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












  • Frequency selectivity and dopamine-dependence of plasticity at glutamatergic synapses in the subthalamic nucleus.

    abstract::In Parkinson's disease, subthalamic nucleus (STN) neurons burst fire with increased periodicity and synchrony. This may entail abnormal release of glutamate, the major source of which in STN is cortical afferents. Indeed, the cortico-subthalamic pathway is implicated in the emergence of excessive oscillations, which a...


    pub_type: 杂志文章


    authors: Yamawaki N,Magill PJ,Woodhall GL,Hall SD,Stanford IM

    更新日期:2012-02-17 00:00:00

  • Whisker stimulation metabolically activates thalamus following cortical transplantation but not following cortical ablation.

    abstract::Local cerebral glucose utilization was assessed during whisker stimulation by 2-deoxyglucose autoradiography. Whisker stimulation increased local cerebral glucose utilization in brainstem, thalamus and whisker sensory cortex in normal rats. Whereas whisker stimulation increased glucose metabolism in brainstem, whisker...


    pub_type: 杂志文章


    authors: Ciricillo SP,Hill MP,Gonzalez MF,Smalley S,Morton MT,Sharp FR

    更新日期:1994-04-01 00:00:00

  • Enkephalin-like immunoreactivity within the telencephalon of the reptile Caiman crocodilus.

    abstract::Immunohistochemical methods were used to characterize the distribution of staining for leucine enkephalin-like and methionine enkephalin-like immunoreactivities in the telencephalon of Caiman crocodilus. Very similar distributions of both leucine enkephalin-like and methionine enkephalin-like immunoreactivity were obs...


    pub_type: 杂志文章


    authors: Brauth SE

    更新日期:1984-02-01 00:00:00

  • Changes in response properties of rostral ventromedial medulla neurons during prolonged inflammation: modulation by neurokinin-1 receptors.

    abstract::Activation of neurokinin-1 (NK-1) receptors in the rostral ventromedial medulla (RVM) can facilitate pain transmission in conditions such as inflammation, and thereby contribute to hyperalgesia. Since blockade of NK-1 receptors in the RVM can attenuate hyperalgesia produced by prolonged inflammation, we examined the r...


    pub_type: 杂志文章


    authors: Khasabov SG,Brink TS,Schupp M,Noack J,Simone DA

    更新日期:2012-11-08 00:00:00

  • Amphetamine-induced increase in motor activity is correlated with higher firing rates of non-dopamine neurons in substantia nigra and ventral tegmental area.

    abstract::The responses of non-dopamine neurons in substantia nigra and ventral tegmental area to systemic amphetamine were investigated in the behaving rat chronically implanted with multiple fine-wire electrodes. The neurons were identified with electrophysiological criteria requiring that the signals be of biphasic shape, sh...


    pub_type: 杂志文章


    authors: Olds ME

    更新日期:1988-02-01 00:00:00

  • Brain-derived neurotrophic factor promotes axonal regeneration and long-term survival of adult rat spinal motoneurons in vivo.

    abstract::This study shows that in adult rat spinal motoneurons brain-derived neurotrophic factor exerts a neuroprotective effect which extends several weeks beyond the duration of treatment. In addition, brain-derived neurotrophic factor strongly enhances regeneration of avulsed motor axons across the border between the centra...


    pub_type: 杂志文章


    authors: Novikov L,Novikova L,Kellerth JO

    更新日期:1997-08-01 00:00:00

  • GABA mechanisms and sleep.

    abstract::GABA is the main inhibitory neurotransmitter of the CNS. It is well established that activation of GABA(A) receptors favors sleep. Three generations of hypnotics are based on these GABA(A) receptor-mediated inhibitory processes. The first and second generation of hypnotics (barbiturates and benzodiazepines respectivel...


    pub_type: 杂志文章,评审


    authors: Gottesmann C

    更新日期:2002-01-01 00:00:00

  • Environmental enrichment differentially modifies specific components of sensory-evoked activity in rat barrel cortex as revealed by simultaneous electrophysiological recordings and optical imaging in vivo.

    abstract::Environmental enrichment of laboratory animals leads to multi-faceted changes to physiology, health and disease prognosis. An important and under-appreciated factor in enhancing cognition through environmental manipulation may be improved basic sensory function. Previous studies have highlighted changes in cortical se...


