic acid, an agonist of non-N-methyl-D-aspartate receptors, were injected into two regions rich in cholinergic neurons, namely the medial septal nucleus and the ventral globus pallidus. Within the globus pallidus but not within the medial septal nucleus, 13 days and one year postlesion, nerve cell death was associated with the appearance of calcium deposits within the large putative GABAergic pallidal neurons, being more pronounced in ibotenic acid than quisqualic acid-lesioned rats. An intermediate two month post-lesion study with alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and ibotenic acid microinjections in globus pallidus demonstrated that the AMPA subtype of glutamate receptor may also be involved in this Ca2+ imbalance, together with the N-methyl-D-aspartate and metabotropic subtype receptors. Quisqualic acid lesions in globus pallidus and medial septum were associated with a substantial disappearance of cholinergic cell bodies and their nerve terminal networks within the cerebral cortex and hippocampal formation respectively, as assessed by choline acetyltransferase and acetylcholine esterase immunocytochemistry. Ibotenic acid lesions resulted in a lower reduction of cholinergic markers. One year after septal lesions induced either by ibotenic or quisqualic acid, a marked atrophy of the entire dorsolateral septal nucleus was observed. Our results support the hypothesis that brief and intense glutamate exposure can induce long-term neurodegenerative processes and give evidence that long-term excitotoxic lesions of the two areas studied result in marked differences in neuronal damage, including intracellular calcium deposits which do not correlate with the cholinergic deficits produced by multiple glutamate receptor subtypes.

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Glial and neuronal glucocorticoid receptor immunoreactive cell populations in developing, adult, and aging brain.

A detailed mapping of glucocorticoid receptor (GR) immunoreactivity (IR) in rat CNS was performed employing a mouse monoclonal antibody against rat liver GR. Subjective comparisons were made between the present results and the available data in the literature. A semiquantitation of GR immunostaining was found necessary and was obtained by microdensitometric and morphometric techniques, which enabled the distinction of neuronal and glial cell populations containing GR IR in various CNS regions. GR IR in the CNS was mainly found in the nuclear compartment. The GR was present in neuronal populations with classical neurotransmitters, especially monoamines and glutamate and with various neuropeptides. The degree of colocalization varied according to the function of the brain area. Functional implications were made in relation to stress sensitivity, mood and nociception/antinociception. The global control of networks by glucocorticoids may allow an optimal integration of different types of circuits. The GR is found already in the fetal rat and the development of GR mRNA and receptor protein was followed during the pre- and postnatal periods. The GR appears to be a major factor in brain maturation and in modulation of stress responses. In aged Brown Norway rat brain GR IR but not mineralocorticoid receptor (MR) IR is reduced in the hippocampal nerve cells. The intensity of GR IR but not the number of nerve cells is altered, indicating a reduced activation of the GR in aging in this rat strain. Overall GR participates in neuronal plasticity from fetal and postnatal life to adult life and aging.

Aging↗

Generalized presence of a PEC-60-like peptide in catecholamine neurones.

PEC-60, a 60-residue intestinal peptide structurally related to the pancreatic secretory type of trypsin inhibitor, has been isolated, characterized and molecularly cloned. It shows biological activity as a hormone in both the gastrointestinal tract and in the immune system. We now report immunohistochemical evidence suggesting its neural localization exclusively within central and peripheral catecholamine (CA) neurones. PEC-60-like immunoreactivity was present in cell bodies, dendrites and nerve terminals of virtually all catecholamine neurones examined and including the noradrenergic gland cells of the adrenal medulla. PEC-60-like immunoreactivity was not seen, however, within the tyrosine hydroxylase-positive but CA-negative arcuate neurones producing growth hormone releasing hormone. The findings open up the possibility that a PEC-60-like peptide may represent a generalized co-transmitter in the peripheral and central CA neurones.

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Evidence for a regional distribution of hyaluronic acid in the rat brain using a highly specific hyaluronic acid recognizing protein.

