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https://www.readbyqxmd.com/read/29785841/effects-of-antipsychotic-drugs-on-neurites-relevant-to-schizophrenia-treatment
#1
REVIEW
Xu-Feng Huang, Xueqin Song
Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia...
May 22, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29784826/deletion-of-lrrtm1-and-lrrtm2-in-adult-mice-impairs-basal-ampa-receptor-transmission-and-ltp-in-hippocampal-ca1-pyramidal-neurons
#2
Mehdi Bhouri, Wade Morishita, Paul Temkin, Debanjan Goswami, Hiroshi Kawabe, Nils Brose, Thomas C Südhof, Ann Marie Craig, Tabrez J Siddiqui, Robert Malenka
Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse ( LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29782484/implications-for-human-odor-sensing-revealed-from-the-statistics-of-odorant-receptor-interactions
#3
Ji Hyun Bak, Seogjoo J Jang, Changbong Hyeon
Binding of odorants to olfactory receptors (ORs) elicits downstream chemical and neural signals, which are further processed to odor perception in the brain. Recently, Mainland and colleagues have measured more than 500 pairs of odorant-OR interaction by a high-throughput screening assay method, opening a new avenue to understanding the principles of human odor coding. Here, using a recently developed minimal model for OR activation kinetics, we characterize the statistics of OR activation by odorants in terms of three empirical parameters: the half-maximum effective concentration EC50, the efficacy, and the basal activity...
May 21, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29781215/strap-deficiency-impairs-mouse-embryonic-stem-cells-lineage-commitment-through-cyp26a1-mediated-retinoic-acid-homeostasis
#4
Lin Jin, Chenbei Chang, Kevin M Pawlik, Arunima Datta, Larry M Johnson, Trung Vu, Joseph L Napoli, Pran K Datta
Retinoic acid (RA) signaling is essential for the differentiation of embryonic stem cells (ESCs) and vertebrate development. RA biosynthesis and metabolism are controlled by a series of enzymes, but the molecular regulators of these enzymes remain largely obscure. In this study, we investigated the functional role of the WD-domain protein STRAP (serine threonine kinase receptor-associated protein) in the pluripotency and lineage commitment of murine ESCs. We generated Strap knockout (KO) mouse ESCs and subjected them to spontaneous differentiation...
May 21, 2018: Stem Cells
https://www.readbyqxmd.com/read/29780321/toll-like-receptor-2-signaling-and-current-approaches-for-therapeutic-modulation-in-synucleinopathies
#5
REVIEW
Ian F Caplan, Kathleen A Maguire-Zeiss
The innate immune response in the central nervous system (CNS) is implicated as both beneficial and detrimental to health. Integral to this process are microglia, the resident immune cells of the CNS. Microglia express a wide variety of pattern-recognition receptors, such as Toll-like receptors, that detect changes in the neural environment. The activation of microglia and the subsequent proinflammatory response has become increasingly relevant to synucleinopathies, including Parkinson's disease the second most prevalent neurodegenerative disease...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29779467/calcium-sodium-and-trp-channel-expression-in-human-fetal-midbrain-derived-neural-progenitor-cells
#6
Nancy Stanslowsky, Salini Tharmarasa, Selma Staege, Norman Kalmbach, Martin Klietz, Sigrid Schwarz, Andreas Leffler, Florian Wegner
Voltage-gated sodium and calcium channels as well as transient receptor potential (TRP) channels are expressed during the differentiation of human neural progenitor cells (hNPCs) and are likely to be involved in regulating neurogenesis. However, the molecular composition of these ion channels in proliferating and differentiating hNPCs is largely unknown. Here, we investigated fetal mesencephalic hNPCs in respect to their sodium, calcium, and TRP channel subunit expression and function. Quantitative real-time PCR indicated a significant upregulation of voltage-gated sodium and calcium channel subunits in hNPCs after differentiation for 3 weeks in vitro...
