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Neural receptor dysfunction

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https://www.readbyqxmd.com/read/28912019/a-nigro-vagal-pathway-controls-gastric-motility-and-is-affected-in-a-rat-model-of-parkinsonism
#1
Laura Anselmi, Luca Toti, Cecilia Bove, Jessica Hampton, R Alberto Travagli
BACKGROUND & AIMS: In most patients with Parkinson's disease, gastrointestinal (GI) dysfunctions, such as gastroparesis and constipation, are prodromal to the cardinal motor symptoms of the disease. Sporadic Parkinson's disease has been proposed to develop following ingestion of neurotoxicants that affect the brain-gut axis via the vagus nerve, and then travel to higher centers compromising the substantia nigra pars compacta (SNpc), and, later, the cerebral cortex. We aimed to identify the pathway that connects the brainstem vagal nuclei and the SNpc, and to determine whether this pathway is compromised in a rat model of Parkinsonism...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28901728/gaba-type-a-receptor-trafficking-and-the-architecture-of-synaptic-inhibition
#2
REVIEW
Joshua M Lorenz-Guertin, Tija C Jacob
Ubiquitous expression of GABA type A receptors (GABAA R) in the central nervous system establishes their central role in coordinating most aspects of neural function and development. Dysregulation of GABAergic neurotransmission manifests in a number of human health disorders and conditions that in certain cases can be alleviated by drugs targeting these receptors. Precise changes in the quantity or activity of GABAA Rs localized at the cell surface and at GABAergic postsynaptic sites directly impact the strength of inhibition...
September 13, 2017: Developmental Neurobiology
https://www.readbyqxmd.com/read/28900300/rogdi-defines-gabaergic-control-of-a-wake-promoting-dopaminergic-pathway-to-sustain-sleep-in-drosophila
#3
Minjong Kim, Donghoon Jang, Eunseok Yoo, Yangkyun Oh, Jun Young Sonn, Jongbin Lee, Yoonhee Ki, Hyo Jin Son, Onyou Hwang, Changwook Lee, Chunghun Lim, Joonho Choe
Kohlschutter-Tönz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by supporting a specific subset of gamma-aminobutyric acid (GABA) transmission. Rogdi mutant flies displayed insomnia-like behaviors accompanied by sleep fragmentation and delay in sleep initiation...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890075/down-regulation-of-dorsal-striatal-%C3%AE-camkii-causes-striatum-related-cognitive-and-synaptic-disorders
#4
Qi Wang, Pengcheng Yin, Bin Yu, Zheng Zhao, Gal Richter-Levin, Lu Yu, Xiaohua Cao
Alpha calcium/calmodulin dependent protein kinase II (αCaMKII) is a serine/threonine protein kinase which is expressed abundantly in dorsal striatum and is highly involved in the corticostriatal synaptic plasticity. Nevertheless, it currently remains unclear whether and how αCaMKII plays a in the striatum-related neural disorders. To address the above issue, lentivirus-mediated short hairpin RNA (shRNA) was used to silence the expression of αCaMKII gene in the dorsal striatum of mice. As a consequence of down-regulation of dorsal striatal αCaMKII expression, we observed defective motor skill learning in accelerating rotarod and response learning in water cross maze...
September 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28864976/overview-of-human-oxytocin-research
#5
Keith M Kendrick, Adam J Guastella, Benjamin Becker
Social dysfunction is a core symptom of many psychiatric disorders and current medications have little or no remedial effects on this. Following on from extensive studies on animal models demonstrating that the neuropeptide oxytocin plays an important role in social recognition and bonding, human-based research has explored its therapeutic potential for social dysfunction in psychiatric disorders. Here we outline the historical background of this human-based research and some of the current methodological challenges it is facing...
September 2, 2017: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/28864239/network-oscillatory-activity-driven-by-context-memory-processing-is-differently-regulated-by-glutamatergic-and-cholinergic-neurotransmission
#6
Adam M P Miller, Brendan J Frick, David M Smith, Jelena Radulovic, Kevin A Corcoran
Memory retrieval requires coordinated intra- and inter-regional activity in networks of brain structures. Dysfunction of these networks and memory impairment are seen in many psychiatric disorders, but relatively little is known about how memory retrieval and memory failure are represented at the level of local and regional oscillatory activity. To address this question, we measured local field potentials (LFPs) from mice as they explored a novel context, retrieved memories for contextual fear conditioning, and after administration of two amnestic agents: the NMDA receptor antagonist MK-801 and muscarinic acetylcholine receptor antagonist scopolamine (SCOP)...
August 30, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28855798/abnormalities-of-dopamine-d3-receptor-signaling-in-the-diseased-brain
#7
REVIEW
G Aleph Prieto
Dopamine D3 receptors (D3R) modulate neuronal activity in several brain regions including cortex, striatum, cerebellum, and hippocampus. A growing body of evidence suggests that aberrant D3R signaling contributes to multiple brain diseases, such as Parkinson's disease, essential tremor, schizophrenia, and addiction. In line with these findings, D3R has emerged as a potential target in the treatment of neurological disorders. However, the mechanisms underlying neuronal D3R signaling are poorly understood, either in healthy or diseased brain...
