Skip to main content
Top
Published in: Metabolic Brain Disease 1/2014

01-03-2014 | Original Paper

The effects of hyperammonemia in learning and brain metabolic activity

Authors: Natalia Arias, Camino Fidalgo, Vicente Felipo, Jorge L. Arias

Published in: Metabolic Brain Disease | Issue 1/2014

Login to get access

Abstract

Ammonia is thought to be central in the development of hepatic encephalopathy. However, the specific relation of ammonia with brain energy depletions and learning has not been studied. Our work attempts to reproduce an increase in rat cerebral ammonia level, study the hyperamonemic animals’ performance of two learning tasks, an allocentric (ALLO) and a cue guided (CG) task, and elucidate the contribution of hyperammonemia to the differential energy requirements of the brain limbic system regions involved in these tasks. To assess these goals, four groups of animals were used: a control (CHA) CG group (n = 10), a CHA ALLO group (n = 9), a hyperammonemia (HA) CG group (n = 7), and HA ALLO group (n = 8). Oxidative metabolism of the target brain regions were assessed by histochemical labelling of cytochrome oxidase (C.O.). The behavioural results revealed that the hyperammonemic rats were not able to reach the behavioural criterion in either of the two tasks, in contrast to the CHA groups. The metabolic brain consumption revealed increased C.O. activity in the anterodorsal thalamus when comparing the HA ALLO group with the CHA ALLO group. Significant differences between animals trained in the CG task were observed in the prelimbic, infralimbic, parietal, entorhinal and perirhinal cortices, the anterolateral and anteromedial striatum, and the basolateral and central amygdala. Our findings may provide fresh insights to reveal how the differential damage to the brain limbic structures involved in these tasks differs according to the degree of task difficulty.
Literature
go back to reference Abe H, Ishida Y, Nonaka H, Iwasaki T (2009) Functional difference between rat perirhinal cortex and hippocampus in object and place discrimination tasks. Behav Brain Res 197:388–397PubMedCrossRef Abe H, Ishida Y, Nonaka H, Iwasaki T (2009) Functional difference between rat perirhinal cortex and hippocampus in object and place discrimination tasks. Behav Brain Res 197:388–397PubMedCrossRef
go back to reference Aggleton JP, Vann SD, Oswald CJ, Good M (2000) Identifying cortical inputs to the rat hippocampus that subserve allocentric spatial processes: A simple problem with a complex answer. Hippocampus 10:466–474PubMedCrossRef Aggleton JP, Vann SD, Oswald CJ, Good M (2000) Identifying cortical inputs to the rat hippocampus that subserve allocentric spatial processes: A simple problem with a complex answer. Hippocampus 10:466–474PubMedCrossRef
go back to reference Aguilar MA, Miñarro J, Felipo V (2000) Chronic moderate hyperammonemia impairs active and passive avoidance behavior and conditional discrimination learning in rats. Exp Neurol 161:704–713PubMedCrossRef Aguilar MA, Miñarro J, Felipo V (2000) Chronic moderate hyperammonemia impairs active and passive avoidance behavior and conditional discrimination learning in rats. Exp Neurol 161:704–713PubMedCrossRef
go back to reference Arias JL, Aller MA, Sánchez-Patan F, Arias J (2006) The inflammatory bases of hepatic encephalopathy. Eur J Gastroenterol Hepatol 18:1297–1310PubMedCrossRef Arias JL, Aller MA, Sánchez-Patan F, Arias J (2006) The inflammatory bases of hepatic encephalopathy. Eur J Gastroenterol Hepatol 18:1297–1310PubMedCrossRef