    pub_type: 杂志文章


    authors: Devonshire IM,Dommett EJ,Grandy TH,Halliday AC,Greenfield SA

    更新日期:2010-10-13 00:00:00

  • Deregulation of the hypoxia inducible factor-1α pathway in monocytes from sporadic amyotrophic lateral sclerosis patients.

    abstract::The clinical course of the degenerative motor neuron disorder amyotrophic lateral sclerosis (ALS) is closely related to hypoxia. The normal response to hypoxia involves two pathways in particular: the hypoxia inducible factor 1α (HIF-1α) pathway (which notably controls the synthesis of vascular endothelial growth fact...


    pub_type: 杂志文章


    authors: Moreau C,Gosset P,Kluza J,Brunaud-Danel V,Lassalle P,Marchetti P,Defebvre L,Destée A,Devos D

    更新日期:2011-01-13 00:00:00

  • Distribution of the messenger RNA for the extracellularly regulated kinases 1, 2 and 3 in rat brain: effects of excitotoxic hippocampal lesions.

    abstract::Neurofibrillary tangles in Alzheimer's disease are composed of hyperphosphorylated forms of the microtubule-associated protein tau. Based on biochemical criteria, several enzymes have emerged as potential tau protein kinases, including the extracellularly regulated kinases 1, 2 and 3. In situ hybridization was used to...


    pub_type: 杂志文章


    authors: Hollister RD,Page KJ,Hyman BT

    更新日期:1997-08-01 00:00:00

  • Long-term induction of Fos-related antigen-2 after methamphetamine-, methylenedioxymethamphetamine-, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine- and trimethyltin-induced brain injury.

    abstract::A long-term induction of Fos-related antigens has been shown in neurons after brain injury, suggesting that Fos-related antigens are involved in enhancing the transcription of genes related to the process of regeneration and repair. In the present study, we report that levels of Fos-related antigen-2 are elevated in s...


    pub_type: 杂志文章


    authors: Pennypacker KR,Yang X,Gordon MN,Benkovic S,Miller D,O'Callaghan JP

    更新日期:2000-01-01 00:00:00

  • Neurotrophin potentiation of iron-induced spinal cord injury.

    abstract::Previous studies have shown that pretreatment with neurotrophins can potentiate the vulnerability of cultured neurons to excitotoxic and free radical-induced necrosis, in contrast to their well known neuroprotective effects against apoptosis. Here we tested the hypothesis that this unexpected injury-potentiating effec...


    pub_type: 杂志文章


    authors: Mcdonald JW,Stefovska VG,Liu XZ,Shin H,Liu S,Choi DW

    更新日期:2002-01-01 00:00:00

  • Spinal Circuits Mediate a Stretch Reflex Between the Upper Limbs in Humans.

    abstract::Inter-limb reflexes play an important role in coordinating behaviors involving different limbs. Previous studies have demonstrated that human elbow muscles express an inter-limb stretch reflex at long-latency (50-100 ms), a timing consistent with a trans-cortical linkage. Here we probe for inter-limb stretch reflexes ...


    pub_type: 杂志文章


    authors: Muraoka T,Kurtzer I

    更新日期:2020-04-01 00:00:00

  • Screening for Efficacious Anticonvulsants and Neuroprotectants in Delayed Treatment Models of Organophosphate-induced Status Epilepticus.

    abstract::Organophosphorus (OP) compounds are deadly chemicals that exert their intoxicating effects through the irreversible inhibition of acetylcholinesterase (AChE). In addition to an excess of peripheral ailments, OP intoxication induces status epilepticus (SE) which if left untreated may lead to permanent brain damage or d...


    pub_type: 杂志文章


    authors: Barker BS,Spampanato J,McCarren HS,Smolik M,Jackson CE,Hornung EN,Yeung DT,Dudek FE,McDonough JH

    更新日期:2020-01-15 00:00:00

  • Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function.

    abstract::We have shown that transgenic transient axonal glycoprotein (TAG)/F3 mice, in which the mouse axonal glycoprotein F3/contactin was misexpressed from a regulatory region of the gene encoding the transient axonal glycoprotein TAG-1, exhibit a transient disruption of cerebellar granule and Purkinje cell development [Deve...


    pub_type: 杂志文章


    authors: Coluccia A,Tattoli M,Bizzoca A,Arbia S,Lorusso L,De Benedictis L,Buttiglione M,Cuomo V,Furley A,Gennarini G,Cagiano R

