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https://www.readbyqxmd.com/read/28344757/leveraging-blood-serotonin-as-an-endophenotype-to-identify-de-novo-and-rare-variants-involved-in-autism
#1
Rui Chen, Lea K Davis, Stephen Guter, Qiang Wei, Suma Jacob, Melissa H Potter, Nancy J Cox, Edwin H Cook, James S Sutcliffe, Bingshan Li
BACKGROUND: Autism spectrum disorder (ASD) is one of the most highly heritable neuropsychiatric disorders, but underlying molecular mechanisms are still unresolved due to extreme locus heterogeneity. Leveraging meaningful endophenotypes or biomarkers may be an effective strategy to reduce heterogeneity to identify novel ASD genes. Numerous lines of evidence suggest a link between hyperserotonemia, i.e., elevated serotonin (5-hydroxytryptamine or 5-HT) in whole blood, and ASD. However, the genetic determinants of blood 5-HT level and their relationship to ASD are largely unknown...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28344334/the-kif1a-homolog-unc-104-is-important-for-spontaneous-release-postsynaptic-density-maturation-and-perisynaptic-scaffold-organization
#2
Yao V Zhang, Shabab B Hannan, Jeannine V Kern, Doychin T Stanchev, Baran Koç, Thomas R Jahn, Tobias M Rasse
The kinesin-3 family member KIF1A has been shown to be important for experience dependent neuroplasticity. In Drosophila, amorphic mutations in the KIF1A homolog unc-104 disrupt the formation of mature boutons. Disease associated KIF1A mutations have been associated with motor and sensory dysfunctions as well as non-syndromic intellectual disability in humans. A hypomorphic mutation in the forkhead-associated domain of Unc-104, unc-104(bris), impairs active zone maturation resulting in an increased fraction of post-synaptic glutamate receptor fields that lack the active zone scaffolding protein Bruchpilot...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28343185/frameworking-memory-and-serotonergic-markers
#3
Alfredo Meneses
The evidence for neural markers and memory is continuously being revised, and as evidence continues to accumulate, herein, we frame earlier and new evidence. Hence, in this work, the aim is to provide an appropriate conceptual framework of serotonergic markers associated with neural activity and memory. Serotonin (5-hydroxytryptamine [5-HT]) has multiple pharmacological tools, well-characterized downstream signaling in mammals' species, and established 5-HT neural markers showing new insights about memory functions and dysfunctions, including receptors (5-HT1A/1B/1D, 5-HT2A/2B/2C, and 5-HT3-7), transporter (serotonin transporter [SERT]) and volume transmission present in brain areas involved in memory...
March 27, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28343184/regulatory-role-of-ngfs-in-neurocognitive-functions
#4
Ashutosh Kumar, Vikas Pareek, Muneeb A Faiq, Pavan Kumar, Khursheed Raza, Pranav Prasoon, Subrahamanyam Dantham, Sankat Mochan
Nerve growth factors (NGFs), especially the prototype NGF and brain-derived neurotrophic factor (BDNF), have a diverse array of functions in the central nervous system through their peculiar set of receptors and intricate signaling. They are implicated not only in the development of the nervous system but also in regulation of neurocognitive functions like learning, memory, synaptic transmission, and plasticity. Evidence even suggests their role in continued neurogenesis and experience-dependent neural network remodeling in adult brain...
March 27, 2017: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/28342942/the-nature-of-early-astroglial-protection-fast-activation-and-signaling
#5
REVIEW
Julianna Kardos, László Héja, Katalin Jemnitz, Richárd Kovács, Miklós Palkovits
Our present review is focusing on the uniqueness of balanced astroglial signaling. The balance of excitatory and inhibitory signaling within the CNS is mainly determined by sharp synaptic transients of excitatory glutamate (Glu) and inhibitory γ-aminobutyrate (GABA) acting on the sub-second timescale. Astroglia is involved in excitatory chemical transmission by taking up i) Glu through neurotransmitter-sodium transporters, ii) K(+) released due to presynaptic action potential generation, and iii) water keeping osmotic pressure...