2017: Journal of Central Nervous System Disease
https://www.readbyqxmd.com/read/28852393/adult-neural-stem-cell-dysfunction-in-the-subventricular-zone-of-the-lateral-ventricle-leads-to-diabetic-olfactory-defects
#8
Yu-Hong Jing, Chu-Chu Qi, Li Yuan, Xiang-Wen Liu, Li-Ping Gao, Jie Yin
Sensitive smell discrimination is based on structural plasticity of the olfactory bulb, which depends on migration and integration of newborn neurons from the subventricular zone. In this study, we examined the relationship between neural stem cell status in the subventricular zone and olfactory function in rats with diabetes mellitus. Streptozotocin was injected through the femoral vein to induce type 1 diabetes mellitus in Sprague-Dawley rats. Two months after injection, olfactory sensitivity was decreased in diabetic rats...
July 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28822836/fty720-fingolimod-an-oral-s1pr-modulator-mitigates-radiation-induced-cognitive-deficits
#9
Alexander M Stessin, Matei A Banu, Mariano Guardia Clausi, Nicholas Berry, John A Boockvar, Samuel Ryu
PURPOSE: This study evaluates FTY720/Fingolimod, modulator of sphingosine-1-phosphate (S1P) receptor, as a potential mitigator of radiation-induced neurocognitive dysfunction. METHODS AND MATERIALS: To study radiation-induced neurocognitive deficits, 6 week-old C57/Bl/6J mice received 0 or 7Gy cranial irradiation and were treated with FTY720 or vehicle for seven weeks. Fear conditioning and Morris water maze were then employed to test learning and memory. Immunohistochemical staining for neural progenitor cells (NPCs) and mature neurons was used to assess changes in hippocampal neurogenesis...
August 16, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28821999/developmental-neurotoxicity-of-the-hippocampus-following-in-utero-exposure-to-methylmercury-impairment-in-cell-signaling
#10
Luana Heimfarth, Jeferson Delgado, Moara Rodrigues Mignori, Daniel Pens Gelain, José Cláudio Fonseca Moreira, Regina Pessoa-Pureur
In this study, we assessed some hippocampal signaling cascades and behavioral impairments in 30-day-old rat pups prenatally exposed to methylmercury (MeHg). Pregnant rats were exposed to 1.0 or 2.0 mg/kg MeHg by gavage in alternated days from gestational day 5 until parturition. We found increased anxiety-like and decreased exploration behavior evaluated by open field test and deficit of both short- and long-term memories by novel object recognition task, respectively, in MeHg-treated pups. Downregulated PI3K/Akt/mTOR pathway and activated/hypophosphorylated (Ser9) GSK3β in MeHg-treated pups could be upstream of hyperphosphorylated Tau (Ser396) destabilizing microtubules and contributing to neural dysfunction in the hippocampus of these rats...
August 18, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28770113/potential-roles-of-exosomal-micrornas-as-diagnostic-biomarkers-and-therapeutic-application-in-alzheimer-s-disease
#11
REVIEW
Jian-Jiao Chen, Bin Zhao, Jie Zhao, Shao Li
Exosomes are bilipid layer-enclosed vesicles derived from endosomes and are released from neural cells. They contain a diversity of proteins, mRNAs, and microRNAs (miRNAs) that are delivered to neighboring cells and/or are transported to distant sites. miRNAs released from exosomes appear to be associated with multiple neurodegenerative conditions linking to Alzheimer's disease (AD) which is marked by hyperphosphorylated tau proteins and accumulation of Aβ plaques. Exciting findings reveal that miRNAs released from exosomes modulate the expression and function of amyloid precursor proteins (APP) and tau proteins...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28768995/physiological-roles-of-carnitine-organic-cation-transporter-octn1-slc22a4-in-neural-cells
#12
Noritaka Nakamichi, Yukio Kato
Dysfunction in neurotransmission mediated by neurotransmitters causes various neurological disorders. Therefore, receptors and reuptake transporters of neurotransmitters have been focused on as a therapeutic target in neurological disorders. These membrane proteins have high affinity for a specific neurotransmitter and are highly expressed on synaptic membranes. In contrast, xenobiotic transporters have relatively lower affinity for neurotransmitters but widely recognize various organic cations and/or anions and are also expressed in brain neurons...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28760865/dystroglycan-maintains-inner-limiting-membrane-integrity-to-coordinate-retinal-development
#13
Reena Clements, Rolf Turk, Kevin P Campbell, Kevin M Wright
Proper neural circuit formation requires the precise regulation of neuronal migration, axon guidance, and dendritic arborization. Mutations affecting the function of the transmembrane glycoprotein dystroglycan cause a form of congenital muscular dystrophy that is frequently associated with neurodevelopmental abnormalities. Despite its importance in brain development, the role of dystroglycan in regulating retinal development remains poorly understood. Using a mouse model of dystroglycanopathy (ISPD(L79*) ) and conditional dystroglycan mutants of both sexes, we show that dystroglycan is critical for the proper migration, axon guidance, and dendritic stratification of neurons in the inner retina...