    更新日期:2004-01-01 00:00:00

  • Arginine vasopressin regulated ASCT1 expression in astrocytes from stroke-prone spontaneously hypertensive rats and congenic SHRpch1_18 rats.

    abstract::In stroke-prone spontaneously hypertensive rats (SHRSP/Izm), ischemia induces swelling of astrocytes, a process that subsequently leads to neuronal death. Following ischemic insult, arginine vasopressin (AVP) can induce edema and l-serine released by astrocytes supports the survival of neuronal cells. The purpose of t...


    pub_type: 杂志文章


    authors: Yamagata K,Yamamoto M,Kawakami K,Ohara H,Nabika T

    更新日期:2014-05-16 00:00:00

  • Acidic FGF promotes neurite outgrowth of cortical neurons and improves neuroprotective effect in a cerebral ischemic rat model.

    abstract::Acidic fibroblast growth factor (aFGF) is a neurotrophic factor which is a powerful neuroprotective and neuroregenerative factor of the nervous system. Prior study had shown that levels of FGFs significantly increase following ischemic injury, reflecting a physiological protection mechanism. However, few reports demon...


    pub_type: 杂志文章


    authors: Tsai MJ,Tsai SK,Huang MC,Liou DY,Huang SL,Hsieh WH,Huang WC,Huang SS,Cheng H

    更新日期:2015-10-01 00:00:00

  • Bitter Taste Responses of Gustducin-positive Taste Cells in Mouse Fungiform and Circumvallate Papillae.

    abstract::Bitter taste serves as an important signal for potentially poisonous compounds in foods to avoid their ingestion. Thousands of compounds are estimated to taste bitter and presumed to activate taste receptor cells expressing bitter taste receptors (Tas2rs) and coupled transduction components including gustducin, phosph...


    pub_type: 杂志文章


    authors: Yoshida R,Takai S,Sanematsu K,Margolskee RF,Shigemura N,Ninomiya Y

    更新日期:2018-01-15 00:00:00

  • Influence of mitochondrial enzyme deficiency on adult neurogenesis in mouse models of neurodegenerative diseases.

    abstract::Mitochondrial defects including reduction of a key mitochondrial tricarboxylic acid cycle enzyme alpha-ketoglutarate-dehydrogenase complex (KGDHC) are characteristic of many neurodegenerative diseases. KGDHC consists of alpha-ketoglutarate dehydrogenase, dihydrolipoyl succinyltransferase (E2k), and dihydrolipoamide de...


    pub_type: 杂志文章


    authors: Calingasan NY,Ho DJ,Wille EJ,Campagna MV,Ruan J,Dumont M,Yang L,Shi Q,Gibson GE,Beal MF

    更新日期:2008-06-02 00:00:00

  • Different populations of prostaglandin EP3 receptor-expressing preoptic neurons project to two fever-mediating sympathoexcitatory brain regions.

    abstract::The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidu...


    pub_type: 杂志文章


    authors: Nakamura Y,Nakamura K,Morrison SF

    更新日期:2009-06-30 00:00:00

  • Transmembrane agrin regulates dendritic filopodia and synapse formation in mature hippocampal neuron cultures.

    abstract::The transmembrane isoform of agrin (Tm-agrin) is the predominant form expressed in the brain but its putative roles in brain development are not well understood. Recent reports have implicated Tm-agrin in the formation and stabilization of filopodia on neurites of immature central and peripheral neurons in culture. In...


    pub_type: 杂志文章


    authors: McCroskery S,Bailey A,Lin L,Daniels MP

    更新日期:2009-09-29 00:00:00

  • Inositol trisphosphate and cyclic adenosine diphosphate-ribose increase quantal transmitter release at frog motor nerve terminals: possible involvement of smooth endoplasmic reticulum.

    abstract::The release of chemical transmitter from nerve terminals is critically dependent on a transient increase in intracellular Ca2+. The increase in Ca2+ may be due to influx of Ca2+ from the extracellular fluid or release of Ca2+ from intracellular stores such as mitochondria. Whether Ca2+ utilized in transmitter release ...


    pub_type: 杂志文章


    authors: Brailoiu E,Miyamoto MD

    更新日期:2000-01-01 00:00:00

  • Involvement of protein kinase C and nitric oxide in the modulation by insulin-like growth factor-I of glutamate-induced GABA release in the cerebellum.