March 22, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28341205/autism-like-behavior-in-the-btbr-mouse-model-of-autism-is-improved-by-propofol
#6
Yulong Cai, Lian Wang, Rui Xiao, Xin Li, Xie He, Junwei Gao, Haiwei Xu, Xiaotang Fan
Autism spectrum disorder (ASD) is a developmental disorder that is characterized by symptoms of impaired social interactions, restricted interests and repetitive behaviors. Recent studies in humans and animal-models suggest that reduced GABAergic neurotransmission in the brain may underlie autism-related behavioral symptoms. It has been shown that propofol, a commonly used anesthetic, facilitates γ-aminobutyric acid-mediated inhibitory synaptic transmission. The present study investigated whether propofol improved autistic phenotypes in BTBR T + Itpr3tf/J (BTBR) mice, a model of idiopathic autism...
March 21, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28336440/astroglial-ca-2-signaling-is-generated-by-the-coordination-of-ip3r-and-store-operated-ca-2-channels
#7
Shigeo Sakuragi, Fumihiro Niwa, Yoichi Oda, Hiroko Bannai, Katsuhiko Mikoshiba
Astrocytes play key roles in the central nervous system and regulate local blood flow and synaptic transmission via intracellular calcium (Ca(2+)) signaling. Astrocytic Ca(2+) signals are generated by multiple pathways: Ca(2+) release from the endoplasmic reticulum (ER) via the inositol 1, 4, 5-trisphosphate receptor (IP3R) and Ca(2+) influx through various Ca(2+) channels on the plasma membrane. However, the Ca(2+) channels involved in astrocytic Ca(2+) homeostasis or signaling have not been fully characterized...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28335379/the-role-of-adenosine-signaling-in-headache-a-review
#8
REVIEW
Nathan T Fried, Melanie B Elliott, Michael L Oshinsky
Migraine is the third most prevalent disease on the planet, yet our understanding of its mechanisms and pathophysiology is surprisingly incomplete. Recent studies have built upon decades of evidence that adenosine, a purine nucleoside that can act as a neuromodulator, is involved in pain transmission and sensitization. Clinical evidence and rodent studies have suggested that adenosine signaling also plays a critical role in migraine headache. This is further supported by the widespread use of caffeine, an adenosine receptor antagonist, in several headache treatments...
March 13, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28334604/the-potential-role-of-gap-junctional-plasticity-in-the-regulation-of-state
#9
REVIEW
Philippe Coulon, Carole E Landisman
Electrical synapses are the functional correlate of gap junctions and allow transmission of small molecules and electrical current between coupled neurons. Instead of static pores, electrical synapses are actually plastic, similar to chemical synapses. In the thalamocortical system, gap junctions couple inhibitory neurons that are similar in their biochemical profile, morphology, and electrophysiological properties. We postulate that electrical synaptic plasticity among inhibitory neurons directly interacts with the switching between different firing patterns in a state-dependent and type-dependent manner...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28334377/lrit3-differentially-affects-connectivity-and-synaptic-transmission-of-cones-to-on-and-off-bipolar-cells
#10
Marion Neuillé, Yan Cao, Romain Caplette, Debbie Guerrero-Given, Connon Thomas, Naomi Kamasawa, José-Alain Sahel, Christian P Hamel, Isabelle Audo, Serge Picaud, Kirill A Martemyanov, Christina Zeitz
Purpose: Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). Using a cCSNB mouse model lacking Lrit3 (nob6), we recently have shown that LRIT3 has a role in the correct localization of TRPM1 (transient receptor potential melastatin 1) to the dendritic tips of ON-bipolar cells (BCs), contacting both rod and cone photoreceptors. Furthermore, postsynaptic clustering of other mGluR6 cascade components is selectively eliminated at the dendritic tips of cone ON-BCs...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28334325/endocannabinoid-dependent-long-term-potentiation-of-synaptic-transmission-at-rat-barrel-cortex
#11
Laura Eva Maglio, José Antonio Noriega-Prieto, Maria Jesús Maraver, David Fernández de Sevilla
Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition...
