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https://www.readbyqxmd.com/read/29913190/neurochemical-changes-underlying-schizophrenia-related-behavior-in-a-modified-forced-swim-test-in-mice
#1
Monika Wożniak, Paulina Cieślik, Marcin Marciniak, Tomasz Lenda, Andrzej Pilc, Joanna M Wieronska
The modified forced swim test (MFST) has excellent predictive validity for investigating the antipsychotic activity of drugs, with particular emphasis on their activity toward negative symptoms of schizophrenia. However, its face and construct validity are less understood. Therefore, in the present study, some biochemical changes within GABAergic and serotonergic neurotransmission that could be related to observed MK-801-induced disturbances and the activity of compounds active at those neurotransmitters were investigated...
June 15, 2018: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/29885525/enhanced-postsynaptic-gaba-b-receptor-signaling-in-adult-spinal-projection-neurons-after-neonatal-injury
#2
Chelsie L Brewer, Mark L Baccei
Clinical and basic science research have revealed persistent effects of early life injury on nociceptive processing and resulting pain sensitivity. While recent work has identified clear deficits in fast GABAA - and glycine receptor-mediated inhibition in the adult spinal dorsal horn after neonatal tissue damage, the effects of early injury on slow, metabotropic inhibition within spinal pain circuits are poorly understood. Here we provide evidence that neonatal surgical incision significantly enhances postsynaptic GABAB receptor signaling within the mature superficial dorsal horn (SDH) in a cell type-dependent manner...
June 6, 2018: Neuroscience
https://www.readbyqxmd.com/read/29883723/nmda-and-gaba-receptor-presence-in-rat-heart-mitochondria
#3
Semen V Nesterov, Yulia A Skorobogatova, Alisa A Panteleeva, Lyubov L Pavlik, Irina B Mikheeva, Lev S Yaguzhinsky, Yaroslav R Nartsissov
The purpose of this study is to demonstrate the presence of three more receptors in mitochondria. Two N-methyl-d-aspartate receptor (NMDAR) subunits (NR1 and NR2B) are found by protein immunoblot and immunogold labeling in mitochondria fraction isolated from rat heart. These data allow supposing NMDAR presence and functioning in the inner mitochondrial membrane. There are no signs of receptor presence obtained in heart tissue lysate, that indicates the receptor localization exactly in mitochondria. The possible receptor functions discussed are its participation in calcium transport and in excitation-metabolism coupling...
June 5, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29881949/ca-2-calmodulin-dependent-protein-kinase-ii-camkii-%C3%AE-dependent-phosphorylation-of-gaba-b1-triggers-lysosomal-degradation-of-gaba-b-receptors-via-mind-bomb-2-mib2-mediated-lys-63-linked-ubiquitination
#4
Khaled Zemoura, Karthik Balakrishnan, Thomas Grampp, Dietmar Benke
The G protein-coupled GABAB receptors, constituted from GABAB1 and GABAB2 subunits, are important regulators of neuronal excitability by mediating long-lasting inhibition. One factor that determines receptor availability and thereby the strength of inhibition is regulated protein degradation. GABAB receptors are constitutively internalized from the plasma membrane and are either recycled to the cell surface or degraded in lysosomes. Lys-63-linked ubiquitination mediated by the E3 ligase Mind bomb-2 (MIB2) is the signal that sorts GABAB receptors to lysosomes...
June 7, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29875265/activating-transcription-factor-4-atf4-regulates-neuronal-activity-by-controlling-gaba-b-r-trafficking
#5
Carlo Corona, Silvia Pasini, Jin Liu, Fatou Amar, Lloyd A Greene, Michael L Shelanski
Activating Transcription Factor 4 (ATF4) has been postulated as a key regulator of learning and memory. We previously reported that specific hippocampal ATF4 down-regulation causes deficits in synaptic plasticity and memory and reduction of glutamatergic functionality. Here we extend our studies to address ATF4's role in neuronal excitability. We find that long-term ATF4 knockdown in cultured rat hippocampal neurons significantly increases the frequency of spontaneous action potentials. This effect is associated with decreased functionality of metabotropic GABAB receptors (GABAB Rs)...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29869166/metabolism-of-amino-acid-neurotransmitters-the-synaptic-disorder-underlying-inherited-metabolic-diseases
#6
Stefan Kölker
Amino acids are involved in various metabolic pathways and some of them also act as neurotransmitters. Since biosynthesis of L-glutamate and γ-aminobutyric acid (GABA) requires 2-oxoglutarate while 3-phosphoglycerate is the precursor of L-glycine and D-serine, evolutionary selection of these amino acid neurotransmitters might have been driven by their capacity to provide important information about the glycolytic pathway and Krebs cycle. Synthesis and recycling of amino acid neurotransmitters as well as composition and function of their receptors are often compromised in inherited metabolic diseases...