go back to reference Arias N, Álvarez C, Conejo N, González-Pardo H, Arias JL (2010) Estrous cycle and sex as regulating factors of baseline brain oxidative metabolism and behavior. Revista Iberoamericana de Psicología y Salud 1:3–16 Arias N, Álvarez C, Conejo N, González-Pardo H, Arias JL (2010) Estrous cycle and sex as regulating factors of baseline brain oxidative metabolism and behavior. Revista Iberoamericana de Psicología y Salud 1:3–16
go back to reference Arias N, Méndez M, Arias J, Arias JL (2012) Brain metabolism and spatial memory are affected by portal hypertension. Metab Brain Dis 27:183–191PubMedCrossRef Arias N, Méndez M, Arias J, Arias JL (2012) Brain metabolism and spatial memory are affected by portal hypertension. Metab Brain Dis 27:183–191PubMedCrossRef
go back to reference Arias N, Méndez M, Fidalgo C, Aller MA, Arias J, Arias JL (2013) Mapping metabolic brain activity in three models of hepatic encephalopathy. Int J Hypertens 390872 Arias N, Méndez M, Fidalgo C, Aller MA, Arias J, Arias JL (2013) Mapping metabolic brain activity in three models of hepatic encephalopathy. Int J Hypertens 390872
go back to reference Azorín I, Miñana MD, Felipo V, Grisolía S (1989) A simple animal model of hyperammonemia. Hepatology 10:311–314PubMedCrossRef Azorín I, Miñana MD, Felipo V, Grisolía S (1989) A simple animal model of hyperammonemia. Hepatology 10:311–314PubMedCrossRef
go back to reference Bernabeu R, Schmitz P, Faillace MP, Izquierdo I, Medina JH (1996) Hippocampal cGMP and cAMP are differentially involved in memory processing of inhibitory avoidance learning. Neuroreport 7:585–588PubMedCrossRef Bernabeu R, Schmitz P, Faillace MP, Izquierdo I, Medina JH (1996) Hippocampal cGMP and cAMP are differentially involved in memory processing of inhibitory avoidance learning. Neuroreport 7:585–588PubMedCrossRef
go back to reference Bernabeu R, Schroder N, Quevedo J, Cammarota M, Izquierdo I, Medina JH (1997) Further evidence for the involvement of a Hippocampal cGMP/cGMP-dependent protein kinase cascade in memory consolidation. Neuroreport 8:2221–2224PubMedCrossRef Bernabeu R, Schroder N, Quevedo J, Cammarota M, Izquierdo I, Medina JH (1997) Further evidence for the involvement of a Hippocampal cGMP/cGMP-dependent protein kinase cascade in memory consolidation. Neuroreport 8:2221–2224PubMedCrossRef
go back to reference Boulton CL, Southam E, Garthwaite J (1995) Nitric oxide-dependent long-term Potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase. Neuroscience 69:699–703PubMedCrossRef Boulton CL, Southam E, Garthwaite J (1995) Nitric oxide-dependent long-term Potentiation is blocked by a specific inhibitor of soluble guanylyl cyclase. Neuroscience 69:699–703PubMedCrossRef
go back to reference Burns LH, Annett L, Kelley AE, Everitt BJ, Robbins TW (1996) Effects of lesions to amygdala, ventral subiculum, medial prefrontal cortex, and nucleus accumbens on the reaction to novelty: Implication for limbic-striatal interactions. Behav Neurosci 110:60–73PubMedCrossRef Burns LH, Annett L, Kelley AE, Everitt BJ, Robbins TW (1996) Effects of lesions to amygdala, ventral subiculum, medial prefrontal cortex, and nucleus accumbens on the reaction to novelty: Implication for limbic-striatal interactions. Behav Neurosci 110:60–73PubMedCrossRef
go back to reference Butterworth RF (1991) Pathophysiology of hepatic encephalopathy: The ammonia hypothesis revisited. In: Bengtsson F, Jeppsson B, Aamdal T, Vistrup H (eds) Progress in hepatic encephalopathy and metabolic nitrogen exchange. CRC Press, Boca Raton, pp 9–24 Butterworth RF (1991) Pathophysiology of hepatic encephalopathy: The ammonia hypothesis revisited. In: Bengtsson F, Jeppsson B, Aamdal T, Vistrup H (eds) Progress in hepatic encephalopathy and metabolic nitrogen exchange. CRC Press, Boca Raton, pp 9–24
go back to reference Butterworth RF (2003) Hepatic encephalopathy. Alcohol Res Health 27:240–246PubMed Butterworth RF (2003) Hepatic encephalopathy. Alcohol Res Health 27:240–246PubMed
