Inhibitors of the NMDA-Nitric Oxide Signaling Pathway Protect Against Neuronal Atrophy and Synapse Loss Provoked by l-alpha Aminoadipic Acid-treated Astrocytes.


:The impact of treating astrocytes with the astrocytic toxin l-alpha amino adipic acid (L-AAA) on neuronal outgrowth, complexity and synapse formation was assessed, using a model of astrocyte-neuronal interaction. Treatment of rat primary cortical neurons with conditioned media (CM) derived from astrocytes treated with L-AAA reduced neuronal complexity and synapse formation. L-AAA provoked a reduction in the expression of glial fibrillary acid protein (GFAP) and a reduction in ATP-linked mitochondrial respiration in astrocytic cells. As the NMDA-R/PSD-95/NOS signaling pathway is implicated in regulating the structural plasticity of neurons, treatment of neuronal cultures with the neuronal nitric oxide synthase (nNOS) inhibitor 1-[2-(trifluoromethyl)phenyl] imidazole (TRIM) [100 nM] was assessed and observed to protect against L-AAA-treated astrocytic CM-induced reduction in neuronal complexity and synapse loss. Treatment with the NMDA-R antagonist ketamine protected against the CM-induced loss of synapse formation whereas the novel PSD-95/nNOS inhibitors 2-((1H-benzo[d] [1,2,3]triazol-5-ylamino) methyl)-4,6-dichlorophenol (IC87201) and 4-(3,5-dichloro-2-hydroxy-benzylamino)-2-hydroxybenzoic acid (ZL006) protected against synapse loss with partial protection against reduced neurite outgrowth. Furthermore, L-AAA delivery to the pre-limbic cortex (PLC) of mice was found to increase dendritic spine density and treatment with ZL006 reduced this effect. In summary, L-AAA-induced astrocyte impairment leads to a loss of neuronal complexity and synapse loss in vitro and increased dendritic spine density in vivo that may be reversed by inhibitors of the NMDA-R/PSD-95/NOS pathway. The results have implications for understanding astrocytic-neuronal interaction and the search for drug candidates that may provide therapeutic approaches for brain disorders associated with astrocytic histopathology.






David J,O'Toole E,O'Reilly K,Thuery G,Assmann N,Finlay D,Harkin A




Has Abstract


2018-11-10 00:00:00












  • Physiological effects of chronic and acute application of N-methyl-D-aspartate and 5-amino-phosphonovaleric acid to the optic tectum of Rana pipiens frogs.

    abstract::Visually elicited activity contributes to the formation of orderly connections in the optic tectum of frogs. Glutamate receptors of the N-methyl-D-aspartate class participate in this process. Blocking those receptors interferes with activity-dependent refinement of maps in normal frogs and of ocular dominance bands in...


    pub_type: 杂志文章


    authors: Udin SB,Scherer WJ,Constantine-Paton M

    更新日期:1992-08-01 00:00:00

  • Vagal modulation of responses elicited by stimulation of the aortic depressor nerve in neurons of the rostral ventrolateral medulla oblongata in the rat.

    abstract::Stimulation of cervical vagal afferents inhibits central sympathetic outflows in part by inhibiting the ongoing activity of putative baroreceptive neurons in the rostral ventrolateral medulla oblongata. The aim of the present study was to examine the electrophysiological characteristics of vagal responses and their in...


    pub_type: 杂志文章


    authors: Zagon A,Rocha I,Ishizuka K,Spyer KM

    更新日期:1999-01-01 00:00:00

  • Postnatal decrease in transforming growth factor alpha is associated with enlarged ventricles, deficient amygdaloid vasculature and performance deficits.

    abstract::It is well established that transforming growth factor alpha is involved prenatally in development of the nervous system, but its role in the postnatal brain is less well understood. Here, we document the occurrence of late-onset, morphological and behavioral deficits in the naturally occurring murine mutant, Waved-1 ...


    pub_type: 杂志文章


    authors: Burrows RC,Levitt P,Shors TJ

    更新日期:2000-01-01 00:00:00

  • Cell density increases Bcl-2 and Bcl-x expression in addition to survival of cultured cerebellar granule neurons.

    abstract::The proto-oncogene bcl-2 and its family members, bcl-x and bax are recognized as major regulators of cell death and survival. Although Bcl-2 and Bcl-x are expressed in brain, little is known how they are regulated in neurons. Here we have studied the expression of bcl-2, bcl-xL and bax mRNA in rat cerebellar granule n...


    pub_type: 杂志文章


    authors: Ohga Y,Zirrgiebel U,Hamnér S,Michaelidis TM,Cooper J,Thoenen H,Lindholm D

    更新日期:1996-08-01 00:00:00

  • Vasoactive intestinal polypeptide/peptide histidine isoleucine immunoreactive neuron systems in the basal hypothalamus of the rat with special reference to the portal vasculature: an immunohistochemical and in situ hybridization study.