May 19, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29778010/exposure-to-cannabinoid-agonist-win-55-212-2-during-early-adolescence-increases-alcohol-preference-and-anxiety-in-cd1-mice
#7
Jimena Laura Frontera, Victoria María Gonzalez Pini, Fernando Luis Messore, Alicia Brusco
The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence...
May 16, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29777722/ca-2-signaling-and-spinocerebellar-ataxia
#8
REVIEW
Chihiro Hisatsune, Kozo Hamada, Katsuhiko Mikoshiba
Spinocerebellar ataxia (SCA) is a neural disorder, which is caused by degenerative changes in the cerebellum. SCA is primarily characterized by gait ataxia, and additional clinical features include nystagmus, dysarthria, tremors and cerebellar atrophy. Forty-four hereditary SCAs have been identified to date, along with >35 SCA-associated genes. Despite the great diversity and distinct functionalities of the SCA-related genes, accumulating evidence supports the occurrence of a common pathophysiological event among several hereditary SCAs...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29776968/liraglutide-modulates-appetite-and-body-weight-via-glp-1r-expressing-glutamatergic-neurons
#9
Jessica M Adams, Hongjuan Pei, Darleen A Sandoval, Randy J Seeley, Rui B Chang, Stephen D Liberles, David P Olson
Glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) impact appetite and body weight are still not fully understood. Here, we determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the acute and chronic effects of the GLP1RA liraglutide on food intake, visceral illness, body weight and neural network activation. We found that mice lacking GLP-1Rs in vGAT -expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2 -expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding...
May 18, 2018: Diabetes
https://www.readbyqxmd.com/read/29775678/synaptic-transmission-and-excitability-during-hypoxia-with-inflammation-and-reoxygenation-in-hippocampal-ca1-neurons
#10
Yoon-Sil Yang, Sook Jin Son, Joon Ho Choi, Jong-Cheol Rah
Although a number of experimental and clinical studies have shown that hypoxia typically accompanies acute inflammatory responses, the combinatorial effect of the two insults on basic neural function has not been thoroughly investigated. Previous studies have predominantly suggested that hypoxia reduces network activity; however, several studies suggest the opposite effect. Of note, inflammation is known to increase neural activity. In the current study, we examined the effects of limited oxygen in combination with an inflammatory stimulus, as well as the effects of reoxygenation, on synaptic transmission and excitability...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29775595/the-neuropeptide-tac2-controls-a-distributed-brain-state-induced-by-chronic-social-isolation-stress
#11
Moriel Zelikowsky, May Hui, Tomomi Karigo, Andrea Choe, Bin Yang, Mario R Blanco, Keith Beadle, Viviana Gradinaru, Benjamin E Deverman, David J Anderson
Chronic social isolation causes severe psychological effects in humans, but their neural bases remain poorly understood. 2 weeks (but not 24 hr) of social isolation stress (SIS) caused multiple behavioral changes in mice and induced brain-wide upregulation of the neuropeptide tachykinin 2 (Tac2)/neurokinin B (NkB). Systemic administration of an Nk3R antagonist prevented virtually all of the behavioral effects of chronic SIS. Conversely, enhancing NkB expression and release phenocopied SIS in group-housed mice, promoting aggression and converting stimulus-locked defensive behaviors to persistent responses...
May 17, 2018: Cell
https://www.readbyqxmd.com/read/29775479/acute-intermittent-hypoxia-and-rehabilitative-training-following-cervical-spinal-injury-alters-neuronal-hypoxia-and-plasticity-associated-protein-expression
#12
Atiq Hassan, Breanna M Arnold, Sally Caine, Behzad M Toosi, Valerie M K Verge, Gillian D Muir
One of the most promising approaches to improve recovery after spinal cord injury (SCI) is the augmentation of spontaneously occurring plasticity in uninjured neural pathways. Acute intermittent hypoxia (AIH, brief exposures to reduced O2 levels alternating with normal O2 levels) initiates plasticity in respiratory systems and has been shown to improve recovery in respiratory and non-respiratory spinal systems after SCI in experimental animals and humans. Although the mechanism by which AIH elicits its effects after SCI are not well understood, AIH is known to alter protein expression in spinal neurons in uninjured animals...