By means of a highly specific hyaluronic acid-recognizing protein the localization and regional distribution of hyaluronic acid was demonstrated in the tel- and diencephalon and in the midbrain of the adult rat nervous system. Histochemistry revealed labeling associated with the plasma membrane in highly discrete nerve cell bodies of the frontoparietal cortex, the red nucleus, the zona reticulata of the substantia nigra, the oculomotor nucleus and the reticular thalamic nucleus. A strong labeling without association with perikarya was demonstrated in the subgranular zone of the dentate gyrus of the hippocampal formation. The present results open up the possibility that the hyaluronic acid found in high concentrations associated with some perikarya may have a special role in plasticity responses in these discrete nerve cell populations.

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On the regional distribution of heparan sulfate proteoglycan immunoreactivity in the rat brain.

By means of two monoclonal antibodies specific for heparan sulfate (HS)-related epitopes, one (10E4) against native HS chains and one (3G10) against desaturated uronates, a highly regional and differential distribution of these two epitopes have been observed in the adult rat brain. The 10E4 epitope immunoreactivity (IR) is mainly found in the substantia nigra, the red nucleus and the subgranular zone of the dentate gyrus, while the 3G10 epitope IR is mainly found in the CA2 area of the hippocampal formation and the pyramdial cells in the layer V of the frontoparietal cortex. The codistribution of both types of IRs with basic fibroblast growth factor (bFGF, FGF-2) in neurons and astroglia supports the notion that heparan sulfate proteoglycans (HSPG) in the extracellular matrix may serve as a site for storage of bFGF and assist in the bFGF-induced activation of the high-affinity FGF receptors linked to astroglia and neurons in these discrete areas.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Basic fibroblast growth factor and steroid receptors in the aging hippocampus of the brown Norway rat: immunocytochemical analysis in combination with stereology.

The effect of aging on the hippocampal formation of the male Brown Norway rat was studied by immunohistochemistry and measurements of the immunoreactive hippocampal cells using stereological techniques. The total estimated number of glucocorticoid receptor (GR) immunoreactive neurons of the CA1-CA2 area did not differ in the 3- and the 36-month-old rat. However, the intensity of the GR immunoreactivity was decreased in the aged animals. A gradual decrease of the immunoreactivity for the mineralocorticoid receptor was also observed in the CA1-CA2 area. In the stratum oriens and the stratum radiatum of the CA1-CA2 area the immunoreactivity for basic fibroblast growth factor (bFGF) present in the glia was found to be reduced [20,000 +/- 2100 (n = 6)] in the 36-month-old rat vs the 3-month-old rat [28,500 +/- 4500 (n = 4) (*P = 0.05)]. However, there was no difference in the number of glial fibrillary acidic protein immunoreactive cells of this area in these two age groups. The present findings give evidence that in the Brown Norway rat there is no loss of the neuronal population containing glucocorticoid receptors of the CA1-CA2 area during aging but suggest that aging is characterized by deficits of glially derived growth factors, such as bFGF.

Aging↗

Basic fibroblast growth factor (bFGF, FGF-2) immunoreactivity exists in the noradrenaline, adrenaline and 5-HT nerve cells of the rat brain.

By means of two colour immunofluorescence procedures it has been possible to demonstrate in the rat brain the coexistence of TH and bFGF immunoreactivities (IRs) in the perikarya of large numbers of noradrenaline (NA) nerve cells of the locus coeruleus and of the NA cell groups A1, A5 and A7 and in many perikarya of the adrenaline (A) cell groups C1, C2 and C3. The coexistence of 5-hydroxytryptamine (5-HT) and bFGF IRs was demonstrated in the perikarya of large numbers of 5-HT nerve cells of practically all raphe nuclei. These results open up the possibility that bFGF may have a trophic role in the NA, A and 5-HT cell groups of the rat brain.

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Corticosterone increases FGF-2 (bFGF) immunoreactivity in the substantia nigra of the rat.

