Clinical Neuroscience - 2007;60(03-04)

Clinical Neuroscience

MARCH 20, 2007

[EFFECTS OF KETAMINE ON THE DEVELOPING CENTRAL NERVOUS SYSTEM]

VUTSKITS László, GASCON Eduardo, KISS Zoltán József

[Ketamine is a widely used drug in pediatric anesthesia practice, acting primarily through the blockade of the Nmethyl- D-aspartate (NMDA) type of glutamate receptors. A growing body of laboratory evidence, accumulated during the past few years, suggests that this drug could have potential adverse effects on the developing central nervous system. The goal of this short review is to give a brief synopsis of experimental work indicating ketamine-induced developmental neurotoxicity as well as to discuss potential limitations concerning extrapolation of these studies to clinical practice.]

Clinical Neuroscience

MARCH 20, 2007

[THE GHRELIN SYSTEM: PHYSIOPATHOLOGICAL INVOLVEMENT IN THE CONTROL OF BODY GROWTH AND ENERGY METABOLISM]

JACQUES Epelbaum

[This short review will summarize some recent findings on the physiopathology of the endogenous ghrelin/obestatin system by focussing on experimental studies aiming at blocking the effects of endogenous ghrelin and clinical studies investigating genotype/phenotype correlations concerning the genes encoding for ghrelin and its cognate receptor.]

Clinical Neuroscience

MARCH 20, 2007

[HUMAN TRYPSIN(OGEN) 4-LIKE IMMUNOREACTIVITY IN THE WHITE MATTER OF THE CEREBRAL CORTEX AND THE SPINAL CORD]

GALLATZ Katalin, MEDVECZKY Péter, NÉMETH Péter, SZILÁGYI László, GRÁF László, PALKOVITS Miklós

[Human brain trypsin(ogen) 4-like (HT-4) immunoreactivity was localized in glial cells of human cerebral cortex and spinal cord. After a short post mortem delay (two hours), cortical and spinal cord regions were dissected, frozen or immersed into a fixative solution. Sections of 10 and 50 µm thickness were cut and immunostained by antibodies raised against recombinant human trypsin 4. HT-4-like immunoreactive glial cells and fibers were stained in the white matter, low to moderate levels of immunostaining were also observed in the matrix of the cerebral cortex and the spinal cord. To characterize HT-4-like immunopositive glial cells, alternate sections were immunostained for astrocytes and oligodendrocytes. HT-4 is present predominantly in astrocytes, but some of the oligodendrocytes and microglial cells may also contain this enzyme.]

Clinical Neuroscience

MARCH 20, 2007

[USING BRAIN SLICE CULTURES OF MOUSE BRAIN TO ASSESS THE EFFECT OF GROWTH FACTORS ON DIFFERENTIATION OF BONE MARROW DERIVED STEM CELLS]

BRATINCSÁK András, LONYAI Anna, SHAHAR Tal, HANSEN Arne, TÓTH E. Zsuzsanna, MEZEY Éva

[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.]

Clinical Neuroscience

MARCH 20, 2007

[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.]

Clinical Neuroscience

MARCH 20, 2007

[ACTIVATED SOMATOSTATIN TYPE 2 RECEPTORS TRAFFIC IN VIVO FROM DENDRITES TO THE TRANS-GOLGI NETWORK]

CSABA Zsolt, PASCAL Dournaud

[Background and purpose - Understanding the trafficking of G-protein-coupled receptors is of particular importance. In the central nervous system, although some Gprotein- coupled receptors were reported to internalize in vivo, little is known about their trafficking downstream of the endocytic event. Methods - The distribution of the major somatostatin receptor subtype, the sst2, was monitored in the hippocampus using immunofluorescence from 10 minutes to seven days after in vivo injection of the receptor agonist octreotide. Results - From 10 min to 3 h after agonist injection, intensity of receptor immunoreactivity gradually decreased in the molecular layer of dentate gyrus and in the strata oriens and radiatum of CA1. Concomitantly, in the granular and pyramidal layers, small spherical immunofluorescent particles became apparent in perikarya, shortly after agonist stimulation (i.e. 30 min, 60 min). After longer survival times (i.e. 3 h, 6 h, 24 h), immunolabeling was confined to larger, intensely-stained intracytoplasmic vesicles. From 48 h to 7 d after agonist injection, distribution and intensity of sst2 receptor immunoreactivity became similar to that of control animals. The sst2 receptor labeling extensively colocalized with TGN38 and syntaxin 6 after OCT injection. Colocalization with trans-Golgi markers was observed as soon as 1 h after OCT injection and still present 24 h after. By contrast, colocalization with the endoplasmic reticulum marker PDI and the cis-Golgi marker GM130 was never observed. Conclusions - Our results suggest that upon agonist stimulation, dendritic receptors are retrogradely transported to a trans-Golgi network domain enriched in the t-SNARE syntaxin-6 and TGN38 proteins before recycling.]

