Clinical Neuroscience

[CHARACTERIZATION OF SPECIFIC SUCCINATE BINDING SITE IN BRAIN SYNAPTIC MEMBRANES]

MOLNÁR Tünde1, FEKETE Kútiné Erzsébet1, KARDOS Julianna1, PALKOVITS Miklós2

MARCH 20, 2007

Clinical Neuroscience - 2007;60(03-04)

[A synaptic receptor for gamma-hydroxybutyric acid (GHB) - a naturally occuring metabolite of succinic acid1 - interacting succinate has been disclosed in rat and human nucleus accumbens (NA) subcellular fractions2, but the molecular properties of this recognition site were not characterised. To address the presumed recognition site for succinate, the pharmacological profile of [3H]succinate binding to synaptic membranes prepared from rat forebrain and human NA samples has been investigated. Specific [3H]succinate binding sites in the human NA synaptic membrane fraction showed a strong pH-dependence and were characterized by binding of succinate (IC50,SUCC=2.9±0.6 µM), GHB (IC50,GHB=2.1±1.3 µM) and gap junction blocker carbenoxolone (IC50,CBX=7.1±5.8 µM). A similar [3H]succinate binding profile was found in rat forebrain synaptic membrane fractions. We conclude the existence of a pHo-dependent synaptic membrane binding site for the intermediary metabolite succinate. The pharmacological properties of this recognition site may possibly suggest the existence of a hemichannel-like target protein for succinate.]

AFFILIATIONS

  1. Department of Neurochemistry, Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest
  2. Neuromorphological and Neuroendocrine Research Laboratory, Hungarian Academy of Sciences and Semmelweis University, Budapest

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Clinical Neuroscience

[PROTECTIVE ACTION OF SNAKE VENOM NAJA NAJA OXIANA AT SPINAL CORD HEMISECTION]

ABRAHAMYAN S. Silva, MELIKSETYAN B. Irina, CHAVUSHYAN A. Vergine, ALOYAN L. Mery, SARKISSIAN S. John

[Based on data accumulated regarding the neuroprotective action of Proline-Rich-Peptide-1 (PRP-1, a fragment of neurophysin vasopressin associated hypothalamic glycoprotein consisting of 15 amino acid residues) on neurons survival and axons regeneration and taking into the account that LVV-Hemorphin-7 (LVV-H7, an opioid peptide, widely distributed in different cell types of various tissues of intact rats, including those of the nervous and immune systems) derived from the proteolitic processing of hemoglobin in response to adverse environmental and physiological conditions, possesses the anti-stressor properties, we used histochemistry, immunohistochemistry and electrophysiology to investigate the putative neuroprotective action of Central Asian Cobra Naja naja oxiana snake venom (NOX) on trauma-injured rats. ABC immunohistochemical method and histochemical method on detection of Ca2+- dependent acid phosphatase activity were used for the morpho-functional study. By recording the electrical activity of the signals from the single neurons in and below the SC injury place, NOX venom has been shown to result in the complete restoration of hypothalamic-spinal projections originated from ipsi- and contra-lateral PVN and SON to neurons of SC lumbar part. NOX prevented the scar formation, well observed two months after SC injury in the control rats, resulted in the regeneration of nerve fibers growing through the trauma region, survival of the PRP-1- and LVV-H7-immunoreactive (Ir) neurons, and increase of the PRP-1- and LVV-H7-Ir nerve fibers and astrocytes in the SC lesion region. NOX was suggested to exert the neuroprotective effect, involving the PRP-1 and LVV-H7 in the underlying mechanism of neuronal recovery.]

Clinical Neuroscience

[CENTRAL ATRIAL NATRIURETIC PEPTIDE IN DEHYDRATION]

BAHNER Udo, GEIGER Helmut, PALKOVITS Miklós, LENKEI Zsolt, LUFT C. Friedrich, HEIDLAND August

[To test the effect of dehydration on brain atrial natriuretic peptide (ANP) concentrations in areas important to salt appetite, water balance and cardiovascular regulation, we subjected rats to dehydration and rehydration and measured ANP concentration in 18 brain areas, as well as all relevant peripheral parameters. Water deprivation decreased body weight, blood pressure, urine volume, and plasma ANP, while it increased urine and plasma osmolality, angiotensin II, and vasopressin. ANP greatly increased in 17 and 18 brain areas (all cut cerebral cortex) by 24 h. Rehydration for 12 h corrected all changes evoked by dehydration, including elevated ANP levels in brain. We conclude that chronic dehydration results in increased ANP in brain areas important to salt appetite and water balance. These results support a role for ANP as a neuroregulatory substance that participates in salt and water balance.]