go back to reference Calton JL, Turner CS, Cyrenne DL, Lee BR, Taube JS (2008) Landmark control and updating of self-movement cues are largely maintained in head direction cells after lesions of the posterior parietal cortex. Behav Neurosci 122:827–840PubMedCentralPubMedCrossRef Calton JL, Turner CS, Cyrenne DL, Lee BR, Taube JS (2008) Landmark control and updating of self-movement cues are largely maintained in head direction cells after lesions of the posterior parietal cortex. Behav Neurosci 122:827–840PubMedCentralPubMedCrossRef
go back to reference Conejo NM, González-Pardo H, González-Lima F, Arias JL (2010) Spatial learning of the water maze: Progression of brain circuits mapped with cytochrome oxidase histochemistry. Neurobiol Learn and Mem 93:362–371CrossRef Conejo NM, González-Pardo H, González-Lima F, Arias JL (2010) Spatial learning of the water maze: Progression of brain circuits mapped with cytochrome oxidase histochemistry. Neurobiol Learn and Mem 93:362–371CrossRef
go back to reference Cooper AJ, Lai JC (1987) Cerebral ammonia metabolism in normal and hyperammonemic rats. Neurochem Pathol 6:67–95PubMedCrossRef Cooper AJ, Lai JC (1987) Cerebral ammonia metabolism in normal and hyperammonemic rats. Neurochem Pathol 6:67–95PubMedCrossRef
go back to reference Cooper AJ, Plum F (1987) Biochemistry and physiology of brain ammonia. Physiol Rev 67:440–519PubMed Cooper AJ, Plum F (1987) Biochemistry and physiology of brain ammonia. Physiol Rev 67:440–519PubMed
go back to reference Corbalán R, Chatauret N, Behrends S, Butterworth RF, Felipo V (2002) Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients. Hepatology 36:1155–1162PubMedCrossRef Corbalán R, Chatauret N, Behrends S, Butterworth RF, Felipo V (2002) Region selective alterations of soluble guanylate cyclase content and modulation in brain of cirrhotic patients. Hepatology 36:1155–1162PubMedCrossRef
go back to reference de Bruin JP, Moita MP, de Brabander HM, Joosten RN (2001) Place and response learning of rats in a Morris water maze: Differential effects of fimbria fornix and medial prefrontal cortex lesions. Neurobiol Learn Mem 75:164–178PubMedCrossRef de Bruin JP, Moita MP, de Brabander HM, Joosten RN (2001) Place and response learning of rats in a Morris water maze: Differential effects of fimbria fornix and medial prefrontal cortex lesions. Neurobiol Learn Mem 75:164–178PubMedCrossRef
go back to reference Delatour B, Gisquet-Verrier P (2000) Functional role of rat prelimbic-infralimbic cortices in spatial memory: Evidence for their involvement in attention and behavioural flexibility. Behav Brain Res 109:113–128PubMedCrossRef Delatour B, Gisquet-Verrier P (2000) Functional role of rat prelimbic-infralimbic cortices in spatial memory: Evidence for their involvement in attention and behavioural flexibility. Behav Brain Res 109:113–128PubMedCrossRef
go back to reference Dougherty KA, Islam T, Johnston D (2012) Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral hippocampus. J Physiol 590:5707–5722PubMedCrossRef Dougherty KA, Islam T, Johnston D (2012) Intrinsic excitability of CA1 pyramidal neurones from the rat dorsal and ventral hippocampus. J Physiol 590:5707–5722PubMedCrossRef
go back to reference Erceg S, Monfort P, Hernández-Viadel M, Rodrigo R, Montoliu C, Felipo V (2005) Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology 41:299–306PubMedCrossRef Erceg S, Monfort P, Hernández-Viadel M, Rodrigo R, Montoliu C, Felipo V (2005) Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology 41:299–306PubMedCrossRef