2018: PloS One
https://www.readbyqxmd.com/read/29771559/body-mass-index-across-adolescence-and-substance-use-problems-in-early-adulthood
#13
Ashley N Gearhardt, Rebecca Waller, Jennifer M Jester, Luke W Hyde, Robert A Zucker
Excessive substance use and obesity are underpinned by a number of shared risk factors (e.g., reward dysfunction, impulsivity). Food and drugs of abuse engage similar reward-related neural circuitry and the food-drug competition hypothesis proposes that excess consumption of food may diminish desire for drugs of abuse by competing for neural receptors associated with reward and motivation. Adolescence is a high-risk period for both increased substance use and excessive weight gain. In the present study, the authors tested whether, consistent with the food-drug competition hypothesis, elevated body mass index (BMI) across adolescence predicted fewer substance use problems in young adulthood...
May 2018: Psychology of Addictive Behaviors: Journal of the Society of Psychologists in Addictive Behaviors
https://www.readbyqxmd.com/read/29771335/loss-of-fragile-x-protein-fmrp-impairs-homeostatic-synaptic-downscaling-through-tumor-suppressor-p53-and-ubiquitin-e3-ligase-nedd4-2
#14
Kwan Young Lee, Kathryn A Jewett, Hee Jung Chung, Nien-Pei Tsai
Synaptic scaling allows neurons to homeostatically readjust synaptic strength upon chronic neural activity perturbations. Although altered synaptic scaling has been implicated to underlie imbalanced brain excitability in neurological disorders such as autism spectrum disorders and epilepsy, the molecular dysregulation and restoration of synaptic scaling in those diseases have not been demonstrated. Here, we showed that the homeostatic synaptic downscaling is absent in the hippocampal neurons of Fmr1 KO mice, the mouse model of the most common inherited autism, Fragile X Syndrome (FXS)...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29771302/physical-linkage-of-estrogen-receptor-%C3%AE-and-aromatase-in-rat-oligocrine-and-endocrine-actions-of-cns-produced-estrogens
#15
Emiliya M Storman, Nai-Jiang Liu, Martin W Wessendorf, Alan R Gintzler
Rapid-signaling membrane estrogen receptors and aromatase are present throughout the central nervous system (CNS), enabling acute regulation of CNS estrogenic signaling. We previously reported that spinal membrane aromatase (mAro) and membrane estrogen receptor α (mERα) oligomerize (1). Since their organizational relationship would likely influence functions of locally produced estrogens, we quantified the mAro and mERα that are physically associated and non-associated in two functionally different regions of rat CNS - spinal cord, which has predominantly neural functionalities, and hypothalamus, which has both neural and endocrine capabilities...
May 15, 2018: Endocrinology
https://www.readbyqxmd.com/read/29770921/neuronal-adenosine-a-2a-receptor-overexpression-is-neuroprotective-towards-3-nitropropionic-acid-induced-striatal-toxicity-a-rat-model-of-huntington-s-disease
#16
Maria Rosaria Domenici, Valentina Chiodi, Mirko Averna, Monica Armida, Antonella Pèzzola, Rita Pepponi, Antonella Ferrante, Michael Bader, Kjell Fuxe, Patrizia Popoli
The A2A adenosine receptor (A2A R) is widely distributed on different cellular types in the brain, where it exerts a broad spectrum of pathophysiological functions, and for which a role in different neurodegenerative diseases has been hypothesized or demonstrated. To investigate the role of neuronal A2A Rs in neurodegeneration, we evaluated in vitro and in vivo the effect of the neurotoxin 3-nitropropionic acid (3-NP) in a transgenic rat strain overexpressing A2A Rs under the control of the neural-specific enolase promoter (NSEA2A rats)...