June 4, 2018: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/29859979/effects-of-low-doses-of-ketamine-on-pyramidal-neurons-in-rat-prefrontal-cortex
#7
Guofang Shen, Feng Han, Wei-Xing Shi
Indirect evidence suggests that low doses of ketamine disinhibit (excite) pyramidal neurons in the prefrontal cortex (PFC). In this study, we directly examined the effect of ketamine on PFC pyramidal neurons using simultaneous single-cell and local-field-potential (LFP) recording in chloral hydrate-anesthetized rats. In all animals studied, PFC LFPs showed oscillations (0.3-1.5 Hz) between the active UP state and the relatively quiescent DOWN state, and pyramidal neurons fired preferentially during the UP state...
May 31, 2018: Neuroscience
https://www.readbyqxmd.com/read/29849055/reduced-gabaergic-cortical-inhibition-in-aging-and-depression
#8
Jennifer I Lissemore, Apoorva Bhandari, Benoit H Mulsant, Eric J Lenze, Charles F Reynolds, Jordan F Karp, Tarek K Rajji, Yoshihiro Noda, Reza Zomorrodi, Etienne Sibille, Zafiris J Daskalakis, Daniel M Blumberger
The neurobiology underlying depression in older adults is less extensively evaluated than in younger adults, despite the putative influence of aging on depression neuropathology. Studies using transcranial magnetic stimulation (TMS), a neurophysiological tool capable of probing inhibitory and excitatory cortical neurotransmission, have identified dysfunctional GABAergic inhibitory activity in younger adults with depression. However, GABAergic and glutamatergic cortical neurotransmission have not yet been studied in late-life depression (LLD)...
May 17, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29792150/synthesis-and-biological-evaluation-of-novel-2-3-disubstituted-benzofuran-analogues-of-gaba-as-neurotropic-agents
#9
Arturo Coaviche-Yoval, Hector Luna, Ricardo Tovar-Miranda, Marvin Antonio Soriano-Ursua, Jose G Trujillo-Ferrara
BACKGROUND: Benzofurans are heterocyclic compounds with neurotropic activity. Some have been developed for the treatment of acute and degenerative neuronal injuries. OBJECTIVE: To evaluate the in silico binding of some promising benzofurans on the GABA receptors, and the in vivo neurotropic activity of benzofuran analogues (BZF 6-10) of gamma-aminobutyric acid (GABA) on a seizure model. METHODS: The ligands with the best physicochemical attributes were docked on two GABA receptors (the alpha-1 subunit of GABAA-R and GBR1 subunit of GABAB-R)...
May 23, 2018: Medicinal Chemistry
https://www.readbyqxmd.com/read/29785777/paradoxical-effect-of-baclofen-on-social-behavior-in-the-fragile-x-syndrome-mouse-model
#10
Shimriet Zeidler, Andreea S Pop, Israa A Jaafar, Helen de Boer, Ronald A M Buijsen, Celine E F de Esch, Ingeborg Nieuwenhuizen-Bakker, Renate K Hukema, Rob Willemsen
INTRODUCTION: Fragile X syndrome (FXS) is a common monogenetic cause of intellectual disability, autism spectrum features, and a broad range of other psychiatric and medical problems. FXS is caused by the lack of the fragile X mental retardation protein (FMRP), a translational regulator of specific mRNAs at the postsynaptic compartment. The absence of FMRP leads to aberrant synaptic plasticity, which is believed to be caused by an imbalance in excitatory and inhibitory network functioning of the synapse...
