Search PubMed⌕ Search

Biomedical subjects

E Battenberg

Publications and source records attributed to E Battenberg.

At least 19 recordsLinked to original sources
PubMed1998

Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord.

The cellular distribution of the type 3 serotonin receptor (5HT3R) in the rat brain was established immunocytochemically by using a polyclonal antibody raised against a synthetic peptide from the deduced amino-acid sequence of the cloned 5HT3R. The 5HT3R-immunoreactive neurons were found in the forebrain, brainstem, and spinal cord, but within each region, the intensity of the immunoreactivity differed considerably. Within the forebrain, intensely immunoreactive cells were found in layers II-III of the neocortex, anterior olfactory nucleus, hippocampal formation, and amygdala. A few strongly immunoreactive neurons were consistently observed in the caudate putamen, and moderately or weakly labeled neurons were occasionally found in the nucleus accumbens. Within the brainstem, intensely labeled neurons were found in the trigeminal motor (V) and facial (VII) nuclei. Immunostained neurons were detected in the dorsal and the ventral horn of the spinal cord. These results reveal that the 5HT3R-immunoreactive neurons are broadly distributed throughout the rat brain and spinal cord, and suggest that this receptor can subserve significant participation in central nervous system neurotransmission.

Animals↗
PubMed1996

SNAP-25 and synaptotagmin involvement in the final Ca(2+)-dependent triggering of neurotransmitter exocytosis.

In neurons, depolarization induces Ca2+ influx leading to fusion of synaptic vesicles docked at the active zone for neurotransmitter release. While a number of proteins have now been identified and postulated to participate in the assembly and subsequent disengagement of a vesicle docking complex for fusion, the mechanism that ultimately triggers neuroexocytosis remains elusive. Using a cell-free, lysed synaptosomal membrane preparation, we show that Ca2+ alone is sufficient to trigger secretion of glutamate and furthermore that Ca(2+)-signaled exocytosis is effectively blocked by antibodies and peptides to SNAP-25, a key constituent of the vesicle docking complex. In addition, Ca2+ inhibits the ability of synaptotagmin, a synaptic vesicle protein proposed as a calcium sensor and triggering device, to associate with this docking complex. These results support a model in which Ca(2+)-dependent triggering of neurotransmission at central synapses acts after ATP-dependent potentiation of the docking-fusion complex for membrane fusion.

Adenosine Triphosphate↗
PubMed1996

The type 3 serotonin receptor is expressed in a subpopulation of GABAergic neurons in the rat neocortex and hippocampus.

We used in situ hybridization and immunocytochemistry to investigate the presence of GABA in neurons that express the type 3 serotonin receptor (5-HT3R). Quantitative analysis indicated that more than 90% of 5-HT3R expressing cells are GABAergic in the neocortex and hippocampus. The co-existence of 5-HT3R and GABA in cortical and hippocampal neurons indicates that serotonin, via 5-HT3R, can affect GABA release and suggests the participation of 5-HT3R in the inhibitory regulation of forebrain neurons.

Amygdala↗
PubMed1996

Cellular and subcellular immunolocalization of the type 3 serotonin receptor in the rat central nervous system.

We developed and characterized 14 polyclonal antibodies against peptides whose sequences were predicted from the type 3 serotonin receptor subunit A (5-HT3R-A) cDNA. One such antiserum, 0165, raised against a peptide corresponding to the large putative intracellular loop, immunoprecipitated in vitro translated 5-HT3R-A protein and recognized both recombinant and neuronal 5-HT3R-A protein by Western blot at a high titer. Furthermore, when antiserum 0165 was used to immunolabel brain sections previously hybridized with a riboprobe specific for 5-HT3R-A transcripts, neuronal co-localization of immunoproduct and transcript was widely found throughout the brain. The study of the distribution of 5-HT3R-A-immunoreactivity in the rat central nervous system with antiserum 0165 revealed intensely immunolabeled neurons in the forebrain (isocortex, olfactory regions, hippocampal formation and amygdala), brainstem (sensory and motor nuclei and nuclei of the reticular formation) and spinal cord (dorsal and ventral horn). At the subcellular level, the 5-HT3R-A was found in endomembranes involved in translation (nuclear envelope and endoplasmic reticulum) and in the dendritic plasma-membrane. The present report is the first description of the 5-HT3R-A immunolocalization in the CNS. The wide distribution of the 5-HT3R-A in the brain and spinal cord based on ligand binding, in situ hybridization and immunolocalization studies support its participation in a large array of central nervous system functions.

Animals↗
PubMed1996

Learning impairment in transgenic mice with central overexpression of corticotropin-releasing factor.