go back to reference Felipo V (2013) Hepatic encephalopathy: Effects of liver failure on brain function. Nat Rev Neurosci 14:851–858PubMedCrossRef Felipo V (2013) Hepatic encephalopathy: Effects of liver failure on brain function. Nat Rev Neurosci 14:851–858PubMedCrossRef
go back to reference Galani R, Obis S, Coutureau E, Jarrard L, Cassel JC (2002) A comparison of the effects of fimbria-fornix, Hippocampal, or entorhinal cortex lesions on spatial reference and working memory in rats: Short versus long postsurgical recovery period. Neurobiol Learn Mem 77:1–16PubMedCrossRef Galani R, Obis S, Coutureau E, Jarrard L, Cassel JC (2002) A comparison of the effects of fimbria-fornix, Hippocampal, or entorhinal cortex lesions on spatial reference and working memory in rats: Short versus long postsurgical recovery period. Neurobiol Learn Mem 77:1–16PubMedCrossRef
go back to reference Glenn MJ, Nesbitt C, Mumby DG (2003) Perirhinal cortex lesions produce variable patterns of retrograde amnesia in rats. Behav Brain Res 141:183–193PubMedCrossRef Glenn MJ, Nesbitt C, Mumby DG (2003) Perirhinal cortex lesions produce variable patterns of retrograde amnesia in rats. Behav Brain Res 141:183–193PubMedCrossRef
go back to reference González-Lima F, Cada A (1994) Cytochrome oxidase activity in the auditory system of the mouse: A qualitative and quantitative histochemical study. Neuroscience 63:559–578PubMedCrossRef González-Lima F, Cada A (1994) Cytochrome oxidase activity in the auditory system of the mouse: A qualitative and quantitative histochemical study. Neuroscience 63:559–578PubMedCrossRef
go back to reference Groenewegen HJ, Berendse HW, Wolters JG, Lohman AH (1990) The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: Evidence for a parallel organization. Prog Brain Res 85:95–116PubMedCrossRef Groenewegen HJ, Berendse HW, Wolters JG, Lohman AH (1990) The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: Evidence for a parallel organization. Prog Brain Res 85:95–116PubMedCrossRef
go back to reference Hawkins RA, Mans AM (1989) Brain energy metabolism in hepatic encephalopathy. In: Boulton AA, Baker GB, Butterworth RF (eds) Hepatic encephalopathy. Pathophysiology and treatment. Humana Press, Clifton, pp 159–176CrossRef Hawkins RA, Mans AM (1989) Brain energy metabolism in hepatic encephalopathy. In: Boulton AA, Baker GB, Butterworth RF (eds) Hepatic encephalopathy. Pathophysiology and treatment. Humana Press, Clifton, pp 159–176CrossRef
go back to reference Hermenegildo C, Montoliu C, Llansola M, Muñoz MD, Gaztelu JM, Miñana MD, Felipo V (1998) Chronic hyperammonemia impairs glutamate-nitric oxide-cyclic GMP pathway in cerebellar neurons in culture and in the rat in vivo. Eur J Neurosci 10:3201–3209PubMedCrossRef Hermenegildo C, Montoliu C, Llansola M, Muñoz MD, Gaztelu JM, Miñana MD, Felipo V (1998) Chronic hyperammonemia impairs glutamate-nitric oxide-cyclic GMP pathway in cerebellar neurons in culture and in the rat in vivo. Eur J Neurosci 10:3201–3209PubMedCrossRef
go back to reference Hoover WB, Vertes RP (2007) Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 212:149–179PubMedCrossRef Hoover WB, Vertes RP (2007) Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat. Brain Struct Funct 212:149–179PubMedCrossRef
go back to reference Hunsaker MR, Fieldste PM, Rosenberg JS, Kesner RP (2008) Dissociating the roles of dorsal and ventral CA1 for the temporal processing of spatial locations, visual objects, and odors. Behav Neurosci 122:643–650PubMedCrossRef Hunsaker MR, Fieldste PM, Rosenberg JS, Kesner RP (2008) Dissociating the roles of dorsal and ventral CA1 for the temporal processing of spatial locations, visual objects, and odors. Behav Neurosci 122:643–650PubMedCrossRef
