In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1β, NMDA receptors in membrane and working memory in hyperammonemic rats

Cabrera‐Pastor, Andrea; Hernández‐Rabaza, Vicente; Taoro‐González, Lucas; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

doi:10.1016/j.bbi.2016.05.011

Cited by 33 publications

(57 citation statements)

References 46 publications

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“…Extracellular cGMP normalized the surface expression of GluA1 and GluA2 but not those of NR1 and NR2A. These extracellular cGMP‐induced changes were associated with restoration of spatial reference memory but not working memory in hyperammonaemic rats …”

Section: Role Of Peripheral Inflammation Neuroinflammation and Altermentioning

confidence: 90%

“…This was associated with increased membrane expression in the hippocampus of the NR1 and NR2A subunits of NMDA receptors and of the GluA1 subunit of AMPA receptors and with reduced membrane expression of the GluA2 subunit of AMPA receptors. These changes were also associated with impaired spatial reference memory and working memory …”

Section: Role Of Peripheral Inflammation Neuroinflammation and Altermentioning

confidence: 97%

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Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications

et al. 2019

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Several million patients with liver cirrhosis suffer minimal hepatic encephalopathy (MHE), with mild cognitive and coordination impairments that reduce their quality of life and life span. Hyperammonaemia and peripheral inflammation act synergistically to induce these neurological alterations. We propose that MHE appearance is because of the changes in peripheral immune system, which are transmitted to brain, leading to neuroinflammation that alters neurotransmission leading to cognitive and motor alterations. We summarize studies showing that MHE in cirrhotic patients is associated with alterations in the immune system and that patients died with HE show neuroinflammation in cerebellum, with microglial and astrocytic activation and Purkinje cell loss. We also summarize studies in animal models of MHE on the role of peripheral inflammation in neuroinflammation induction, how neuroinflammation alters neurotransmission and how this leads to cognitive and motor alterations. These studies identify therapeutic targets and treatments that improve cognitive and motor function. Rats with MHE show neuroinflammation in hippocampus and altered NMDA and AMPA receptor membrane expression, which impairs spatial learning and memory. Neuroinflammation in cerebellum is associated with altered GABA transporters and extracellular GABA, which impair motor coordination and learning in a Y maze. These alterations are reversed by treatments that reduce peripheral inflammation (anti‐TNFα, ibuprofen), neuroinflammation (sulphoraphane, p38 inhibitors), GABAergic tone (bicuculline, pregnenolone sulphate) or increase extracellular cGMP (sildenafil or cGMP). The mechanisms identified would also occur in other chronic diseases associated with inflammation, aging and some mental and neurodegenerative diseases. Treatments that improve MHE may also be beneficial to treat these pathologies.

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Section: Role Of Peripheral Inflammation Neuroinflammation and Altermentioning

confidence: 90%

Section: Role Of Peripheral Inflammation Neuroinflammation and Altermentioning

confidence: 97%

Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications

et al. 2019

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“…The employed XL BS 3 is an established analytical agent in protein biochemistry . BS 3 is water‐soluble, homo‐bifunctional, non‐cleavable and amine‐reactive making this XL molecule especially suitable to stabilize complex protein structures . The XL‐protein conjugation reaction can be carried out under experimental circumstances that are relatively close to physiological conditions.…”

Section: Introductionmentioning

confidence: 99%

Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle

et al. 2018

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Duchenne muscular dystrophy is a highly progressive muscle wasting disease with a complex pathophysiology that is based on primary abnormalities in the dystrophin gene. In order to study potential changes in the oligomerization of high‐molecular‐mass protein complexes in dystrophic skeletal muscle, chemical crosslinking was combined with mass spectrometric analysis. The biochemical stabilization of protein interactions was carried out with the homo‐bifunctional and amine‐reactive agent bis[sulfosuccinimidyl]suberate, followed by protein shift analysis in one‐dimensional gels. The proteomic approach identified 11 and 15 protein species in wild type versus dystrophic microsomal fractions, respectively, as well as eight common proteins, with an electrophoretic mobility shift to very high molecular mass following chemical crosslinking. In dystrophin‐deficient preparations, several protein species with an increased tendency of oligomerisation were identified as components of the sarcolemma and its associated intra‐ and extracellular structures, as well as mitochondria. This included the sarcolemmal proteins myoferlin and caveolin, the cytoskeletal components vimentin and tubulin, extracellular collagen alpha‐1(XII) and the mitochondrial trifunctional enzyme and oxoglutarate dehydrogenase. These changes are probably related to structural and metabolic adaptations, especially cellular repair processes, which agrees with the increased oligomerisation of myosin‐3, myosin‐9 and actin, and their role in cellular regeneration and structural adjustments in dystrophinopathy.

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“…In hippocampus, IL‐1b or lipopolysaccharide enhances GABAergic neurotransmission by enhancing membrane expression of GABA A receptors . This is prevented by co‐incubation with the IL‐1 receptor antagonist IL‐1Ra .…”

Section: Resultsmentioning

confidence: 99%

“…In hippocampus, IL-1b or lipopolysaccharide enhances GABAergic neurotransmission by enhancing membrane expression of GABA A receptors. [34][35][36] This is prevented by co-incubation with the IL-1 receptor antagonist IL-1Ra. 34 It seems therefore that IL-1b would play a main role in increasing membrane expression of GABA A receptors, but the underlying mechanisms remain unknown.…”

Section: Pcs Rats Show Both Inflammation and Hyperammonemia Ratsmentioning

confidence: 99%

Sildenafil reduces neuroinflammation in cerebellum, restores GABAergic tone, and improves motor in‐coordination in rats with hepatic encephalopathy

et al. 2017

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In vivo administration of extracellular cGMP normalizes TNF-α and membrane expression of AMPA receptors in hippocampus and spatial reference memory but not IL-1β, NMDA receptors in membrane and working memory in hyperammonemic rats

Cited by 33 publications

References 46 publications

Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications

Peripheral inflammation induces neuroinflammation that alters neurotransmission and cognitive and motor function in hepatic encephalopathy: Underlying mechanisms and therapeutic implications

Comparative gel‐based proteomic analysis of chemically crosslinked complexes in dystrophic skeletal muscle

Sildenafil reduces neuroinflammation in cerebellum, restores GABAergic tone, and improves motor in‐coordination in rats with hepatic encephalopathy

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