August 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28751664/afferent-specific-role-of-nmda-receptors-for-the-circuit-integration-of-hippocampal-neurogliaform-cells
#14
R Chittajallu, J C Wester, M T Craig, E Barksdale, X Q Yuan, G Akgül, C Fang, D Collins, S Hunt, K A Pelkey, C J McBain
Appropriate integration of GABAergic interneurons into nascent cortical circuits is critical for ensuring normal information processing within the brain. Network and cognitive deficits associated with neurological disorders, such as schizophrenia, that result from NMDA receptor-hypofunction have been mainly attributed to dysfunction of parvalbumin-expressing interneurons that paradoxically express low levels of synaptic NMDA receptors. Here, we reveal that throughout postnatal development, thalamic, and entorhinal cortical inputs onto hippocampal neurogliaform cells are characterized by a large NMDA receptor-mediated component...
July 28, 2017: Nature Communications
https://www.readbyqxmd.com/read/28738878/tlr4-response-mediates-ethanol-induced-neurodevelopment-alterations-in-a-model-of-fetal-alcohol-spectrum-disorders
#15
María Pascual, Jorge Montesinos, Sandra Montagud-Romero, Jerónimo Forteza, Marta Rodríguez-Arias, José Miñarro, Consuelo Guerri
BACKGROUND: Inflammation during brain development participates in the pathogenesis of early brain injury and cognitive dysfunctions. Prenatal ethanol exposure affects the developing brain and causes neural impairment, cognitive and behavioral effects, collectively known as fetal alcohol spectrum disorders (FASD). Our previous studies demonstrate that ethanol activates the innate immune response and TLR4 receptor and causes neuroinflammation, brain damage, and cognitive defects in the developmental brain stage of adolescents...
July 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28729914/effects-of-mtor-on-neurological-deficits-after-transient-global-ischemia
#16
Jihong Xing, Jian Lu
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase and activation of its signal pathway plays an important role in regulating protein growth and synthesis as well as cell proliferation and survival. In the present study, we examined the contribution of mTOR and its downstream products to brain injuries and neurological deficiencies after cardiac arrest (CA) induced-transient global ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation (CPR) in rats. Our results showed that expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in CA rats compared to their controls...
2017: Translational Neuroscience
https://www.readbyqxmd.com/read/28729439/striatal-gpr88-modulates-foraging-efficiency
#17
Aundrea Rainwater, Elisenda Sanz, Richard D Palmiter, Albert Quintana
The striatum is anatomically and behaviorally implicated in behaviors that promote efficient foraging. To investigate this function, we studied instrumental choice behavior in mice lacking GPR88, a striatum-enriched orphan G-protein-coupled receptor that modulates striatal medium spiny neuron excitability. Our results reveal that hungry mice lacking GPR88 (KO mice) were slow to acquire food-reinforced lever press but could lever press similar to controls on a progressive ratio schedule. Both WT and KO mice discriminated between reward and no-reward levers; however, KO mice failed to discriminate based on relative quantity-reward (1 vs 3 food pellets) or effort (3 vs 9 lever presses)...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28729065/neural-circuits-for-social-cognition-implications-for-autism
#18
REVIEW
Marta Fernández, Irene Mollinedo-Gajate, Olga Peñagarikano
Social neuroscience, the study of the neurobiological basis of social behavior, has become a major area of current research in behavioral neuroscience and psychiatry, since many psychiatric disorders are characterized by social deficits. Social behavior refers to the behavioral response with regard to socially relevant information, and requires the perception and integration of social cues through a complex cognition process (i.e. social cognition) that involves attention, memory, motivation and emotion. Neurobiological and molecular mechanisms underlying social behavior are highly conserved across species, and inter- and intra-specific variability observed in social behavior can be explained to large extent by differential activity of this conserved neural network...
July 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28727688/diazepam-actions-in-the-vta-enhance-social-dominance-and-mitochondrial-function-in-the-nucleus-accumbens-by-activation-of-dopamine-d1-receptors
#19
M A van der Kooij, F Hollis, L Lozano, I Zalachoras, S Abad, O Zanoletti, J Grosse, I Guillot de Suduiraut, C Canto, C Sandi
Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28716328/new-frontiers-of-basic-science-research-in-neurogenic-lower-urinary-tract%C3%A2-dysfunction
#20
REVIEW
Minoru Miyazato, Katsumi Kadekawa, Takeya Kitta, Naoki Wada, Nobutaka Shimizu, William C de Groat, Lori A Birder, Anthony J Kanai, Seiichi Saito, Naoki Yoshimura
The lower urinary tract's main functions are storage and elimination. The micturition reflex pathway is modulated by the spinobulbospinal reflex pathway as well as higher brain centers involved in the voluntary micturition control. Micturition is sensitive to numerous injuries, resulting in various types of dysfunction. Animal studies indicate that lower urinary tract dysfunction partly depends on plasticity of the neural pathways. Reflex plasticity is associated with changes in ion channels, receptors, and numerous mediators...
August 2017: Urologic Clinics of North America
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