go back to reference Ishikawa A, Nakamura S (2006) Ventral Hippocampal neurons project axons simultaneously to the medial prefrontal cortex and amygdala in the rat. J Neurophysiol 96:2134–2138PubMedCrossRef Ishikawa A, Nakamura S (2006) Ventral Hippocampal neurons project axons simultaneously to the medial prefrontal cortex and amygdala in the rat. J Neurophysiol 96:2134–2138PubMedCrossRef
go back to reference Jessy J, Mans AM, DeJoseph MR, Hawkins RA (1990) Hyperammonaemia causes many of the changes found after portacaval shunting. Biochem J 272:311–317PubMed Jessy J, Mans AM, DeJoseph MR, Hawkins RA (1990) Hyperammonaemia causes many of the changes found after portacaval shunting. Biochem J 272:311–317PubMed
go back to reference Jones BJ, Roberts DJ (1968) The quantitative measurement of motor incoordination in naïve mice using an accelerating rotarod. J Pharm Pharmacol 20:302–304PubMedCrossRef Jones BJ, Roberts DJ (1968) The quantitative measurement of motor incoordination in naïve mice using an accelerating rotarod. J Pharm Pharmacol 20:302–304PubMedCrossRef
go back to reference Jover R, Madaria E, Felipo V, Rodrigo R, Candela A, Compañ A (2005) Animal models in the study of episodic hepatic encephalopathy in cirrhosis. Metab Brain Dis 20:399–408PubMedCrossRef Jover R, Madaria E, Felipo V, Rodrigo R, Candela A, Compañ A (2005) Animal models in the study of episodic hepatic encephalopathy in cirrhosis. Metab Brain Dis 20:399–408PubMedCrossRef
go back to reference Kealy J, Commins S (2011) The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function. Prog Neurobiol 93:522–548PubMedCrossRef Kealy J, Commins S (2011) The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function. Prog Neurobiol 93:522–548PubMedCrossRef
go back to reference Kesner RP (1990) Memory for frequency in rats: Role of the hippocampus and medial prefrontal cortex. Behav Neural Biol 53:402–410PubMedCrossRef Kesner RP (1990) Memory for frequency in rats: Role of the hippocampus and medial prefrontal cortex. Behav Neural Biol 53:402–410PubMedCrossRef
go back to reference Kolb B, Whishaw IQ (2003) Fundamentals of human neuropsychology. Worth Publishers, New York Kolb B, Whishaw IQ (2003) Fundamentals of human neuropsychology. Worth Publishers, New York
go back to reference Llansola M, Hernandez-Viadel M, Erceg S, Montoliu C, Felipo V (2009) Increasing the function of the glutamate-nitric oxide-cyclic guanosine monophosphate pathway increases the ability to learn a Y-maze task. J Neurosci Res 87:2351–2355PubMedCrossRef Llansola M, Hernandez-Viadel M, Erceg S, Montoliu C, Felipo V (2009) Increasing the function of the glutamate-nitric oxide-cyclic guanosine monophosphate pathway increases the ability to learn a Y-maze task. J Neurosci Res 87:2351–2355PubMedCrossRef
go back to reference Long JM, Kesner RP (1996) The effects of dorsal versus ventral Hippocampal, total Hippocampal, and parietal cortex lesions on memory for allocentric distance in rats. Behav Neurosci 110:922–932PubMedCrossRef Long JM, Kesner RP (1996) The effects of dorsal versus ventral Hippocampal, total Hippocampal, and parietal cortex lesions on memory for allocentric distance in rats. Behav Neurosci 110:922–932PubMedCrossRef
go back to reference McDonald RJ, White NM (1994) Parallel information processing in the water maze: Evidence for independent memory systems involving dorsal striatum and hippocampus. Behav Neural Biol 61:260–270PubMedCrossRef McDonald RJ, White NM (1994) Parallel information processing in the water maze: Evidence for independent memory systems involving dorsal striatum and hippocampus. Behav Neural Biol 61:260–270PubMedCrossRef
go back to reference Méndez M, Méndez-López M, López L, Aller MA, Arias J, Arias JL (2011) Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior. J Clin Neurosci 18:690–694PubMedCrossRef Méndez M, Méndez-López M, López L, Aller MA, Arias J, Arias JL (2011) Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior. J Clin Neurosci 18:690–694PubMedCrossRef
