Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis

Sergeeva, Olga A.; Schulz, Daniela; Doreulee, Nanuli; Ponomarenko, Alexey; Selbach, Oliver; Borsch, Elena; Kircheis, G.; Huston, J.P.; Häussinger, Dieter; Haas, Helmut L.

doi:10.1016/j.neuroscience.2005.05.031

Cited by 41 publications

(23 citation statements)

References 43 publications

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“…One may also speculate that A B C D chronic hyperammonemia from birth in Glul fl/fl × Alb-Cre + mice may trigger so far unknown adaptations that are not present in other experimental settings or in patients with liver failure. However, that chronic hyperammonemia in Glul fl/fl × Alb-Cre + mice does not promote anxious behavior is consistent with findings obtained from bile duct-ligated rats (47) or rats after portocaval anastomosis (50). Interestingly, oxidative stress markers were not elevated in the piriform cortex of liver-specific GS KO mice.…”

Section: Discussionsupporting

confidence: 88%

Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

Qvartskhava

Lang

Görg

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Urea cycle defects and acute or chronic liver failure are linked to systemic hyperammonemia and often result in cerebral dysfunction and encephalopathy. Although an important role of the liver in ammonia metabolism is widely accepted, the role of ammonia metabolizing pathways in the liver for maintenance of whole-body ammonia homeostasis in vivo remains ill-defined. Here, we show by generation of liver-specific Gln synthetase (GS)-deficient mice that GS in the liver is critically involved in systemic ammonia homeostasis in vivo. Hepatic deletion of GS triggered systemic hyperammonemia, which was associated with cerebral oxidative stress as indicated by increased levels of oxidized RNA and enhanced protein Tyr nitration. Liver-specific GS-deficient mice showed increased locomotion, impaired fear memory, and a slightly reduced life span. In conclusion, the present observations highlight the importance of hepatic GS for maintenance of ammonia homeostasis and establish the liver-specific GS KO mouse as a model with which to study effects of chronic hyperammonemia.hepatic encephalopathy | metabolic zonation | oxidative stress | RNA oxidation | glutamine

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Section: Discussionsupporting

confidence: 88%

Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

Qvartskhava

Lang

Görg

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Different positive controls were taken in order to demonstrate that there is no preferential amplification of the ADAR2Sc isoform under our amplification conditions. We found no change in editing of any site of GluR2 and GluR4 or in 5-HT 2C R editing sites in the whole TMN dissected from rats with a portacaval anastomosis (Sergeeva et al 2005b) under conditions where the high ammonium level could interfere with the deamination. All these rats (n = 4) demonstrated a high level of ADAR2Lc splice variant expression, which is an indicator of enhanced ADAR2 enzymatic activity (Fig.…”

Section: Splicing Within the Coding Region Of Adar2mentioning

confidence: 58%

Editing of AMPA and Serotonin 2C Receptors in Individual Central Neurons, Controlling Wakefulness

2007

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(1) Pre-mRNA editing of serotonin 2C (5-HT2c) and glutamate (Glu) receptors (R) influences higher brain functions and pathological states such as epilepsy, amyotrophic lateral sclerosis, and depression. Adenosine deaminases acting on RNA (ADAR1-3) convert adenosine to inosine on synthetic RNAs, analogous to 5-HT2cR and GluR. The order of editing as well as mechanisms controlling editing in native neurons is unknown. (2) With single-cell RT-PCR we investigated the co-expression of ADAR genes with GluR and 5-HT2cR and determined the editing status at known sites in the hypothalamic tuberomamillary nucleus, a major center for wakefulness and arousal. (3) The most frequently expressed enzymes were ADAR1, followed by ADAR2. The Q/R site of GluR2 was always fully edited. Editing at the R/G site in the GluR2 (but not GluR4) subunit was co-ordinated with ADAR expression: maximal editing was found in neurons expressing both ADAR2 splice variants of the deaminase domain and lacking ADAR3. (4) Editing of the 5-HT2cR did not correlate with ADAR expression. The 5-HT2cR mRNA was always edited at A, in the majority of cells at B sites and variably edited at E, C and D sites. A negative correlation was found between editing of C and D sites. The GluR4 R/G site editing was homogeneous within individuals: it was fully edited in all neurons obtained from 12 rats and under-edited in six neurons obtained from three rats. (5) We conclude that GluR2 R/G editing is controlled at the level of ADAR2 and therefore this enzyme may be a target for pharmacotherapy. On the other hand, further factors/enzymes besides ADAR must control or influence 5-HT2cR and GluR pre-mRNA editing in native neurons; our data indicate that these factors vary between individuals and could be predictors of psychiatric disease.

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“…Psychological tests revealed also deficits in learning and memory capacities [8] which may persist after resolution of overt HE [9]. The impairment of locomotor and cognitive functions is also consistently observed in animal models of HE as well as during hyperammonemia without liver dysfunction [10][11][12][13].The striatum is the primary input nucleus of the basal ganglia receiving information from all regions of the cerebral cortex through topographically-organized glutamatergic projections.Information from all regions of the cerebral cortex is integrated by striatal principal neurons, medium size spiny neurons (MSNs) under control of striatal interneurons and dopaminergic input from the substantia nigra. Activity-dependent alterations of synaptic efficacy in the corticostriatal pathway form the basis for motor learning [14][15][16].…”

mentioning

confidence: 99%

“…Impairment of corticostriatal synaptic plasticity was found to accompany alcoholism [27,28] and brain aging [29]. Although changes in the efficiency of corticostriatal input must have a great impact on the function of basal ganglia circuitry modulating motor activity, only a few studies analysed changes in striatal synaptic plasticity in an animal model of HE [13] and hyperammonemia [30].Liver dysfunction and hyperammonemia, the key factor in the pathogenesis of HE [31,32], affect signalling associated with activation of NMDA and mGlu I glutamate receptors [33,34] which are 0003-9861/$ -see front matter Ó …”

mentioning

confidence: 99%

Alterations of corticostriatal plasticity by ammonium and rescue by green tea polyphenols

Chepkova¹,

Sergeeva²,

Haas³

2013

Archives of Biochemistry and Biophysics

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Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis

Cited by 41 publications

References 43 publications

Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

Hyperammonemia in gene-targeted mice lacking functional hepatic glutamine synthetase

Editing of AMPA and Serotonin 2C Receptors in Individual Central Neurons, Controlling Wakefulness

Alterations of corticostriatal plasticity by ammonium and rescue by green tea polyphenols

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