    abstract::Using immunohistochemistry and in situ hybridization, we have analysed the distribution of vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) in hypothalamus of male and female Sprague-Dawley rats under normal and experimental conditions. In most cases there was a good overlap between the d...


    pub_type: 杂志文章


    authors: Ceccatelli S,Fahrenkrug J,Villar MJ,Hökfelt T

    更新日期:1991-01-01 00:00:00

  • Characteristics and specific localization of receptors for atrial natriuretic peptides at non-neuronal cells in cultured mouse spinal cord cells.

    abstract::Characteristics of atrial natriuretic peptide receptors were determined in cultured mouse spinal cord cells. Saturation and competition experiments demonstrated the presence of a single class of atrial natriuretic peptide binding sites with high affinity (KD = 0.054 nM) and a density of 1.92 fmoles/10(6) cells. A simi...


    pub_type: 杂志文章


    authors: Simonnet G,Allard M,Legendre P,Gabrion J,Vincent JD

    更新日期:1989-01-01 00:00:00

  • The organization of the ipsi- and contralateral claustrocortical system in rat with notes on the bilateral claustrocortical projections in cat.

    abstract::The organization of the claustrocortical system was investigated in rat by means of cortical injections of either lectin-conjugated horseradish peroxidase or retrograde fluorescent tracers. The latter were also employed in cat. Evans Blue, Fast Blue, True Blue, Nuclear Yellow and Diamidino Yellow were used in differen...


    pub_type: 杂志文章


    authors: Minciacchi D,Molinari M,Bentivoglio M,Macchi G

    更新日期:1985-11-01 00:00:00

  • Kainic acid induced seizures: changes in somatostatin, substance P and neurotensin.

    abstract::The neuropeptides somatostatin, neurotensin and substance P were investigated in rats during and after limbic seizures induced by systemic injection of kainic acid (10 mg/kg, i.p.). Three hours after injection of the toxin, pronounced decreases (40-50%) in somatostatin-like immunoreactivity in frontal cortex, striatum...


    pub_type: 杂志文章


    authors: Sperk G,Wieser R,Widmann R,Singer EA

    更新日期:1986-04-01 00:00:00

  • Midbrain muscarinic receptors modulate morphine-induced accumbal and striatal dopamine efflux in the rat.

    abstract::Midbrain dopamine neurons are critical in mediating the rewarding effects of opiates in dependent rats, as well as modulating some manifestations of opiate withdrawal. Morphine is known to excite dopamine neurons and thereby facilitate forebrain dopamine transmission through inhibition of GABA neurons. Cholinergic neu...


    pub_type: 杂志文章


    authors: Miller AD,Forster GL,Yeomans JS,Blaha CD

    更新日期:2005-01-01 00:00:00

  • Associations Between Delay Discounting and Connectivity of the Valuation-control System in Healthy Young Adults.

    abstract::The process of valuation assists in determining if an object or course of action is rewarding. Delay discounting is the observed decay of a rewards' subjective value over time. Encoding the subjective value of rewards across a spectrum has been attributed to brain regions belonging to the valuation and executive contr...


    pub_type: 杂志文章


    authors: Loganathan K,Lv J,Cropley V,Ho ETW,Zalesky A

    更新日期:2021-01-01 00:00:00

  • Characterization of GABA release from intrastriatal striatal transplants: dependence on host-derived afferents.

    abstract::Extracellular levels of GABA, derived from cell suspension transplants of embryonic day 14-15 rat striatal primordia implanted into the previously excitotoxically lesioned striatum, were measured using intracerebral microdialysis in halothane-anaesthetized rats. GABA overflow was monitored using loop type dialysis pro...


    pub_type: 杂志文章


    authors: Campbell K,Kalén P,Wictorin K,Lundberg C,Mandel RJ,Björklund A

    更新日期:1993-03-01 00:00:00

  • A peripheral cannabinoid mechanism suppresses spinal fos protein expression and pain behavior in a rat model of inflammation.

    abstract::The present studies were conducted to test the hypothesis that systemically inactive doses of cannabinoids suppress inflammation-evoked neuronal activity in vivo via a peripheral mechanism. We examined peripheral cannabinoid modulation of spinal Fos protein expression, a marker of neuronal activity, in a rat model of ...


    pub_type: 杂志文章


    authors: Nackley AG,Suplita RL 2nd,Hohmann AG

    更新日期:2003-01-01 00:00:00

  • Moderate hypoglycemia aggravates effects of hypoxia in hippocampal slices from diabetic rats.