go back to reference Mizumori SJ, Puryear CB, Martig AK (2009) Basal ganglia contributions to adaptive navigation. Behav Brain Res 199:32–42PubMedCrossRef Mizumori SJ, Puryear CB, Martig AK (2009) Basal ganglia contributions to adaptive navigation. Behav Brain Res 199:32–42PubMedCrossRef
go back to reference Murthy CR, Rama Rao KV, Bai G, Norenberg MD (2001) Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res 66:282–288PubMedCrossRef Murthy CR, Rama Rao KV, Bai G, Norenberg MD (2001) Ammonia-induced production of free radicals in primary cultures of rat astrocytes. J Neurosci Res 66:282–288PubMedCrossRef
go back to reference Norenberg MD, Huo Z, Neary JT, Roig-Cantesano A (1997) The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission. Glia 21:124–133PubMedCrossRef Norenberg MD, Huo Z, Neary JT, Roig-Cantesano A (1997) The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: Relation to energy metabolism and glutamatergic neurotransmission. Glia 21:124–133PubMedCrossRef
go back to reference Paxinos G, Watson CH (2005) The rat brain in Stereotaxic Coordinates—the new coronal set 5th ed. Elsevier Academic Press. Paxinos G, Watson CH (2005) The rat brain in Stereotaxic Coordinates—the new coronal set 5th ed. Elsevier Academic Press.
go back to reference Raabe WA (1989) Neuropathology of ammonia intoxication. In (RF Butterworth and G Pomier Layrargues, eds.) Hepatic encephalopathy: Pathophysiology and Treatment, Humana Press, Clifton, NJ. Raabe WA (1989) Neuropathology of ammonia intoxication. In (RF Butterworth and G Pomier Layrargues, eds.) Hepatic encephalopathy: Pathophysiology and Treatment, Humana Press, Clifton, NJ.
go back to reference Rao KV, Norenberg MD (2001) Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia. Metab Brain Dis 16:67–78PubMedCrossRef Rao KV, Norenberg MD (2001) Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia. Metab Brain Dis 16:67–78PubMedCrossRef
go back to reference Rodrigo R, Erceg S, Rodriguez-Diaz J, Saez-Valero J, Piedrafita B, Suarez I, Felipo V (2007) Glutamate-induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure. J Neurochem 102:51–64PubMedCrossRef Rodrigo R, Erceg S, Rodriguez-Diaz J, Saez-Valero J, Piedrafita B, Suarez I, Felipo V (2007) Glutamate-induced activation of nitric oxide synthase is impaired in cerebral cortex in vivo in rats with chronic liver failure. J Neurochem 102:51–64PubMedCrossRef
go back to reference Rodrigo R, Felipo V (2006) Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved. Neurochem Int 48:472–477PubMedCrossRef Rodrigo R, Felipo V (2006) Brain regional alterations in the modulation of the glutamate-nitric oxide-cGMP pathway in liver cirrhosis. Role of hyperammonemia and cell types involved. Neurochem Int 48:472–477PubMedCrossRef
go back to reference Rogers JL, Kesner RP (2006) Lesions of the dorsal hippocampus or parietal cortex differentially affect spatial information processing. Behav Neurosci 120:852–860PubMedCrossRef Rogers JL, Kesner RP (2006) Lesions of the dorsal hippocampus or parietal cortex differentially affect spatial information processing. Behav Neurosci 120:852–860PubMedCrossRef
go back to reference Rutten K, Vente JD, Sik A, Ittersum MM, Prickaerts J, Blokland A (2005) The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in Hippocampal slices. Behav Brain Res 164:11–16PubMedCrossRef Rutten K, Vente JD, Sik A, Ittersum MM, Prickaerts J, Blokland A (2005) The selective PDE5 inhibitor, sildenafil, improves object memory in Swiss mice and increases cGMP levels in Hippocampal slices. Behav Brain Res 164:11–16PubMedCrossRef
