Taurine rescues hippocampal long-term potentiation from ammonia-induced impairment
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)
- et al.
Chronic moderate hyperammonemia impairs active and passive avoidance behavior and conditional discrimination learning in rats
Exp. Neurol.
(2000) - et al.
Hepatic encephalopathy: molecular mechanisms underlying the clinical syndrome
J. Neurol. Sci.
(1999) - et al.
Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity
Cell Calcium
(2003) - et al.
Carnosine and taurine protect rat cerebellar granular cells from free radical damage
Neurosci. Lett.
(1999) - et al.
Effects of ammonia on glutamate transporter (GLAST) protein and mRNA in cultured rat cortical astrocytes
Neurochem. Int.
(2000) - et al.
Taurine activates GABA(A) but not GABA(B) receptors in rat hippocampal CA1 area
Brain Res.
(2000) - et al.
Taurine-induced synaptic potentiation and the late phase of long-term potentiation are related mechanistically
Neuropharmacology
(2003) - et al.
Mitochondrial dysfunction in acute hyperammonemia
Neurochem. Int.
(2002) - et al.
Complexities in the neurotoxic actions of 6-hydroxydopamine in relation to the cytoprotective properties of taurine
Brain Res. Bull.
(2001) - et al.
Taurine reduces ammonia- and N-methyl-d-aspartate-induced accumulation of cyclic GMP and hydroxyl radicals in microdialysates of the rat striatum
Eur. J. Pharmacol.
(2003)
Taurine prevents ammonia-induced accumulation of cyclic GMP in rat striatum by interaction with GABAA and glycine receptors
Brain Res.
l-carnitine inhibits hypoglycemia-induced brain damage in the rat
Brain Res.
Ammonia-mediated LTP inhibition: Effects of NMDA receptor antagonists and l-carnitine
Neurobiol. Dis.
Protection against acute hyperammonemia: the role of quaternary amines
Toxicology
Decreased glutamate transporter (GLT-1) expression in frontal cortex of rats with acute liver failure
Neurosci. Lett.
Alteration of mitochondrial calcium homeostasis by ammonia-induced activation of NMDA receptors in rat brain in vivo
Brain Res.
Sources of oxygen radicals in brain in acute ammonia intoxication in vivo
Brain Res.
Mitochondrial regulation of synaptic plasticity in the hippocampus
J. Biol. Chem.
Oxidative and nitrosative stress in ammonia neurotoxicity
Hepatology
Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy
Exp. Neurol.
Potentiation of mitochondrial Ca2+ sequestration by taurine
Biochem. Pharmacol.
Activation of GABA(A) receptors by taurine and muscimol blocks the neurotoxicity of beta-amyloid in rat hippocampal and cortical neurons
Neuropharmacology
GVS-111 prevents oxidative damage and apoptosis in normal and Down's syndrome human cortical neurons
Int. J. Dev. Neurosci.
Ascorbate regulation and its neuroprotective role in the brain
Trends Neurosci.
Taurine in hippocampus: localization and postsynaptic action
Brain Res.
Ammonia potentiates GABAA response in dissociated rat cortical neurons
Neurosci. Lett.
Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus
Brain Res. Mol. Brain Res.
Excitotoxic mechanism of cell swelling in rat cerebral cortical slices treated acutely with ammonia
Neurochem. Int.
Roles of neuroactive amino acids in ammonia neurotoxicity
J. Neurosci. Res.
The role of inhibitory amino acidergic neurotransmission in hepatic encephalopathy: a critical overview
Metab. Brain Dis.
Antioxidant effects of sulfur-containing amino acids
Yonsei Med. J.
Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress
Hum. Exp. Toxicol.
Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors
Nature
Therapeutic applications of taurine
Alt. Med. Rev.
A synaptic model of memory: long-term potentiation in the hippocampus
Nature
Biochemical and physiological evidence that carnosine is an endogenous neuroprotector against free radicals
Cell. Mol. Neurobiol.
Glutamate transporter and receptor function in disorders of ammonia metabolism
Ment. Retard. Dev. Disabil. Res. Rev.
Pathophysiology of hepatic encephalopathy: a new look at ammonia
Metab. Brain Dis.
Taurine antagonized oxidative stress injury induced by homocysteine in rat vascular smooth muscle cells
Acta Pharmacol. Sin.
Pharmacological characterization of glycine-gated chloride currents recorded in rat hippocampal slices
J. Neurophysiol.
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 PharmacotherapyCitation 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].
- 1
On leave from Brain Research Institute, Russian Academy of Medical Sciences, Moscow 105064, Russia.