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[OXYGEN-GLUCOSE DEPRIVATION-INDUCED CHANGES IN ORGANOTYPIC CULTURES OF THE RAT HIPPOCAMPUS]

BALI Balázs, NAGY Zoltán, KOVÁCS J. Krisztina

[Introduction - (-)Deprenyl is an irreversible inhibitor of type B monoamine oxidase (MAO-B), which is now used for treatment of Parkinson’s or Alzheimer’s diseases. Evidence suggests that the neuroprotective effect of deprenyl may not be related exclusively to the inhibition of the enzyme MAO-B. Methods - To test the impact of deprenyl on ischemiainduced changes in vitro, we followed the time course of propidium iodide (PI) uptake as an indicator of neuronal cell death as well as the expression of apoptotic factors in organotypic hippocampal slice cultures exposed to oxygen- glucose deprivation (OGD) for 45 min. Results - The first signs of neuronal death were detected 2 hours after OGD and were extended to all subfields of the hippocampus by 24 hours post-injury. Presence of deprenyl (10-9 M) significantly delayed the cell death induced by the insult. Exposure of control cultures to deprenyl significantly increased the abundance of Bcl-2 and Bcl-xl mRNAs as revealed by RT-PCR. OGD resulted in an elevation of anti-apoptotic factors, while the expression of pro-apoptotic bax remained unchanged. Conclusion - These data suggest that deprenyl is neuroprotective in an in vitro model of ischemia. Although deprenyl upregulates the expression of Bcl-2 under basal conditions, its effect on anti-apoptotic factors is not significantly manifested during OGD.]

Clinical Neuroscience

[EFFECT OF LOCAL (INTRACEREBRAL AND INTRACEREBROVENTRICULAR) ADMINISTRATION OF TYROSINE HYDROXYLASE INHIBITOR ON THE NEUROENDOCRINE DOPAMINERGIC NEURONS AND PROLACTIN RELEASE]

BODNÁR Ibolya, HECHTL Dániel, SZÉKÁCS Dániel, OLÁH Márk, NAGY M. György

[Background and purpose - Hypothalamic dopamine (DA), the physiological regulator of pituitary prolactin (PRL) secretion, is synthesized in the neuroendocrine DAergic neurons that projects to the median eminence and the neurointermediate lobe of the pituitary gland. The rate-limiting step of DA biosynthesis is catalyzed by the phosphorylated, therefore activated, tyrosine hydroxylase (TH) that produces L-3,4-dihydroxy- phenylalanine from tyrosine. The aims of our present study were to investigate 1. the effect of local inhibition of the DA biosynthesis in the hypothalamic arcuate nucleus on PRL release, and to get 2. some information whether the phosphorylated TH is the target of enzyme inhibition or not. Methods - A TH inhibitor, α-methyl-p-tyrosine was injected either intracerebro-ventricularly or into the arcuate nucleus of freely moving rats and plasma PRL concentration was measured. Immunohistochemistry, using antibodies raised against to native as well as phosphorylated TH were used to compare their distributions in the arcuate nucleus-median eminence region. Results - Intracerebro-ventricular administration of α-methyl-p-tyrosine has no effect, unlike the intra-arcuatus injection of enzyme inhibitor resulted in a slight but significant elevation in plasma PRL. Parallel with this, the level of DA and DOPAC were reduced in the neurointermediate lobe while no change in norepinephrine concentration can be detected indicating a reduced biosynthesis of dopamine following TH inhibition. On the other hand, systematic application of the α-methyl-p-tyrosine that inhibits TH activity located in DA terminals of the median eminence and the neurointermediate lobe, resulted in the most significant elevation of PRL. Conclusion - Our results suggest that α-methyl-p-tyrosine administered close to the neuroendocrine DAergic neurons was able to inhibit only a small proportion of the TH. Moreover, it also indicate that the majority of the activated TH can be found in the axon terminals of DAergic neurons, therefore, the DA released into the pituitary portal circulation is synthesized at this site.]

Clinical Neuroscience

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[Bone marrow derived stem cells (BMDSCs) have been reported to form neurons and supportive cells in the brain. We describe a technique that combines the simplicity of in vitro studies with many of the advantages of in vivo experiments. We cultured mouse brain slices, deposited GFPtagged BMDSCs evenly distributed on their surfaces, and then added test factors to the culture medium. Addition of both SDF-1 and EGF resulted in morphological changes of BMDSC and in the induction of islet-1, a marker of neuroepithelial progenitors. We conclude that organotypic tissue culture (OTC) may allow us to detect the effects of exogenous factors on the differentiation of BMDSCs (or any other type of stem cells) in an environment that may resemble the CNS after brain injury. Once such factors have been identified they could be evaluated for tissue regeneration in more complex, whole animal models.]

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Clinical Neuroscience

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