March 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28334166/grk5-regulates-social-behavior-via-suppression-of-mtorc1-signaling-in-medial-prefrontal-cortex
#12
Bing Niu, Peipei Liu, Minjie Shen, Cao Liu, Li Wang, Feifei Wang, Lan Ma
Impairments in social behaviors are features of a number of psychiatric diseases associated with subtle alterations in the medial prefrontal cortex (mPFC) circuitry. G protein-coupled receptor kinase (GRK) 5 is widely expressing in the cortex, however, its role in regulation of the mPFC activity and the development of social behaviors and psychiatric disorders is unclear. Here, we found that GRK5 dificiency in mice caused social behavior impairments. Further morphological, electrophysiological, and biochemical analyses showed abnormal postsynaptic ultrastructure, impaired excitatory synaptic transmission, the increased association of raptor with mTOR, and overactivated mTORC1-S6K signaling in the mPFC of Grk5-/- mice...
February 27, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28334103/neuronal-and-peripheral-pentraxins-modify-glutamate-release-and-may-interact-in-blood-brain-barrier-failure
#13
Damian M Cummings, Tiffanie A Benway, Hinze Ho, Angelo Tedoldi, Monica M Fernandes Freitas, Lion Shahab, Christina E Murray, Angela Richard-Loendt, Sebastian Brandner, Tammaryn Lashley, Dervis A Salih, Frances A Edwards
Neuronal pentraxin 1 (NPTX1) has been implicated in Alzheimer's disease, being present in and around dystrophic neurons in plaques, affecting glutamatergic transmission postsynaptically and mediating effects of amyloidβ. Here, we confirm the presence of NPTX1 around plaques in postmortem Alzheimer's disease brain and report that acutely applied human NPTX1 increases paired-pulse ratio at mouse CA3-CA1 hippocampal synapses, indicating a decrease in glutamate release. In contrast, chronic exposure to NPTX1, NPTX2, or NPTX receptor decreases paired-pulse ratio, mimicking some of the earliest changes in mice expressing familial Alzheimer's disease genes...
February 23, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28328738/inhibition-of-hippocampal-long-term-potentiation-by-high-fat-diets-is-it-related-to-an-effect-of-palmitic-acid-involving-glycogen-synthase-kinase-3
#14
Ana Contreras, Danila Del Rio, Ana Martínez, Carmen Gil, Lidia Morales, Mariano Ruiz-Gayo, Nuria Del Olmo
High-fat diets (HFD) impair hippocampal-dependent learning and memory and produce important changes in synaptic transmission by enhancing glutamate uptake, decreasing synaptic efficacy, and inhibiting plasticity mechanisms such as N-methyl-D-aspartate-mediated long-term depression (LTD) within the hippocampus. Adolescent animals seem to be particularly susceptible to the detrimental effect of HFD as dietary treatments carried out between weaning and early adulthood are much more efficient in terms of hippocampal damage that those carried out during the adult period...
March 21, 2017: Neuroreport
https://www.readbyqxmd.com/read/28326934/activations-of-muscarinic-m1-receptors-in-the-anterior-cingulate-cortex-contribute-to-the-antinociceptive-effect-via-gabaergic-transmission
#15
Kohei Koga, Yu Matsuzaki, Kenji Honda, Fumihiro Eto, Tomonori Furukawa, Keisuke Migita, Keiichi Irie, Kenichi Mishima, Shinya Ueno
Background Cholinergic systems regulate the synaptic transmission resulting in the contribution of the nociceptive behaviors. Anterior cingulate cortex is a key cortical area to play roles in nociception and chronic pain. However, the effect of the activation of cholinergic system for nociception is still unknown in the cortical area. Here, we tested whether the activation of cholinergic receptors can regulate nociceptive behaviors in adult rat anterior cingulate cortex by integrative methods including behavior, immunohistochemical, and electrophysiological methods...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326932/a-critical-role-of-spinal-shank2-proteins-in-nmda-induced-pain-hypersensitivity
#16
Seo-Yeon Yoon, Soon-Gu Kwon, Yong Ho Kim, Ji-Hee Yeo, Hyoung-Gon Ko, Dae-Hyun Roh, Bong-Kiun Kaang, Alvin J Beitz, Jang-Hern Lee, Seog Bae Oh