Clinical Neuroscience

MARCH 20, 2007

[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

MARCH 20, 2007

[POSTNATAL EXPRESSION PATTERN OF DOUBLECORTIN (DCX) IN SOME AREAS OF THE DEVELOPING BRAIN OF MOUSE]

TAKÁCS József, ROBERTA Zaninetti, VÍG Julianna, VASTAGH Csaba, HÁMORI József

[We have investigated the spatio-temporal expression pattern of doublecortin (DCX) protein from postnatal day (P) 2 to postnatal day (P) 22 in the brain of developing mouse. We compared the expression of DCX in the rostral migratory stream (RMS) and dentate gyrus of the hippocampus (DG). Weak expression of DCX was detected in the RMS at P5, it became gradually stronger during the second postnatal week and reached its strongest expression by P18-P22. Moderate DCX immunostaining was present in the DG at P11, its marked expression - characteristic of newly generated neurons in the adult DG - appeared only after P22. Morphological and functional maturation was different in the RMS and DG, continuous neurogenesis appeared earlier in the RMS than in the DG.]

Clinical Neuroscience

MARCH 20, 2007

[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

MARCH 20, 2007

[OPTIMAL ALIGNMENT®. NOVEL SOFTWARE PROCEDURE FOR 3D RECONSTRUCTION OF ELECTRONMICROSCOPIC SERIAL SECTIONS]

SIMON László, GARAB Sándor, NOSZEK Annamária, ELIZABETH Römmer, ZÁBORSZKY László

[3D reconstruction from electronmicroscopic (EM) serial sections substantially differs from modeling body parts by linking convoluted planes delivered by CT and NMR. Namely, variations both in relative X-Y position and rotation of the target elements between the adjacent images and also additional problems caused by deformed, deteriorated or missing sections can only be overruled by an aligning paradigm, which exploits all the pixel-level information, and results in an optimal fitting with selected precision. This paper presents a complex computer program called Optimal Alignment®, which performs the precise elaboration of X-Y shift and relative rotation of two consecutive images. The required searching process will be customized by setting four independent parameters which relate the span and density of the pixel-scanning basic process. Optimalization of fitting accuracy versus running time can be achieved by a rather short training period. The potential precision of Optimal Alignment based on complex algorythms is far superior to manual aligning of EM photographs with the eye-wrist-mouse facility. The resulted database of alignment orientation parameters can serve as an advanced source for the 3D reconstructing programs. Optimal Alignment® software tool (supported by Hungarian Space Office grant TP 138) will be demonstrated on a basal forebrain NPY+ axonal reconstruction, performed in L. Záborszky’s laboratory (supported by NIH grant NSO23945).]

Clinical Neuroscience

MARCH 20, 2007

[THE SUPRASPINAL INNERVATION OF THE LEFT ADRENAL IS MORE INTENSE THAN THAT OF THE RIGHT ONE]

GERENDAI Ida, WIESEL Ory, BOLDOGKŐI Zsolt, TÓTH E. Ida

[Background and purpose - Previous studies using the viral transneuronal tracing technique demonstrated that central autonomic circuits are involved in the innervation of the adrenal gland. Since increasing number of data indicate laterality in the neuroendocrine system, we aimed to investigate whether the supraspinal innervation of the adrenal gland exhibits asymmetry or not. Methods - The central circuitry involved in the innervation of the left and the right adrenal gland was studied in individual rats by dual transneuronal tracing using isogenic recombinant strains (BDG and BDL) of Bartha strain of pseudorabies virus. Results - Viral infection of brain nuclei (dorsal vagal nucleus, nucleus of the solitary tract, caudal raphe nuclei, A5 cell group, hypothalamic paraventricular nucleus) from the left adrenal was more severe than that from the right organ. Dual-infected neurons from the two adrenals were also detected both in the brain stem and in the hypothalamus. Conclusion - The results indicate a predominance in the supraspinal innervation of the left adrenal gland. Data further suggest that each adrenal gland is innervated both by side-specific neurons and by neurons which project to both organs.]