    abstract::We recorded the effects of hypoxia combined with relative hypoglycemia on pre- and post-synaptic potentials in the CA1 area of slices from 4-month-old control and diabetic (streptozotocin-treated) Wistar rats. In experiments on slices kept in 10 or 4 mM glucose (at 33 degrees C), hypoxia was applied until the pre-syna...


    pub_type: 杂志文章


    authors: Tekkök SB,Godfraind JM,Krnjević K

    更新日期:2002-01-01 00:00:00

  • Ovarian steroid regulation of the midbrain corticotropin releasing factor and urocortin systems in macaques.

    abstract::A significant number of postmenopausal women report increased anxiety and vulnerability to stress, which has been linked to decreased secretion of ovarian steroids. Communication between the serotonin system and the corticotropin releasing factor (CRF) system determines stress sensitivity or resilience. This study exa...


    pub_type: 杂志文章


    authors: Sanchez RL,Reddy AP,Bethea CL

    更新日期:2010-12-15 00:00:00

  • Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis.

    abstract::In mice, microRNAs (miRNAs) are required for embryonic viability, and previous reports implicate miRNA participation in brain cortical neurogenesis. Here, we provide a more comprehensive analysis of miRNA involvement in cortical brain development. To accomplish this we used mice in which Dicer, the RNase III enzyme ne...


    pub_type: 杂志文章


    authors: McLoughlin HS,Fineberg SK,Ghosh LL,Tecedor L,Davidson BL

    更新日期:2012-10-25 00:00:00

  • Evidence of functional vitamin D receptors in rat hippocampus.

    abstract::The steroid hormone vitamin D has important biological roles in calcium transport, cell growth, and cell differentiation. Its cellular activities are mediated by high affinity interaction with the vitamin D receptor. In brain, autoradiographic, immunohistologic, and messenger RNA expression studies implicate a number ...


    pub_type: 杂志文章


    authors: Langub MC,Herman JP,Malluche HH,Koszewski NJ

    更新日期:2001-01-01 00:00:00

  • An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction.

    abstract::Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the ...


    pub_type: 杂志文章


    authors: Hutch CR,Hillard CJ,Jia C,Hegg CC

    更新日期:2015-08-06 00:00:00

  • Fine structural changes in the superior cervical ganglion of adult rats after long-term administration of baclofen, a GABAB receptor agonist.

    abstract::The aim of the present study was to examine the fine structural changes in the superior cervical ganglion of adult rats following baclofen treatment. On the addition of this GABAB receptor agonist there was a transient increase in the number of coated vesicles and pits in the dendrites of principal sympathetic neurons...


    pub_type: 杂志文章


    authors: Parducz A,Joó F,Siklós L,Wolff JR

    更新日期:1990-01-01 00:00:00

  • High-affinity and selectivity of neosurugatoxin for the inhibition of 22Na influx via nicotinic receptor-ion channel in cultured bovine adrenal medullary cells: comparative study with histrionicotoxin.

    abstract::In cultured bovine adrenal medullary cells, neosurugatoxin and histrionicotoxin inhibited carbachol-induced influx of 22Na, 45Ca and secretion of catecholamines with IC50 of 27 nM and 3 microM, respectively. The inhibitory effects of neosurugatoxin were reversed by the increased concentrations of carbachol, whereas th...


    pub_type: 杂志文章


    authors: Wada A,Uezono Y,Arita M,Tsuji K,Yanagihara N,Kobayashi H,Izumi F

    更新日期:1989-01-01 00:00:00

  • Neural activation in arousal and reward areas of the brain in day-active and night-active grass rats.

    abstract::In the diurnal unstriped Nile grass rat (Arvicanthis niloticus) access to a running wheel can trigger a shift in active phase preference, with some individuals becoming night-active (NA), while others continue to be day-active (DA). To investigate the contributions of different neural systems to the support of this sh...


    pub_type: 杂志文章


    authors: Castillo-Ruiz A,Nixon JP,Smale L,Nunez AA

    更新日期:2010-01-20 00:00:00

  • Evidence for a periaqueductal gray-nucleus retroambiguus-spinal cord pathway in the rat.

    abstract::The nucleus retroambiguus in the cat has been shown to receive strong projections from the periaqueductal gray and to send fibres to distinct motoneuronal cell groups in brainstem and spinal cord. The nucleus retroambiguus plays a role in the production of vocalization and possibly copulatory (lordosis and mounting) b...


    pub_type: 杂志文章


    authors: Holstege G,Kerstens L,Moes MC,Vanderhorst VG

    更新日期:1997-09-01 00:00:00

  • Unintentional force changes in cyclical tasks performed by an abundant system: Empirical observations and a dynamical model.

    abstract::The study explored unintentional force changes elicited by removing visual feedback during cyclical, two-finger isometric force production tasks. Subjects performed two types of tasks at 1Hz, paced by an auditory metronome. One - Force task - required cyclical changes in total force while maintaining the sharing, defi...