The present studies were designed to test the learning and memory capacities of transgenic mice with central overexpression of corticotropin-releasing factor in a forced alternation water T-maze task and in the Morris water maze. In T-maze testing, littermate control mice reached a criterion of 70% correct responses after five days of trials, while the performance of transgenic subjects was still random after the same training. In Morris maze testing, control subjects reached the submerged platform significantly faster (F(1.48) = 4.51, P < 0.05) after three days of trials, while the performance of transgenic mice was unimproved over the same period. The deficit in Morris maze performance in transgenic mice was reversed when the platform was visible above the surface of the water. Pre-test administration of the benzodiazepine anxiolytic, chlordiazepoxide (10 mg/kg), before acquisition training also produced a significant (F(4.40) = 16.61, P < 0.001) and persistent improvement in Morris maze performance in transgenic mice when compared to vehicle-treated transgenic litter mates. Finally, there was no evidence of hippocampal cell loss in transgenic brains. The results suggest that corticotropin-releasing factor-overexpressing mice exhibit a profound learning deficit without sensory or motor-related impairments, and that memory plasticity can be restored by anxiolytic pre-treatment. Thus, constitutive overabundance of brain corticotropin-releasing factor may produce hyperemotionality that interferes with learned behaviors. Stress-related disorders characterized by co-morbid deficits in learning/memory may benefit from pharmacological normalization of brain corticotropin-releasing factor systems.

Animals↗
PubMed1990

Parvalbumin immunoreactivity in the rat retina.

The distribution of the Ca2+ binding protein parvalbumin was studied in the rat retina with immunocytochemistry using a mouse monoclonal antibody. Specific parvalbumin immunoreactivity was identified within a subpopulation of ganglion cells and a subpopulation of amacrine cells. The topographical data provided by the present study may serve as a basis for a functional characterization of parvalbumin's role in the nervous system.

Animals↗
PubMed1990

Identification of two nerve growth factor-induced polypeptides in PC12 cells.

We have identified two nerve growth factor (NGF)-induced polypeptides (Mr 80,000 and 90,000) in PC12 cells that are heat stable and not sulfated. Indirect immunofluorescence localization of these polypeptides in NGF-treated PC12 cells reveals a punctate pattern concentrated in neurites. Immunoperoxidase staining of rat tissue shows that these polypeptides are found throughout the brain in selected subsets of neurons and are absent in the pituitary or adrenal medulla. Several of these characteristics are similar to a recently described NGF-induced secretory protein (VGF8a), which has sequence similarities to secretogranins. The property of NGF inducibility and the distribution of these polypeptides within rat tissues are both novel features for secretogranin proteins.

Adrenal Gland Neoplasms↗
PubMed1990

Transgenic mice expressing beta-galactosidase in mature neurons under neuron-specific enolase promoter control.

To gain insights into transcription factors defining neuronal identity, we generated transgenic mice carrying a 1.8 kb rat neuron-specific enolase (NSE) promoter fragment fused to an E. coli lacZ gene. Four of seven transgenic families expressed transgene RNA in the nervous system but not in most other tissues. Histochemical analysis of adult brain from the two lines with highest lacZ mRNA levels showed neuron-specific, pan-neuronal beta-galactosidase activity. Developmental RNA and histochemical analyses showed parallel onset of transgene and endogenous NSE gene expression in various neuronal cell types, although the magnitude of NSE mRNA accumulation later in development was not matched by the transgene. These results suggest that cis-acting regulatory elements, subject to neuron-specific control, are located within 1.8 kb upstream from the NSE gene.

Animals↗
PubMed1989

Nucleotide sequence and cellular distribution of rat chromogranin B (secretogranin I) mRNA in the neuroendocrine system.

The mRNA of rat secretory-vesicle protein chromogranin B is abundant in brain, adrenal medulla, and anterior pituitary. The primary translation product predicted from the cDNA sequence of this 2,337-nucleotide transcript corresponds to a hydrophilic 655-residue protein preceded by a signal peptide. Both termini of the mature 75-kD protein show extensive similarity to other chromogranins; the more variable internal region is characterized by glutamic acid clusters and numerous pairs of basic residues. In rodent brain, mRNA accumulation starts around embryonic days 13-14 and peaks by postnatal day 20. In situ hybridization in brain sections shows that the mRNA is enriched in the hippocampal formation, the endocrine hypothalamus, the olfactory system, and in anatomically distinct structures in the pons-medulla.

Amino Acid Sequence↗
PubMed1989

The identification of a novel synaptosomal-associated protein, SNAP-25, differentially expressed by neuronal subpopulations.

