Elsevier

Neurobiology of Disease

Volume 23, Issue 3, September 2006, Pages 512-521
Neurobiology of Disease

Taurine rescues hippocampal long-term potentiation from ammonia-induced impairment

https://doi.org/10.1016/j.nbd.2006.04.006Get rights and content

Abstract

Hyperammonemia, a major pathophysiological factor in hepatic encephalopathy, impairs long-term potentiation (LTP) of synaptic transmission, a cellular model of learning and memory, in the hippocampus. We have now studied the protective action of taurine on this paradigm by analyzing LTP characteristics in mouse hippocampal slices treated with ammonium chloride (1 mM) in the presence of taurine (1 mM), an ubiquitous osmolyte, antioxidant, and neuromodulator, as well as other substances with such properties. Ammonia-treated slices displayed a significant impairment of LTP maintenance. Taurine and the mitochondrial enhancer l-carnitine, but not the antioxidants (ascorbate, carnosine, and the novel compound GVS-111) or the osmolyte betaine prevented this impairment. The protective effect of taurine was preserved under the blockade of inhibitory GABAA and glycine receptors. It is suggested that taurine may rescue the mechanisms of hippocampal synaptic plasticity by improving mitochondrial function under hyperammonemic conditions.

Introduction

Ammonia, a common intermediate in a variety of metabolic pathways, is neurotoxic when accumulating in excess. Acute and chronic liver failures result in an up to fourfold rise of its concentration in the brain leading to the impairment of cerebral functions progressing from relatively mild cognitive disturbances to stupor and coma (Butterworth, 2002, Haussinger et al., 2002, Albrecht and Jones, 1999, Hazell and Butterworth, 1999). In acute ammonia intoxication, all neurological and neurochemical manifestations are reversed by antagonists of N-methyl-d-aspartate (NMDA) receptors indicating a pivotal role of glutamate excitotoxicity in ammonia-induced brain damage (Kosenko et al., 1994, Vogels et al., 1997, Felipo and Butterworth, 2002).

Moderate chronic hyperammonemia characteristic of hepatic encephalopathy (HE) is associated with a shift in the balance between inhibitory and excitatory neurotransmission towards a net increase of inhibitory neurotransmission, as a consequence of at least two factors (Albrecht and Jones, 1999, Monfort et al., 2002a): (i) an increase in inhibitory GABA-ergic “tone” due to a direct potentiating action of ammonium ions on GABAA receptors (Takahashi et al., 1993), and due to the increased brain levels of positive modulators of GABAA receptors such as pregnenolone-derived neurosteroids and benzodiazepines (Albrecht, 1998); (ii) a functional down-regulation of glutamate receptors and decreased glutamatergic tone, as a consequence of excessive extrasynaptic accumulation of glutamate due to the inactivation of the glutamate transporter GLT-1 in astrocytes (Butterworth, 2001, Chan et al., 2000, Knecht et al., 1997). Signal transduction pathways associated with NMDA receptors are found down-regulated under hyperammonemic conditions (Marcaida et al., 1995).

Glutamate receptors of the NMDA type are critically involved in some forms of synaptic plasticity underlying learning and memory processes (Bliss and Collingridge, 1993). Chronic moderate hyperammonemia impairs behavioral learning (Aguilar et al., 2000) and the expression of NMDA receptor-dependent long-term potentiation (LTP) of synaptic transmission in the hippocampal Schaffer collateral-CA1 pathway (Munoz et al., 2000).

Activation of NMDA receptors under hyperammonemia is accompanied by oxidative stress and overproduction of reactive oxygen and nitrogen species (Kosenko et al., 1997, Kosenko et al., 2003, Norenberg, 2003). Taurine (2-aminoethanesulfonic acid), an ubiquitous endogenous osmolyte, antioxidant, and inhibitory neuromodulator (Huxtable, 1992) protects a variety of tissues from oxidative stress injury (Balkan et al., 2001, Chang et al., 2004, Dawson et al., 2002, Gurer et al., 2001, Obrosova et al., 2001). It also increases cell survival under conditions of oxidative (Hayes et al., 2001, Rivas-Arancibia et al., 2001) and seizure-induced (El Abhar and El Gawad, 2003, Hogema et al., 2001) brain damage, attenuates glutamate excitotoxicity in cell culture models (Boldyrev et al., 1999, Trenkner et al., 1996) and counteracts cell swelling and free radical accumulation under experimental hyperammonemia (Hilgier et al., 2003, Zielinska et al., 2003). We examined now possible protective functions of taurine and other compounds on ammonia-induced impairment of NMDA-dependent hippocampal synaptic plasticity.

Section snippets

Materials and methods

Hippocampal slices were prepared from the brains of male C57Bl/6 mice aged from 10 to 12 weeks. The animals were decapitated, the brains were rapidly removed and placed into ice-cold oxygenated (95%O2, 5%CO2) standard artificial CSF (ACSF), which contained (mM) 124 NaCl, 3.7 KCl, 1.24 NaH2PO4, 1.3 MgSO4, 2 CaCl2, 26 NaHCO3, 10 glucose. The brain was cut to horizontal slices, 400 μm thick, using a Vibroslicer (Campden Instruments). After dissection, the hippocampal slices were maintained at room

Ammonia- induced impairment of LTP in CA1 and its reversal by taurine

In control slices HFS caused robust initial potentiation that considerably decreased during the first 20–30 min and then persisted at a level of about 30% over baseline by the end of observation period (136 ± 4%, n = 22, at 45–60 min post-HFS, pooled control, Fig. 1A). The ability to evoke LTP in hippocampal slices continuously exposed to 1 mM ammonia was significantly reduced: potentiation induced by HFS progressively decreased to 109 ± 4% in slices preincubated with ammonia immediately after

Discussion

Taurine and l-carnitine restore the ammonia-evoked impairment of hippocampal LTP, a cellular model and module of learning and memory (Bliss and Collingridge, 1993). The impairment of LTP demonstrated here is in keeping with previous findings in hippocampal slices from hyperammonemic rats (Munoz et al., 2000) and recent data using acute exposure of rat hippocampal slices to ammonia (Izumi et al., 2005). Taurine is involved in many physiological functions (Huxtable, 1992); among those, regulation

Acknowledgments

This study was supported by grants from the DFG (SFB 575) and RFBR (04-04-49422). We thank T.A. Gudasheva and R.U. Ostrovskaya for GVS-111.