The effects of acute and subchronic (7 days) administrations of the adrenocortical hormone corticosterone on basic fibroblast growth factor (bFGF, FGF-2) immunoreactivity were studied in the substantia nigra of the rat by semiquantitative immunocytochemistry coupled with image analysis. Corticosterone was able to increase FGF-2 immunoreactivity in different nigral subregions and cell types (astrocytes and neurones) depending on the duration of the treatment. These results open up the possibility that stress hormones can modulate the trophic state of the substantia nigra through an action on FGF-2.

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Codistribution of choleratoxin binding sites and tyrosine hydroxylase/FGF-2 immunoreactive nigral nerve cells.

By means of light and confocal laser microscopical analysis of choleratoxin (CT) binding sites indicating the localization of the ganglioside GM1, evidence has been obtained for the presence of ganglioside GM1 in discrete nerve terminals, some of them identified by synapsin-1 immunoreactivity (IR), with a focal distribution in the nerve terminal membrane. Double immunolabelling studies demonstrate that GM1 positive nerve terminals are associated with tyrosine hydroxylase/fibroblast growth factor-2 (TH/FGF-2) immunoreactive dopamine (DA) perikarya in the zona compacta of the rat substantia nigra. It is suggested that GM1 may be released from these terminals to become incorporated into the nerve cell membrane of the FGF-2-containing DA nigral nerve cells, where they may enhance the activity of neurotrophic factor receptors such as those for FGF-2.

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Intramembrane interactions between neurotensin receptors and dopamine D2 receptors as a major mechanism for the neuroleptic-like action of neurotensin.

Evidence has been presented that behavioral actions of NT, inducing its neuroleptic-like action, can be explained on the basis of NT-D2 intramembrane receptor-receptor interactions in the basal ganglia, unrelated to the coexistence phenomenon, leading to reduced affinity and transduction of the D2 agonist binding site. By reducing selectively D2 receptor transduction at the pre- and postsynaptic level, the NT receptor appears capable of switching the DA synapses towards a D1 receptor-mediated transduction, illustrating how receptor-receptor interactions can increase the functional plasticity of central synapses (FIG. 12).

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Pancreatic galanin: molecular forms and anatomical locations.

Galanin-like immunoreactivity (GalLI) was found to be present in extracts taken from human, canine, and porcine pancreata. The dominant gel filtration peak in each species co-elutes with standard synthetic porcine galanin (Gal), but an apparently smaller molecular weight Gal form was present in human pancreas and intestine and in dog intestine. Reverse-phase HPLC demonstrated identity of porcine pancreatic Gal immunoreactivity with synthetic intestinal Gal. Heterogeneity was seen on reverse-phase HPLC: Human pancreas and intestine had three peaks of immunoreactivity; the retention times were identical between the pancreas and intestinal extracts; and human Gal elutes at an earlier retention time than porcine Gal. Similarly, dog pancreatic GalLI eluted earlier than porcine Gal on reverse-phase HPLC. Immunohistochemical studies revealed the presence of specific staining for GalLI in varicose nerve fibers in the pancreas of the three species. In the dog pancreas an association between Gal-containing nerve fibers and islet cells was readily demonstrable. This was not the case with pig or human pancreas. We conclude that pancreatic Gal is present in the pancreas of the three species and that molecular heterogeneity is similar between intestinal and pancreatic forms. In the dog, a distinct anatomical relationship is demonstrable between Gal-containing nerves and islet cells.

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Demonstration and nature of endothelin-3-like immunoreactivity in somatostatin and choline acetyltransferase-immunoreactive nerve cells of the neostriatum of the rat.

Using a rabbit endothelin-1 (ET-1) antiserum together with a goat-anticholineacetylase antiserum or a mouse anti-somatostatin antiserum it was possible by means of double immunolabelling procedures to demonstrate ET-like immunoreactivity in striatal nerve cell bodies of the rat, which were shown to contain either cholineacetylase or somatostatin immunoreactivity. Absorption studies with ET-3, ET-1 or big ET-1 indicated that the ET-like immunoreactivity was ET-3 like. In agreement the radioimmunoassay showed that ET-3-like immunoreactivity was present in higher concentrations than ET-1-like immunoreactivity in the neostriatum and other brain areas. Characterization by reversed phase HPLC revealed, however, that a major portion of the neostriatal ET-3-like immunoreactivity was not identical to ET-3. The nature of neuronal ET in the rat may thus be more complicated than hitherto assumed.