Clinical Neuroscience

MARCH 20, 2007

[SALSOLINOL AND THE PERIPHERAL SYMPATHETIC ACTIVITY: THE EFFECTS OF HYPOPHYSECTOMY, ADRENALECTOMY AND ADRENAL MEDULLECTOMY]

SZÉKÁCS Dániel, BODNÁR Ibolya, NAGY M. György, FEKETE I.K. Márton

[The endogenous isoquinoline salsolinol (SALS) is a recently identified prolactin (PRL) releasing factor, a selective and potent stimulator of PRL secretion both in vivo and in vitro. SALS decreased the peripheral tissue dopamine (DA) level dose dependently, consequently increased the NE/DA ratio, indicating reduced release of newly formed norepinephrine (NE) from sympathetic terminals. The aim of our study was to investigate the effect of adrenal medullectomy (MEDX), adrenalectomy (ADX) and hypophysectomy (HYPOX) on the action of SALS on the PRL secretion, and on the catecholamine concentration of the selected sympathetically innervated peripheral tissues (atrium, spleen, etc). The experiments were done in male rats of 200-300 g body weight kept in air conditioned room with regular lighting. We used high-pressure liquid chromatography with electrochemical detection (HPLC-EC) for measurement of NE and DA concentrations, and radioimmunoassay for prolactin measurement. In MEDX as well as in ADX rats, SALS (25 mg/kg i.p.) was able to reduce DA level and increase the NE/DA ratio. The changes of prolactin secretion (increase by SALS) were not affected either by ADX or MEDX. Therefore the presence of the adrenal gland is not required for the changes of prolactin secretion, nor for the reduction of peripheral sympathetic activity induced by SALS. Investigating the possible effect of pituitary hormones on the peripheral sympathetic system, the action of SALS has been tested in HYPOX rats. We have found that the effect of SALS on peripheral sympathetic terminals is not affected by HYPOX, consequently the role of pituitary hormones in the effect of SALS on the peripheral catecholamine metabolism may be excluded.]

Clinical Neuroscience

MARCH 20, 2007

[SYNAPTIC CONNECTIONS OF GLUTAMATERGIC NERVE FIBRES IN THE RAT SUPRACHIASMATIC NUCLEUS]

KISS József, CSÁKI Ágnes, CSABA Zsolt, HALÁSZ Béla

[Background and purpose - The hypothalamic suprachiasmatic nucleus functioning as the principal circadian pacemaker in mammals, has a rich glutamatergic innervation. Nothing is known about the terminations of the glutamatergic fibres. The aim of the present investigations was to study the relationship between glutamatergic axon terminals and vasoactive intestinal polypeptide (VIP), GABA and arginine-vasopressin (AVP) neurons in the cell group. Methods - Double label immunocytochemistry was used and the brain sections were examined under the electron microscope. Vesicular glutamate transporter type 2 was applied as marker of the glutamatergic elements. Results - Glutamatergic fibers were detected in synaptic contact with GABAergic, VIP- and AVP-positive neurons forming asymmetric type of synapses. Conclusion - The findings are the first data on the synaptic contacts of glutamatergic axon terminals with neurochemically identified neurons in the suprachiasmatic nucleus.]

Clinical Neuroscience

MARCH 20, 2007

[ASSOCIATION OF APOLIPOPROTEIN E POLYMORPHISM WITH AGE-RELATED MACULAR DEGENERATION AND ALZHEIMER’S DISEASE IN SOUTH-WESTERN HUNGARY]

KOVÁCS Á. Katalin, PÁMER Zsuzsanna, KOVÁCS Attila, FEKETE Sándor, MISETA Attila, KOVÁCS Bálint, KOVÁCS L. Gábor