May 16, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29768254/neuroprotection-against-hypoxic-ischemic-injury-%C3%AE-opioid-receptors-and-bdnf-trkb-pathway
#17
Shiying Sheng, Jingzhong Huang, Yi Ren, Feng Zhi, Xuansong Tian, Guoqiang Wen, Guanghong Ding, Terry C Xia, Fei Hua, Ying Xia
The delta-opioid receptor (DOR) is one of three classic opioid receptors in the opioid system. It was traditionally thought to be primarily involved in modulating the transmission of messages along pain signaling pathway. Although there were scattered studies on its other neural functions, inconsistent results and contradicting conclusions were found in past literatures, especially in terms of DOR's role in a hypoxic/ischemic brain. Taking inspiration from the finding that the turtle brain exhibits a higher DOR density and greater tolerance to hypoxic/ischemic insult than the mammalian brain, we clarified DOR's specific role in the brain against hypoxic/ischemic injury and reconciled previous controversies in this aspect...
May 11, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29765302/the-role-of-actin-cytoskeleton-in-dendritic-spines-in-the-maintenance-of-long-term-memory
#18
REVIEW
Sreetama Basu, Raphael Lamprecht
Evidence indicates that long-term memory formation involves alterations in synaptic efficacy produced by modifications in neural transmission and morphology. However, it is not clear how such alterations induced by learning, that encode memory, are maintained over long period of time to preserve long-term memory. This is especially intriguing as the half-life of most of the proteins that underlie such changes is usually in the range of hours to days and these proteins may change their location over time. In this review we describe studies that indicate the involvement of dendritic spines in memory formation and its maintenance...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29763633/estradiol-induced-enhancement-of-fear-extinction-in-female-rats-the-role-of-nmda-receptor-activation
#19
Bronwyn M Graham, Elliot Scott
Converging cross-species evidence indicates that fear extinction (the laboratory basis of exposure therapy for anxiety disorders) in females is modulated by endogenous and exogenous estradiol. The mechanisms underlying estradiol's influences on fear extinction are largely undefined. However, one likely candidate is the NMDA-receptor (NMDAr), activation of which is necessary for estradiol-mediated enhancements in structural and functional neural plasticity, as well as extinction consolidation in males. Here, we demonstrate that systemic co-administration of the non-competitive NMDAr antagonist, MK801, blocked the enhancement of fear extinction by systemic estradiol in ovariectomized rats...
May 12, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29761600/loss-of-angiotensin-converting-enzyme-2-exacerbates-diabetic-retinopathy-by-promoting-bone-marrow-dysfunction
#20
Yaqian Duan, Eleni Beli, Sergio Li Calzi, Judith L Quigley, Rehae C Miller, Leni Moldovan, Dongni Feng, Tatiana E Salazar, Sugata Hazra, Jude Al-Sabah, Kakarla V Chalam, Thao Le Phuong Trinh, Marya Meroueh, Troy A Markel, Matthew C Murray, Ruchi J Vyas, Michael E Boulton, Patricia Parsons-Wingerter, Gavin Y Oudit, Alexander G Obukhov, Maria B Grant
Angiotensin-converting enzyme 2 (ACE2) is the primary enzyme of the vasoprotective axis of the renin angiotensin system (RAS). We tested the hypothesis that loss of ACE2 would exacerbate diabetic retinopathy by promoting bone marrow dysfunction. ACE2-/y were crossed with Akita mice, a model of type 1 diabetes. When comparing the bone marrow of the ACE2-/y -Akita mice to that of Akita mice, we observed a reduction of both short-term and long-term repopulating hematopoietic stem cells, a shift of hematopoiesis towards myelopoiesis, and an impairment of lineage- c-kit+ hematopoietic stem/progenitor cell (HS/PC) migration and proliferation...
May 15, 2018: Stem Cells
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