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Central peptidergic neurons as targets for glucocorticoid action. Evidence for the presence of glucocorticoid receptor immunoreactivity in various types of classes of peptidergic neurons.

By means of double immunolabeling procedures it has been possible to demonstrate glucocorticoid receptor (GR) immunoreactivity (IR) in large numbers of various peptidergic neurons of the brain including neurons containing gastrointestinal peptides, opioid peptides, and peptides with a hypothalamic hormone function. For each peptide system, however, marked heterogeneities exist among brain regions. Thus, in the neocortex and the hippocampal formation most of the brain peptide neurons lack GR IR, while the same types of peptide neurons in the arcuate and paraventricular nucleus [e.g. neuropeptide Y (NPY), somatostatin (SRIF) and the cholecystokinin (CCK) neurons] possess strong GR IR. Furthermore, in the arcuate, parvocellular part of the paraventricular nuclei and the central amygdaloid nucleus practically all the peptidergic neurons are strongly GR IR, while in the lateral hypothalamus, mainly the neurotensin (NT) and galanin (GAL) IR neurons are GR IR. These marked differences among areas probably reflect functional differences dependent upon their participation in stress regulated circuits. All the paraventricular NT, corticotropin-releasing factor (CRF), growth hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) and SRIF IR neurons appear to contain GR IR, while the luteinizing hormone-releasing hormone (LHRH) IR neurons lack GR IR, underlying the importance of glucocorticoids (GC) in controlling endocrine function. Finally, the GC may influence pain and mood control mainly via effects on enkephalin (ENK) neurons especially in the basal ganglia (mood) and on all beta-endorphin (beta-END) neurons of the arcuate nucleus, while most of the dynorphin neurons are not directly controlled by GC.

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Basic FGF is present in dopaminergic neurons of the ventral midbrain of the rat.

Immunocytochemistry procedures and 6-hydroxy-dopamine-induced degeneration of dopamine nerve cells provided evidence that practically all tyrosine hydroxylase immunoreactive (IR) neurons of the substantia nigra and ventral tegmental area contain cytoplasmic basic fibroblast growth factor immunoreactivity (bFGF IR), while many astroglial cells in the neostriatum and substantia nigra contain nuclear bFGF IR. RNA blot analysis demonstrated strong expression of a major 3.7 kb bFGF mRNA in the substantia nigra and ventral tegmental area. These results indicate that bFGF may be a significant growth factor in the DA neurons.

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Catecholaminergic systems in the brain of a gymnotiform teleost fish: an immunohistochemical study.