April 26, 2018: Brain and Behavior
https://www.readbyqxmd.com/read/29779874/a-gabaergic-feedback-shapes-dopaminergic-input-on-the-drosophila-mushroom-body-to-promote-appetitive-long-term-memory
#11
Alice Pavlowsky, Johann Schor, Pierre-Yves Plaçais, Thomas Preat
Memory consolidation is a crucial step for long-term memory (LTM) storage. However, we still lack a clear picture of how memory consolidation is regulated at the neuronal circuit level. Here, we took advantage of the well-described anatomy of the Drosophila olfactory memory center, the mushroom body (MB), to address this question in the context of appetitive LTM. The MB lobes, which are made by the fascicled axons of the MB intrinsic neurons, are organized into discrete anatomical modules, each covered by the terminals of a defined type of dopaminergic neuron (DAN) and the dendrites of a corresponding type of MB output neuron (MBON)...
May 9, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29770121/overexpression-of-thioredoxin-1-blocks-morphine-induced-conditioned-place-preference-through-regulating-the-interaction-of-%C3%AE-aminobutyric-acid-and-dopamine-systems
#12
Xiang Li, Mengbing Huang, Lihua Yang, Ningning Guo, Xiaoyan Yang, Zhimin Zhang, Ming Bai, Lu Ge, Xiaoshuang Zhou, Ye Li, Jie Bai
Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29759132/the-gamma-aminobutyric-acid-b-receptor-in-depression-and-reward
#13
REVIEW
Laura H Jacobson, Styliani Vlachou, David A Slattery, Xia Li, John F Cryan
The metabotropic gamma-aminobutyric acid B (GABAB ) receptor was the first described obligate G protein-coupled receptor heterodimer and continues to set the stage for discoveries in G protein-coupled receptor signaling complexity. In this review, dedicated to the life and work of Athina Markou, we explore the role of GABAB receptors in depression, reward, and the convergence of these domains in anhedonia, a shared symptom of major depressive disorder and withdrawal from drugs of abuse. GABAB receptor expression and function are enhanced by antidepressants and reduced in animal models of depression...
June 1, 2018: Biological Psychiatry
https://www.readbyqxmd.com/read/29746088/structure-activity-studies-reveal-the-molecular-basis-for-gabab-receptor-mediated-inhibition-of-high-voltage-activated-calcium-channels-by-%C3%AE-conotoxin-vc1-1
#14
Mahsa Sadeghi, Bodil B Carstens, Brid P Callaghan, James T Daniel, Han Shen Tae, Tracey O'Donnell, Joel Castro, Stuart M Brierley, David J Adams, David J Craik, Richard J Clark
α-Conotoxins are disulfide-bonded peptides from cone snail venoms and are characterized by their affinity for nicotinic acetylcholine receptors (nAChR). Several α-conotoxins with distinct selectivity for nAChR subtypes have been identified as potent analgesics in animal models of chronic pain. However, a number of α-conotoxins have been shown to inhibit N-type calcium channel currents in rodent dissociated dorsal root ganglion (DRG) neurons via activation of G protein-coupled GABAB receptors (GABABR). Therefore it is unclear whether activation of GABABR or inhibition of α9α10 nAChRs is the analgesic mechanism...