[Background - Age-related macular degeneration (AMD) and Alzheimer dementia (AD) show similarities (advanced age, formation of deposits of similar content). Recently apolipoprotein E 2 (apoE 2) has been associated with AMD, while apoE4 with AD. The question of coexistence, especially with respect to the genetic background has not been studied earlier. We investigated, therefore, the occurrence of AMD in AD patients and compared their lipid profile and apoE polymorphism. Methods - 49 AMD, 32 AD and 27 control patients were examined (risk factors, visual acuity, slit lamp biomicroscopy, fundoscopy). Following measurement of triglyceride, total and HDL cholesterol levels, apoE mutation analysis was performed. Results - AMD was found in 8% of the cooperating AD patients. The prevalence of the apoE 4 isoforms in the AMD, AD and the control patients was 2%, 47% and 22%, while that of apoE 2 was 17%, 6% and 7%, respectively. The prevalence of apoE 3 isoform was 82%, 41% and 71%, respectively. Triglyceride, total and HDL cholesterol were in the reference range; however, AD patients were characterized by a lower total cholesterol value. Conclusions - The new finding of this publication is the rare occurrence of AMD among AD patients. The higher frequency of apoE 4 among the AD population, and the higher frequency of apoE 2 among AMD patients in the South-Western region of Hungary confirms the findings of other investigators.]

Clinical Neuroscience

MARCH 20, 2007

[HISTOCHEMISTRY OF THE EXTRACELLULAR MATRIX IN THE SNAIL CENTRAL NERVOUS SYSTEM]

SERFŐZŐ Zoltán, ELEKES Károly

[Even tough the central nervous system (CNS) of gastropods has long been used as a model for studying different neuronal networks underlying behaviors, there is only little information on the molecular components of the extracellular matrix (ECM) of the nervous tissue. Therefore, the aim of the present study was to identify some of the ECM molecules by acid-base histochemistry. Staining with alcian blue at strong acidic pH, and with acridine orange at different pH and salt concentrations was carried out on cryostat sections taken from CNS preparations of adult specimens of the terrestrial snail, Helix pomatia, and the aquatic species, Lymnaea stagnalis, in order to visualize mild (carboxyl) and strong (sulphate) acidic groups, which are characteristic for different glucosaminoglycans. According to our findings, sulphated proteoglycans were abundant in the periganglionic sheath of both species, and they also occurred in the neuropil of Helix, whereas they were absent in Lymnaea. The interperikaryonal space contained mainly carboxyl residues, which might refer to the presence of hyaluronic acid. It is concluded that the ECM of the snail CNS, similarly to that in vertebrates, is partly composed of polymer macromolecules of different chemical properties. It is suggested that adaptation to environmental conditions and/or altered neuronal plasticity are responsible for the differences found in chemical characters of the ECM molecules between the two snail species.]

Clinical Neuroscience

MARCH 20, 2007

[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

MARCH 20, 2007

[GLUTAMATERGIC PHENOTYPE OF HYPOTHALAMIC NEUROSECRETORY SYSTEMS: A NOVEL ASPECT OF CENTRAL NEUROENDOCRINE REGULATION]

HRABOVSZKY Erik, LIPOSITS Zsolt

[While three decades ago, the co-existence of classical neurotransmitters and peptide neuromodulators in a single neuronal cell was considered to be rather exceptional, the phenomenon that neurons have a complex transmitter phenotype now appears to be the general rule. Parvicellular and magnocellular neurosecretory systems consist of neuronal cells which are specialized in secreting peptide neurohormones into the blood-stream to regulate hypophyseal functions. This mini-review, dedicated to the memory of Mariann Fodor, summarizes the current knowledge about the classical neurotransmitter content of different hypothalamic neurosecretory systems, with a special focus on the occurrence and putative functions of glutamate in parvicellular and magnocellular neurosecretory cells.]

Clinical Neuroscience

MARCH 20, 2007

[MOLECULAR ARCHITECTURE OF THE CANNABINOID SIGNALING SYSTEM IN THE CORE OF THE NUCLEUS ACCUMBENS]

MÁTYÁS Ferenc, WATANABE Masahiko, MACKIE Ken, KATONA István, FREUND F. Tamás

[Several abused drugs are known to alter glutamatergic signaling in reward pathways of the brain, and these plastic changes may contribute to the establishment of addiction- related behaviour. Glutamatergic synapses of the prefrontal cortical projections to the nucleus accumbens (nAcb) - which are suggested to be under endocannabinoid (eCB) control - play a central role in the addiction process. The most abundant eCB in the brain is 2-arachidonoyl- glycerol (2-AG). It is synthesized by diacylglycerol lipase alpha (DGL-α), and exerts its action via type 1 cannabinoid receptors (CB1). However, the precise localization of DGL-α and CB1 - i.e. the sites of synthesis and action of 2AG - is still unknown. At the light microscopic level, immunocytochemistry revealed a granular pattern of DGL-α distribution in the core of the nAcb. Electron microscopic analysis confirmed that these granules corresponded to the heads of dendritic spines. On the other hand, presynaptic axon terminals forming excitatory synapses on these spineheads were found to express CB1 receptors. Our results demonstrate that the molecular constituents for a retrograde endocannabinoid control of glutamatergic transmission are available in the core of the nAcb, and their relative subcellular location is consistent with a role of 2-AG in addiction-related plasticity of cortical excitatory synapses in this reward area.]