    abstract::Insulin-like growth factor-I elicits a long-term depression of the glutamate-induced GABA release in the adult rat cerebellum that lasts at least several hours. We studied whether protein kinase C and nitric oxide may be involved in this effect of insulin-like growth factor-I on GABA release since both signalling path...


    pub_type: 杂志文章


    authors: Castro-Alamancos MA,Arevalo MA,Torres-Aleman I

    更新日期:1996-02-01 00:00:00

  • Regional differences in desensitization of c-Fos expression following repeated self-stimulation of the medial forebrain bundle in the rat.

    abstract::The acute self-stimulation of the medial forebrain bundle was reported to induce the expression of c-Fos, the protein product of c-fos, an immediate early gene, in the central nervous system. In the present study, we examined regional changes in c-Fos expression in several reward-related areas of rat brain in response...


    pub_type: 杂志文章


    authors: Nakahara D,Ishida Y,Nakamura M,Kuwahara I,Todaka K,Nishimori T

    更新日期:1999-03-01 00:00:00

  • The visceral sector of the thalamic reticular nucleus in the rat.

    abstract::Visceral sensory perception is subjected to modulation by attention or distraction, like other sensory systems. The thalamic reticular nucleus is a key region in selective attention, effecting a change in the mode of thalamocortical transmission. Each major thalamocortical system is connected with a particular sector ...


    pub_type: 杂志文章


    authors: Stehberg J,Acuña-Goycolea C,Ceric F,Torrealba F

    更新日期:2001-01-01 00:00:00

  • Central serotonin depletion modulates the behavioural, endocrine and physiological responses to repeated social stress and subsequent c-fos expression in the brains of male rats.

    abstract::Intraspecific confrontation has been used to study effect of depleting central serotonin on the adaptation of male rats to repeated social stress (social defeat). Four groups of adult male rats were used (serotonin depletion/sham: stressed; serotonin depletion/sham: non-stressed). Central serotonin was reduced (by 59-...


    pub_type: 杂志文章


    authors: Chung KK,Martinez M,Herbert J

    更新日期:1999-01-01 00:00:00

  • Hypertonicity increases NO production to modulate the firing rate of magnocellular neurons of the supraoptic nucleus of rats.

    abstract::Increases in plasma osmolality enhance nitric oxide (NO) levels in magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and modulate the secretion of both vasopressin (VP) and oxytocin (OT). In this paper, we describe the effects of hypertonicity on the electrical properties of MNCs by focusing on...


    pub_type: 杂志文章


    authors: da Silva MP,Ventura RR,Varanda WA

    更新日期:2013-10-10 00:00:00

  • Involvement of Rho-kinase in inflammatory and neuropathic pain through phosphorylation of myristoylated alanine-rich C-kinase substrate (MARCKS).

    abstract::Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major in vivo substrate for protein kinase C in the brain and has been implicated in cellular processes associated with cytoskeletal restructuring such as synaptic trafficking and neurotransmitter release. A phosphorylation-site specific antibody against Ser1...


    pub_type: 杂志文章


    authors: Tatsumi S,Mabuchi T,Katano T,Matsumura S,Abe T,Hidaka H,Suzuki M,Sasaki Y,Minami T,Ito S

    更新日期:2005-01-01 00:00:00

  • Midbrain areas required for locomotion initiated by electrical stimulation of the lateral hypothalamus in the anesthetized rat.

    abstract::Locomotor stepping in the Nembutal-anesthetized rat was elicited by electrical stimulation of either of two sites in the right or left posterolateral hypothalamus. Essential midbrain loci were identified by reversibly blocking the elicited locomotion through local injections of the anesthetic procaine (15%, 0.5 microl...


    pub_type: 杂志文章


    authors: Levy DI,Sinnamon HM

    更新日期:1990-01-01 00:00:00

  • Blockade of micro-opioid receptors in the medial thalamus inhibits acquisition, but not expression, of morphine-induced conditioned place preference.

    abstract::The medial thalamus contains abundant mu-opioid receptors and is activated by acute morphine administration. However, the role of the medial thalamus in the rewarding effects of morphine is unclear. The present study examined whether mu-opioid receptors of the medial thalamus influenced the acquisition and expression ...


    pub_type: 杂志文章


    authors: Guo N,Garcia MM,Taylor BK,Zadina JE,Harlan RE

    更新日期:2008-02-19 00:00:00