References (81)

  • W. Hilgier et al.

    Taurine prevents ammonia-induced accumulation of cyclic GMP in rat striatum by interaction with GABAA and glycine receptors

    Brain Res.

    (2005)
  • K. Hino et al.

    l-carnitine inhibits hypoglycemia-induced brain damage in the rat

    Brain Res.

    (2005)
  • Y. Izumi et al.

    Ammonia-mediated LTP inhibition: Effects of NMDA receptor antagonists and l-carnitine

    Neurobiol. Dis.

    (2005)
  • O. Kloiber et al.

    Protection against acute hyperammonemia: the role of quaternary amines

    Toxicology

    (1988)
  • K. Knecht et al.

    Decreased glutamate transporter (GLT-1) expression in frontal cortex of rats with acute liver failure

    Neurosci. Lett.

    (1997)
  • E. Kosenko et al.

    Alteration of mitochondrial calcium homeostasis by ammonia-induced activation of NMDA receptors in rat brain in vivo

    Brain Res.

    (2000)
  • E. Kosenko et al.

    Sources of oxygen radicals in brain in acute ammonia intoxication in vivo

    Brain Res.

    (2003)
  • M. Levy et al.

    Mitochondrial regulation of synaptic plasticity in the hippocampus

    J. Biol. Chem.

    (2003)
  • M.D. Norenberg

    Oxidative and nitrosative stress in ammonia neurotoxicity

    Hepatology

    (2003)
  • I.G. Obrosova et al.

    Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy

    Exp. Neurol.

    (2001)
  • M. Palmi et al.

    Potentiation of mitochondrial Ca2+ sequestration by taurine

    Biochem. Pharmacol.

    (1999)
  • A.C. Paula-Lima et al.

    Activation of GABA(A) receptors by taurine and muscimol blocks the neurotoxicity of beta-amyloid in rat hippocampal and cortical neurons

    Neuropharmacology

    (2005)
  • A. Pelsman et al.

    GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons

    Int. J. Dev. Neurosci.

    (2003)
  • M.E. Rice

    Ascorbate regulation and its neuroprotective role in the brain

    Trends Neurosci.

    (2000)
  • K.H. Taber et al.

    Taurine in hippocampus: localization and postsynaptic action

    Brain Res.

    (1986)
  • K. Takahashi et al.

    Ammonia potentiates GABAA response in dissociated rat cortical neurons

    Neurosci. Lett.

    (1993)
  • J.M. Williams et al.

    Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus

    Brain Res. Mol. Brain Res.

    (1998)
  • M. Zielinska et al.

    Excitotoxic mechanism of cell swelling in rat cerebral cortical slices treated acutely with ammonia

    Neurochem. Int.

    (2003)
  • J. Albrecht

    Roles of neuroactive amino acids in ammonia neurotoxicity

    J. Neurosci. Res.

    (1998)
  • J. Albrecht et al.

    The role of inhibitory amino acidergic neurotransmission in hepatic encephalopathy: a critical overview

    Metab. Brain Dis.

    (2002)
  • G. Atmaca

    Antioxidant effects of sulfur-containing amino acids

    Yonsei Med. J.

    (2004)
  • J. Balkan et al.

    Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress

    Hum. Exp. Toxicol.

    (2001)
  • Z.I. Bashir et al.

    Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors

    Nature

    (1993)
  • T.C. Birdsall

    Therapeutic applications of taurine

    Alt. Med. Rev.

    (1998)
  • T.V. Bliss et al.

    A synaptic model of memory: long-term potentiation in the hippocampus

    Nature

    (1993)
  • A.A. Boldyrev et al.

    Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals

    Cell. Mol. Neurobiol.

    (1997)
  • R.F. Butterworth

    Glutamate transporter and receptor function in disorders of ammonia metabolism

    Ment. Retard. Dev. Disabil. Res. Rev.

    (2001)
  • R.F. Butterworth

    Pathophysiology of hepatic encephalopathy: a new look at ammonia

    Metab. Brain Dis.

    (2002)
  • L. Chang et al.

    Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells

    Acta Pharmacol. Sin.

    (2004)
  • S.C. Chattipakorn et al.

    Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices

    J. Neurophysiol.

    (2002)
  • Cited by (49)

    • The nephroprotective properties of taurine in colistin-treated mice is mediated through the regulation of mitochondrial function and mitigation of oxidative stress

      2019, Biomedicine and Pharmacotherapy
      Citation Excerpt :

      It has been found that taurine supplementation enhanced cellular antioxidant capacity, mitigated oxidative stress, and significantly abated biological targets injury induced by a variety of xenobiotics [23–31]. On the other hand, several studies indicated the positive effects of taurine on cellular mitochondria [32–36]. It has been found that taurine boosted mitochondrial antioxidant systems, decreased mitochondria-facilitated ROS formation, and enhanced mitochondrial membrane potential and ATP content [33,34,37,38].

    View all citing articles on Scopus
    1

    On leave from Brain Research Institute, Russian Academy of Medical Sciences, Moscow 105064, Russia.

    View full text