The localization of catecholamines (CA) in the brain of Apteronotus leptorhynchus was studied with immunohistochemical techniques using antibodies to the enzymes tyrosine hydroxylase (TH), dopamine B-hydroxylase (DBH), phenylethanolamine-N-methyltransferase (PNMT), and the neurotransmitter dopamine (DA). Telencephalic TH and DA immunoreactive (ir) neurons were located in the following structures: olfactory bulb, area ventralis telencephali partes ventralis, centralis, dorsalis, and intermediate. Diencephalic TH ir neurons were distributed in: nucleus preopticus periventricularis pars anterior, floor of preoptic recess, n. suprachiasmaticus, n. preopticus periventricularis pars posterior, n. anterior periventricularis, area ventralis lateralis, rostral region of posterior periventricular nucleus (paraventricular organ of other authors), periventricular nucleus of posterior tuberculum, n. recessus lateralis, n. tuberis lateralis pars anterior, and n. tuberis posterior. Although most diencephalic TH ir structures were also DAir, the posterior periventricular nucleus, n. recessus lateralis pars medialis, n. recessus posterioris, and ventral region of nucleus lateralis tuberis pars anterior showed differences in the distribution of TH and DA immunoreactivity. The rhombencephalic structures contained cell groups with different combinations of catecholamines as follows: TH and DBH ir neurons in the isthmic tegmentum (locus coeruleus); TH and DBH ir cells in the rostral medullary tegmentum ventral to VIIth nerve; TH and PNMT ir cells in the sensory nucleus of the vagus nerve; TH, DBH, and PNMT ir cells in the dorsal medullary tegmentum, TH and DBH ir cells in the dorsomedian postobecular region, ventral to the descending trigeminal tract and lateral to the central canal at medullospinal levels. This study shows that: (1) with few exceptions TH and DA ir coincides, (2) gymnotiforms possess similar DBH ir rhombencephalic groups, but additional telencephalic and rhombencephalic TH ir groups, and PNMT ir cells that were not reported previously in teleosts, and (3) the presence of CAergic fibers in the electrosensory system supports findings of their modulatory function in communication and aggression.

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Evidence for the existence of a population of arcuate neurons costoring choline acetyltransferase and tyrosine hydroxylase immunoreactivities in the male rat.

By combined immunoperoxidase and immunofluorescence histochemistry we have analyzed the distribution of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunoreactive (IR) perikarya within the same sections of the mediobasal hypothalamus of the male rat. Evidence was obtained for the existence of perikarya costoring TH and ChAT immunoreactivities in both the dorsomedial and ventrolateral part of the arcuate nucleus and in the adjacent periarcuate nucleus at all rostrocaudal levels. The results strongly implicate interactions between dopamine and acetylcholine as well as acetylcholine and growth hormone releasing factor in dorsomedially and ventrolaterally located TH/ChAT costoring tuberoinfundibular neurons, respectively.

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Ganglion cell arrangement and axonal trajectories in the anterior lateral line nerve of the weakly electric fish Apteronotus leptorhynchus (Gymnotiformes).

To determine the organizational principles underlying the peripheral electrosensory nervous system of weakly electric gymnotiform teleosts we labelled each of the four anterior lateral line nerve branches with HRP. We determined the position of labelled cell bodies within the ganglion and followed anterogradely filled fibers to their termination sites in one of the four somatotopic maps in the electroreceptive lateral line lobe (ELL). Within the ganglion, cell bodies exhibit a loose somatotopy based on nerve branch position: trunk electroreceptors have their cell bodies located in the caudal ganglion; cell bodies to the head receptors are rostral. Cell bodies to the head exhibit a rough dorsoventral polarity, supraorbital cells tend to be located dorsally, infraorbital cells centrally, and mandibular cells ventrally. Despite this general somatotopy there is substantial overlap (up to 30%) of cell bodies among regions. There appears to be no rostrocaudal topography within nerve branch regions. Iontophoretic WGA-HRP injected into the medial segment of the ELL retrogradely labelled cell bodies that innervate ampullary organs. These cell bodies were dispersed throughout the ganglion, indicating that cell bodies do not cluster by receptor type. Peripherally directed axons from the ganglion appear to undergo an active reorganization in order to form the nerve branches. Within nerve branches, axons to a particular area of skin do not cluster together. Centrally from the ganglion, axons retain the position of their cell body until they reach the ELL border. Once in the ELL, fibers become sorted in the deep fiber layer according to receptor type and the map they terminate in. This reorganization involves rearrangement of fascicles and axons within fascicles. In toto, proceeding from peripheral to central, the electrosensory periphery loses at least a portion of its receptor topography in the distal nerve and ganglion and then acquires both a functional and somatotopic organization after reaching the ELL; conceptually it is torn down and rebuilt again. From an ontogenetic perspective, axonal growth occurs from the ganglion outward; the fact that ganglion cell bodies are not highly organized while the receptors they innervate and their central processes are suggests that active axonal guidance mechanisms are involved.

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