cDNA clones of a neuronal-specific mRNA encoding a novel 25-kD synaptosomal protein, SNAP-25, that is widely, but differentially expressed by diverse neuronal subpopulations of the mammalian nervous system have been isolated and characterized. The sequence of the SNAP-25 cDNA revealed a single open reading frame that encodes a primary translation product of 206 amino acids. Antisera elicited against a 12-amino acid peptide, corresponding to the carboxy-terminal residues of the predicted polypeptide sequence, recognized a single 25-kD protein that is associated with synaptosomal fractions of hippocampal preparations. The SNAP-25 polypeptide remains associated with synaptosomal membrane components after hypoosmotic lysis and is released by nonionic detergent but not high salt extraction. Although the SNAP-25 polypeptide lacks a hydrophobic stretch of residues compatible with a transmembrane region, the amino terminus may form an amphiphilic helix that may facilitate alignment with membranes. The predicted amino acid sequence also includes a cluster of four closely spaced cysteine residues, similar to the metal binding domains of some metalloproteins, suggesting that the SNAP-25 polypeptide may have the potential to coordinately bind metal ions. Consistent with the protein fractionation, light and electron microscopic immunocytochemistry indicated that SNAP-25 is located within the presynaptic terminals of hippocampal mossy fibers and the inner molecular layer of the dentate gyrus. The mRNA was found to be enriched within neurons of the neocortex, hippocampus, piriform cortex, anterior thalamic nuclei, pontine nuclei, and granule cells of the cerebellum. The distribution of the SNAP-25 mRNA and the association of the protein with presynaptic elements suggest that SNAP-25 may play an important role in the synaptic function of specific neuronal systems.

Amino Acid Sequence↗
PubMed1986

The brain-specific gene 1B236 is expressed postnatally in the developing rat brain.

The rat brain-specific polypeptide 1B236 was previously characterized by molecular cloning and nucleotide sequence determination of its mRNA. It has been shown to exist in rat brain in discrete neuronal circuits, primarily as a 100,000 Da glycoprotein. We now have determined the time course of expression of 1B236 mRNA and protein in rat brain during fetal and postnatal development, detecting 1B236 mRNA by RNA blotting and assaying 1B236 protein by electroblotting and radioimmunoassay with antibodies against synthetic peptides. By both indices, expression of the 1B236 gene products is found to be a relatively late event in neuronal development. 1B236 mRNA is first detectable in extracts of whole rat brain at Postnatal Day 5 (PD 5) and increases to a maximum concentration at PD 25. In extracts of dissected brain regions, 1B236 mRNA is first detectable at PD 5 in hindbrain and cerebellum, at PD 9 in midbrain/diencephalon, but not until PD 13 in telencephalon. The appearance of 1B236 protein follows a very similar time course to that of its mRNA in both whole brain and dissected brain regions, suggesting that the expression of the protein during development is regulated largely by transcription of its mRNA. The pattern of 1B236 expression was confirmed by immunocytochemical localization of 1B236 protein: Immunoreactive material can be detected first in spinal cord at PD 3-PD 5 and then appears in progressively more rostral brain regions in increasingly older animals. Several brain regions, however, that do not contain 1B236 immunoreactivity in the adult, such as optic nerve and somatic efferent cranial nerve nuclei, show transient expression of 1B236 during postnatal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Regional distribution of endorphin, Met5-enkephalin and Leu5-enkephalin in the pigeon brain.

The distribution of beta-endorphin and enkephalin in the pigeon forebrain by immunohistochemistry and radioimmunoassay is essentially analogous to mammals. Both endorphin- and enkephalin-reactive fibers have a similar periventricular distribution, but the enkephalin fibers are more extensive and are also found in the paleostriatum, limbic regions and brain stem, pituitary stalk and notably, penetrating the organum vasculosum hypothalami. There was poor correlation between endorphin and enkephalin regional contents by radioimmunoassay. In contrast, a highly significant correlation was observed between Met5-enkephalin and Leu5-enkephalin regional distribution. These data support the view that enkephalin neurons and endorphin neurons are independent central neuronal systems.

Animals↗
PubMed1979

Widespread distribution of protein I in the central and peripheral nervous systems.

Protein I, a naturally occurring substrate for cyclic AMP-dependent and calcium-dependent protein kinases, previously has been found only in mammalian brain, where it has been demonstrated to be located in neurons. Various tissues and organs outside the brain have now been examined for the possible occurrence of protein I, by using both an immunohistochemical approach and a chemical procedure involving radioimmunolabeling of polyacrylamide gels. Protein I has been found in the inner plexiform layer of the retina, in the posterior pituitary, and in the autonomic nervous system. In tissue composed predominantly of cells other than nerve cells, immunoreactivity was present only where innervation was present. Protein I appeared to be localized in some, but not all, nerve terminals and synapses.

Animals↗
PubMed1979

Immunocytochemical localization, in synapses, of protein I, an endogenous substrate for protein kinases in mammalian brain.

Protein I is a principal endogenous substrate for cyclic AMP- and Ca2+-dependent protein kinases of mammalian brain. Antibodies raised against purified protein I have been used to localize this protein in the rat central nervous system. At the light microscope level, immunoreactivity was detected in punctate deposits in selected zones of synaptic termination. These deposits varied in density among brain regions. At the electron microscope level, immunoreactivity was observed at some but not all synaptic regions and was restricted to the perimeter of synaptic vesicles and to submembranous material in the postsynaptic neuron.

Animals↗