May 10, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29742721/coexistence-of-lambert-eaton-myasthenic-syndrome-and-autoimmune-encephalitis-with-anti-crmp5-cv2-and-anti-gabab-receptor-antibodies-in-small-cell-lung-cancer-a-case-report
#15
Hongfang Li, Aimei Zhang, Yanlei Hao, Hongzhi Guan, Zhanyun Lv
RATIONALE: Autoimmune encephalitis and Lambert-Eaton myasthenic syndrome are classic paraneoplastic neurological conditions common in patients with small cell lung cancer. PATIENT CONCERNS: The patient complained of tiredness, fluctuating recent memory loss, and inability to find his home. His family members reported a change in character, irritability, and paranoia. One month later, the patient had 1 grand mal seizure lasting 5 minutes. DIAGNOSIS: The patient was diagnosed with limbic encephalitis combined with Lambert-Eaton myasthenic syndrome...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29722299/the-adjustment-of-%C3%AE-aminobutyric-acid-a-tonic-subunits-in-huntington-s-disease-from-transcription-to-translation-to-synaptic-levels-into-the-neostriatum
#16
REVIEW
Abraham Rosas-Arellano, Argel Estrada-Mondragón, Carola A Mantellero, Carlos Tejeda-Guzmán, Maite A Castro
γ-Aminobutyric acid (GABA), plays a key role in all stages of life, also is considered the main inhibitory neurotransmitter. GABA activates two kind of membrane receptors known as GABAA and GABAB , the first one is responsible to render tonic inhibition by pentameric receptors containing α4-6, β3, δ, or ρ1-3 subunits, they are located at perisynaptic and/or in extrasynaptic regions. The biophysical properties of GABAA tonic inhibition have been related with cellular protection against excitotoxic injury and cell death in presence of excessive excitation...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29717222/paraneoplastic-limbic-encephalitis-associated-with-lung-cancer
#17
Kaini Shen, Yan Xu, Hongzhi Guan, Wei Zhong, Minjiang Chen, Jing Zhao, Longyun Li, Mengzhao Wang
Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in lung cancer patients. We retrospectively investigated the clinical characteristics, treatment responses, and prognoses in 16 PLE patients who were subsequently diagnosed with lung cancer. Fifteen patients initially presented with disturbance of consciousness, 13 with disorientation, and 12 with seizures. Thirteen patients had autoantibodies, including eight with gamma aminobutyric acid B receptor (GABAB R) antibodies and eight with Hu antibodies...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29704609/complex-learning-induced-modifications-in-synaptic-inhibition-mechanisms-and-functional-significance
#18
REVIEW
Iris Reuveni, Longnian Lin, Edi Barkai
Following training in a difficult olfactory-discrimination (OD) task rats acquire the capability to perform the task easily, with little effort. This new acquired skill, of 'learning how to learn' is termed 'rule learning'. At the single cell level, rule learning in manifested in long-term enhancement of intrinsic neuronal excitability of piriform cortex (PC) pyramidal neurons, and in excitatory synaptic connections between these neuros to maintained cortical stability, such long-lasting increase in excitability must be accompanied by paralleled increase in inhibitory processes that would prevent hyper-excitable activation...
April 25, 2018: Neuroscience
https://www.readbyqxmd.com/read/29703993/cortical-inhibitory-markers-of-lifetime-suicidal-behavior-in-depressed-adolescents
#19
Charles P Lewis, Paul A Nakonezny, Caren J Blacker, Jennifer L Vande Voort, John D Port, Gregory A Worrell, Hang Joon Jo, Zafiris J Daskalakis, Paul E Croarkin
Although suicide is the second-leading cause of death in adolescents and young adults worldwide, little progress has been made in developing reliable biological markers of suicide risk and suicidal behavior. Converging evidence suggests that excitatory and inhibitory cortical processes mediated by the neurotransmitters glutamate and γ-aminobutyric acid (GABA) are dysregulated in suicidal individuals. This study utilized single- and paired-pulse transcranial magnetic stimulation (TMS) to assess excitatory and inhibitory cortical functioning in healthy control adolescents (n = 20), depressed adolescents without any history of suicidal behavior ("Depressed", n = 37), and depressed adolescents with lifetime history of suicidal behavior ("Depressed+SB", n = 17)...
March 14, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29667225/activation-of-central-gaba-b-receptors-offsets-the-cyclosporine-counteraction-of-endotoxic-cardiovascular-outcomes-in-conscious-rats
#20
Marwa Y Sallam, Sahar M El-Gowilly, Abdel-Galil A Abdel-Galil, Mahmoud M El-Mas
We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study, we investigated whether the facilitation of central γ-amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS-CSA interaction was determined in the absence and presence of drugs that activate GABAA or GABAB receptors or elevate synaptic GABA levels in the central nervous system...
April 18, 2018: Fundamental & Clinical Pharmacology
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