    pub_type: 杂志文章


    authors: Reschechtko S,Hasanbarani F,Akulin VM,Latash ML

    更新日期:2017-05-14 00:00:00

  • Plasticity of the GABA(A) receptor subunit cassette in response to stressors in reactive versus resilient mice.

    abstract::GABA(A) functioning has been implicated in anxiety and depressive disorders. In this regard, we suggested that in addition to analyzing GABA(A) and the subunits that comprise the GABA(A) receptor, it might be profitable to assess the coordinated expression of subunits that comprise the GABA(A) receptor cassette. We de...


    pub_type: 杂志文章


    authors: Poulter MO,Du L,Zhurov V,Merali Z,Anisman H

    更新日期:2010-02-17 00:00:00

  • GABA transport and neuroinflammation are coupled in multiple sclerosis: regulation of the GABA transporter-2 by ganaxolone.

    abstract::Interactions between neurotransmitters and the immune system represent new prospects for understanding neuroinflammation and associated neurological disease. GABA is the chief inhibitory neurotransmitter but its actions on immune pathways in the brain are unclear. In the present study, we investigated GABAergic transp...


    pub_type: 杂志文章


    authors: Paul AM,Branton WG,Walsh JG,Polyak MJ,Lu JQ,Baker GB,Power C

    更新日期:2014-07-25 00:00:00

  • Adenosine and the homeostatic control of sleep: effects of A1 receptor blockade in the perifornical lateral hypothalamus on sleep-wakefulness.

    abstract::The orexinergic neurons of the lateral hypothalamus (LH) are critical for wakefulness [McCarley RW (2007) Neurobiology of REM and NREM sleep. Sleep Med 8:302-330]. Recent evidence suggests that adenosine (AD), a homeostatic sleep factor, may act via A1 receptor (A1R) to control orexinergic activity and regulate sleep-...


    pub_type: 杂志文章


    authors: Thakkar MM,Engemann SC,Walsh KM,Sahota PK

    更新日期:2008-06-02 00:00:00

  • Input-output relations in the entorhinal cortex-dentate-hippocampal system: evidence for a non-linear transfer of signals.

    abstract::In the current study we analyzed the input-output relations in the entorhinal-dentate-hippocampal system, a major network involved in long-term memory. In anesthetized guinea pigs, the system was driven by activation of perforant path neurons in the entorhinal cortex (ENT), via presubicular fibers directly stimulated ...


    pub_type: 杂志文章


    authors: Bartesaghi R,Migliore M,Gessi T

    更新日期:2006-09-29 00:00:00

  • Protein kinase C activation by phorbol esters induces chromaffin cell cortical filamentous actin disassembly and increases the initial rate of exocytosis in response to nicotinic receptor stimulation.

    abstract::Nicotinic stimulation and high K+ depolarization of bovine chromaffin cells cause disassembly of cortical filamentous actin networks. Previous work from our laboratory has demonstrated that disassembly of actin filaments is Ca(2+)-dependent, precedes exocytosis and occurs in cortical areas of low cytoplasmic viscosity...


    pub_type: 杂志文章


    authors: Vitale ML,Rodríguez Del Castillo A,Trifaró JM

    更新日期:1992-11-01 00:00:00

  • Transient lesion-induced increase of basic fibroblast growth factor and its receptor in layer VIb (subplate cells) of the adult rat cerebral cortex.

    abstract::Basic fibroblast growth factor is a potent trophic factor with a wide spectrum of activity at various stages of neuronal development. In our studies on the effects of select lesions on the expression of growth factors, we observed that neurons of layer VIb of the rat cerebral cortex developed immunoreactivity for basi...


    pub_type: 杂志文章


    authors: Gómez-Pinilla F,Cotman CW

    更新日期:1992-08-01 00:00:00

  • Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus.

    abstract::The suprachiasmatic nucleus (SCN) is a circadian oscillator and biological clock. Cell-to-cell communication is important for synchronization among SCN neuronal oscillators and the great majority of SCN neurons use GABA as a neurotransmitter, the principal inhibitory neurotransmitter in the adult CNS. Acting via the i...


    pub_type: 杂志文章


    authors: Belenky MA,Sollars PJ,Mount DB,Alper SL,Yarom Y,Pickard GE

    更新日期:2010-02-17 00:00:00

  • Fast, synchronous neurotransmitter release: Past, present and future.

    abstract::This mini-review starts with a summary of the crucial contributions Ricardo Miledi made to our understanding of how the action potential triggers fast, synchronous transmitter release. It then transitions to the discovery of synaptotagmin and its role as the exocytotic Ca2+ sensor at nerve terminals. The final section...


    pub_type: 杂志文章,评审


    authors: Gundersen CB

    更新日期:2020-07-15 00:00:00