go back to reference Save E, Poucet B (2000) Involvement of the hippocampus and associative parietal cortex in the use of proximal and distal landmarks for navigation. Behav Brain Res 109:195–206PubMedCrossRef Save E, Poucet B (2000) Involvement of the hippocampus and associative parietal cortex in the use of proximal and distal landmarks for navigation. Behav Brain Res 109:195–206PubMedCrossRef
go back to reference Shawcross DL, Wright G, Olde Damink SW, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138PubMedCrossRef Shawcross DL, Wright G, Olde Damink SW, Jalan R (2007) Role of ammonia and inflammation in minimal hepatic encephalopathy. Metab Brain Dis 22:125–138PubMedCrossRef
go back to reference Smith S, Dringenberg HC, Bennett BM, Thatcher GR, Reynolds JN (2000) A novel nitrate ester reverses the cognitive impairment caused by scopolamine in the Morris water maze. Neuroreport 11:3883–3886PubMedCrossRef Smith S, Dringenberg HC, Bennett BM, Thatcher GR, Reynolds JN (2000) A novel nitrate ester reverses the cognitive impairment caused by scopolamine in the Morris water maze. Neuroreport 11:3883–3886PubMedCrossRef
go back to reference Stewart VC, Sharpe MA, Clark JB, Heales SJ (2000) Astrocyte-derived nitric oxide causes both reversible and irreversible damage to the neuronal mitochondrial respiratory chain. J Neurochem 75:694–700PubMedCrossRef Stewart VC, Sharpe MA, Clark JB, Heales SJ (2000) Astrocyte-derived nitric oxide causes both reversible and irreversible damage to the neuronal mitochondrial respiratory chain. J Neurochem 75:694–700PubMedCrossRef
go back to reference Sutherland RJ, Hoesing JM (1993) Posterior cingulate cortex and spatial memory: A microlimnology analysis. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhauser, Boston Sutherland RJ, Hoesing JM (1993) Posterior cingulate cortex and spatial memory: A microlimnology analysis. In: Vogt BA, Gabriel M (eds) Neurobiology of cingulate cortex and limbic thalamus. Birkhauser, Boston
go back to reference Wang V, Saab S (2003) Ammonia levels and the severity of hepatic encephalopathy. Am J Med 114:237–238PubMedCrossRef Wang V, Saab S (2003) Ammonia levels and the severity of hepatic encephalopathy. Am J Med 114:237–238PubMedCrossRef
go back to reference Weissenborn K, Heidenreich S, Giewekemeyer K, Rückert N, Hecker H (2003) Memory function in early hepatic encephalopathy. J Hepatol 39:320–325PubMedCrossRef Weissenborn K, Heidenreich S, Giewekemeyer K, Rückert N, Hecker H (2003) Memory function in early hepatic encephalopathy. J Hepatol 39:320–325PubMedCrossRef
go back to reference Wiig KA, Bilkey DK (1994) The effects of perirhinal cortical lesions on spatial reference memory in the rat. Behav Brain Res 63:101–109PubMedCrossRef Wiig KA, Bilkey DK (1994) The effects of perirhinal cortical lesions on spatial reference memory in the rat. Behav Brain Res 63:101–109PubMedCrossRef
go back to reference Wolff M, Gibb SJ, Cassel JC, Dalrymple-Alford JC (2008) Anterior but not intralaminar thalamic nuclei support allocentric spatial memory. Neurobiol Learn Mem 90:71–80PubMedCrossRef Wolff M, Gibb SJ, Cassel JC, Dalrymple-Alford JC (2008) Anterior but not intralaminar thalamic nuclei support allocentric spatial memory. Neurobiol Learn Mem 90:71–80PubMedCrossRef
Metadata
Title
The effects of hyperammonemia in learning and brain metabolic activity
Authors
Natalia Arias
Camino Fidalgo
Vicente Felipo
Jorge L. Arias
Publication date
01-03-2014
Publisher
Springer US
Published in
Metabolic Brain Disease / Issue 1/2014
Print ISSN: 0885-7490
Electronic ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-013-9477-0

Other articles of this Issue 1/2014

Metabolic Brain Disease 1/2014 Go to the issue