Clinical Neuroscience

MARCH 20, 2007

[IMMOBILIZATION INDUCED FOS EXPRESSION IN THE MEDIAL AND LATERAL HYPOTHALAMIC AREAS: A LIMITED RESPONSE OF HYPOCRETIN NEURONS]

KISS Alexander

[Induction of Fos, a proto-oncogene c-fos protein product, was immunohistochemically examined in the rat hypothalamic neurons 3 h after a single (1×120 min) or repeated (7×120 min) immobilization (IMO) stress. The aim of the present study was to reveal a possible parallelism in the cell activation between the medial and lateral hypothalamic neurons, especially between the stress responsive neurons in the hypothalamic paraventricular nucleus (PVN) and hypocretin (Hcrt) synthesizing neurons, i.e. suspected stress active neurons of the lateral hypothalamus. After IMO, the animals were perfused and their brains processed with immunohistochemistry for Fos or Fos/Hcrt proteins. Acute IMO elicited extensive Fos expression in both the examined areas. Excessive Fos expression was mainly seen in the PVN, while Hcrt neurons failed to show a broad response (appr. 5%) to single IMO. Clear occurrence of Fos signal was also seen in both hypothalamic areas of IMO-habituated rats. However, in these animals, in both areas examined, the number of Fos neurons was considerably suppressed, including the PVN. These results indicate that IMO is able to evoke a concurrent activation of Fos in many medial and lateral hypothalamic neurons. However, the scanty response of Hcrt neurons to acute IMO does not allow to assort them to a distinct IMO stress-responsive neuronal phenotypes of the brain.]

Clinical Neuroscience

MARCH 20, 2007

[THE ROLE OF VASOPRESSIN IN CHRONIC STRESS STUDIED IN A CHRONIC MILD STRESS MODEL OF DEPRESSION]

ZELENA Dóra, DOMOKOS Ágnes, BARNA István, CSABAI Katalin, BAGDY György, MAKARA B. Gábor

[Background and purpose - Vasopressin plays an important role in the hypothalamo-pituitary-adrenal axis regulation as well as in stress-related disorders. A common view suggested that the role of vasopressin is especially important during chronic stresses. Here we tested the hypothesis that vasopressin-deficient rats may be more resistant to the development of chronic hypothalamo-pituitary-adrenal axis hyperactivity after chronic mild stress. Methods - Male vasopressin deficient Brattleboro rats were compared to their heterozygous littermattes. Chronic mild stress consisted of different mild stimuli (e.g. wet cages, restraint) for 6 week. The corticosterone changes were followed by repeated tail cutting and organs and blood were collected from decapitated rats. Results - In controls, chronic mild stress resulted in symptoms of chronic stress state characterized by typical somatic (body weight reduction, thymus involution) and endocrine changes (resting plasma ACTH and corticosterone elevation and POMC mRNA elevation in anterior lobe of the pituitary). Unexpectedly, the lack of vasopressin could not influence any chronic mild stress-induced changes. Conclusion - Somatic changes and endocrine effects of chronic mild stress are similar in control and vasopressin deficient animals. This suggests that either vasopressin is not indispensable for activating the hypothalamo-pituitaryadrenal axis by chronic stress or the absence of vasopressin is compensated by other mediators (e.g. CRH) in Brattleboro rats.]

Clinical Neuroscience

MARCH 20, 2007

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

MOLNÁR Tünde, FEKETE Kútiné Erzsébet, KARDOS Julianna, PALKOVITS Miklós

[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.]