Background Self-injurious behaviors (SIBs) are devastating traits in autism spectrum disorder (ASD). Although deficits in pain sensation might be one of the contributing factors underlying the development of SIBs, the mechanisms have yet to be addressed. Recently, the Shank2 synaptic protein has been considered to be a key component in ASD, and mutations of SHANK2 gene induce the dysfunction of N-methyl-D-aspartate (NMDA) receptors, suggesting a link between Shank2 and NMDA receptors in ASD. Given that spinal NMDA receptors play a pivotal role in pain hypersensitivity, we investigated the possible role of Shank2 in nociceptive hypersensitivity by examining changes in spontaneous pain following intrathecal NMDA injection in S hank2-/- ( Shank2 knock-out, KO) mice...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28325932/a-stochastic-model-of-active-zone-material-mediated-synaptic-vesicle-docking-and-priming-at-resting-active-zones
#17
Jae Hoon Jung, Sebatian Doniach
Synaptic vesicles (SVs) fuse with the presynaptic membrane (PM) at specialized regions called active zones for synaptic transmission. SVs are associated with dense aggregates of macromolecules called active zone material (AZM) that has been thought to be involved in SV release. However, its role has recently begun to be elucidated. Several morphological studies proposed distinctively different AZM mediated SV docking and priming models: sequential and concurrent SV docking/priming. To explore ways to reconcile the contradictory models we develop a stochastic AZM mediated SV docking and priming model...
March 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28325749/the-nca-1-and-nca-2-ion-channels-function-downstream-of-gq-and-rho-to-regulate-locomotion-in-caenorhabditis-elegans
#18
Irini Topalidou, Pin-An Chen, Kirsten Cooper, Shigeki Watanabe, Erik M Jorgensen, Michael Ailion
The heterotrimeric G protein Gq positively regulates neuronal activity and synaptic transmission. Previously, the Rho guanine nucleotide exchange factor Trio was identified as a direct effector of Gq that acts in parallel to the canonical Gq effector phospholipase C. Here we examine how Trio and Rho act to stimulate neuronal activity downstream of Gq in the nematode Caenorhabditis elegans Through two forward genetic screens, we identify the cation channels NCA-1 and NCA-2, orthologs of mammalian NALCN, as downstream targets of the Gq/Rho pathway...
March 21, 2017: Genetics
https://www.readbyqxmd.com/read/28322793/temporal-relation-between-neural-activity-and-neurite-pruning-on-a-numerical-model-and-a-microchannel-device-with-micro-electrode-array
#19
Yohei Kondo, Yuichiro Yada, Tatsuya Haga, Yuzo Takayama, Takuya Isomura, Yasuhiko Jimbo, Osamu Fukayama, Takayuki Hoshino, Kunihiko Mabuchi
Synapse elimination and neurite pruning are essential processes for the formation of neuronal circuits. These regressive events depend on neural activity and occur in the early postnatal days known as the critical period, but what makes this temporal specificity is not well understood. One possibility is that the neural activities during the developmentally regulated shift of action of GABA inhibitory transmission lead to the critical period. Moreover, it has been reported that the shifting action of the inhibitory transmission on immature neurons overlaps with synapse elimination and neurite pruning and that increased inhibitory transmission by drug treatment could induce temporal shift of the critical period...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28320843/distinct-actions-of-voltage-activated-ca-2-channel-block-on-spontaneous-release-at-excitatory-and-inhibitory-central-synapses
#20
Timur Tsintsadze, Courtney L Williams, Dennis Weingarten, Henrique von Gersdorff, Stephen M Smith
At chemical synapses, voltage-activated calcium channels (VACCs) mediate Ca(2+) influx to trigger action potential-evoked neurotransmitter release. However, the mechanisms by which Ca(2+) regulates spontaneous transmission have not been fully determined. We have shown that VACCs are a major trigger of spontaneous release at neocortical inhibitory synapses but not at excitatory synapses suggesting fundamental differences in spontaneous neurotransmission at GABAergic and glutamatergic synapses. Recently, VACC blockers were reported to reduce spontaneous release of glutamate and it was proposed that there was conservation of underlying mechanisms of neurotransmission at excitatory and inhibitory synapses...
March 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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