Clinical Neuroscience

MARCH 20, 2007

Clinical Neuroscience

MARCH 20, 2007

Clinical Neuroscience

MARCH 20, 2007

[FINE STRUCTURE OF THE AREA SUBPOSTREMA IN RAT. OPEN GATE FOR THE MEDULLARY AUTONOMIC CENTERS]

FODOR Mariann, PALKOVITS Miklós, GALLATZ Katalin

[The area subpostrema (ASP) is a V-shaped area, ventral and ventrolateral to the area postrema. It constitutes the upper border zone of the commissural portion of the nucleus of the solitary tract. The ASP is considered as a morphological and functional key area for the medullary autonomic center. The capillaries here, in contrast to the capillaries of the area postrema are not fenestrated but establish a specific staining for acetylcholinaestherase (AChE). The ASP contains a high density of fibers and terminals of several neuropeptides which are known to affect on NTS activity. Receptors of different neuropeptids and cathecholamines and a dense network of GFAP positive glial processes are found also here. The neurons and the glial cells of the ASP are connected with the AP and a bidirectional connection exists between the ASP and NTS.]

Clinical Neuroscience

MARCH 20, 2007

[PROJECTIONS OF VIP/PHI NEURONS OF THE INTERSTITIAL NUCLEUS OF CAJAL IN THE RAT]

FODOR Mariann, WILLIAM Rostène, ANNE Berod, BENCZE Viktória, PALKOVITS Miklós

[Neurons expressing VIP/PHI precursor mRNA have been localized in the interstitial nucleus of Cajal. Unilateral surgical cut through the medial forebrain bundle failed to influence VIP/PHI mRNA expression in the Cajal nucleus while brainstem hemisection or unilateral transection of the medial longitudinal fascicle reduced it markedly, ipsilateral to the knife cuts. Thus, in contrast to forebrain projecting VIP neurons in the rostral periaqueductal gray, VIP/PHI neurons in the Cajal nucleus project downwards, to the lower brainstem.]

Clinical Neuroscience

MARCH 20, 2007

[PITUITARY ATRIAL NATRIURETIC PEPTIDE OF PARAVENTRICULAR NUCLEUS ORIGIN]

FODOR Mariann, MAKARA B. Gábor, PALKOVITS Miklós

[Atrial natriuretic peptide-synthesizing neurons in the hypothalamic paraventricular nucleus constitute the major sources of ANP in the three lobes of the pituitary gland. Complete transection of the pituitary stalk eliminated 93% of ANP from the intermediate lobe, 47 and 77% from the anterior and the posterior lobes, respectively. Meantime, increased levels of immunoreactive ANP were measured in the median eminence, due to the accumulation of the peptide in the transected axons centrally to the transected stalk and in the paraventricular nucleus. It is likely that ANP neurons in the paraventricular nucleus innervate the pituitary, but those in the periventricular (median) preoptic nucleus and the organum vasculosum laminae terminalis may not contribute to the ANP innervation of the pituitary gland.]

Clinical Neuroscience

MARCH 20, 2007

[BRAIN INSULIN SIGNALLING IN THE REGULATION OF ENERGY BALANCE AND PERIPHERAL METABOLISM]

MICHAELA Diamant

[The unparalleled global rates of obesity and type 2 diabetes, together with the associated cardiovascular morbidity and mortality, are referred to as the "diabesity pandemic". Changes in lifestyle occurring worldwide, including the increased consumption of high-caloric foods and reduced exercise, are regarded as the main causal factors. Central obesity and insulin resistance have emerged as important linking components. Understanding the aetiology of the cluster of pathologies that leads to the increased risk is instrumental in the development of preventive and therapeutic strategies. Historically, skeletal muscle, adipose tissue and liver were regarded as key insulin target organs involved in insulinmediated regulation of peripheral carbohydrate, lipid and protein metabolism. The consequences of impaired insulin action in these organs were deemed to explain the functional and structural abnormalities associated with insulin resistance. The discovery of insulin receptors in the central nervous system, the detection of insulin in the cerebrospinal fluid after peripheral insulin administration and the well-documented effects of intracerebroventricularly injected insulin on energy homeostasis, have identified the brain as an important target for insulin action. In addition to its critical role as a peripheral signal integrating the complex network of hypothalamic neuropeptides and neurotransmitters that influence parameters of energy balance, central nervous insulin signalling is also implicated in the regulation of peripheral glucose metabolism. This review summarizes the evidence of insulin action in the brain as part of the multifaceted circuit involved in the central regulation of energy and glucose homeostasis, and discuss the role of impaired central nervous insulin signalling as a pathogenic factor in the obesity and type 2 diabetes epidemic.]