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https://www.readbyqxmd.com/read/28220990/oxidative-stress-serotonergic-changes-and-decreased-ultrasonic-vocalizations-in-a-mouse-model-of-smith-lemli-opitz-syndrome
#1
Navila F Sharif, Zeljka Korade, Ned A Porter, Harrison Fiona E
Smith Lemli Opitz syndrome is an inherited monogenic disorder in which mutations to the Dhcr7 gene lead to deficits in cholesterol synthesis. As a result, many patients suffer from gross physiological and neurological deficits. The purpose of this study was to identify a potential abnormal behavioral phenotype in a compound mutant mouse model for Smith Lemli Opitz disease (Dhcr7(Δ3)(-5/)(T93M) ) to further validate the model, and to provide potential targets for future therapeutic interventions. We also sought to identify some of the underlying changes in brain function that may be responsible for behavioral differences among groups...
February 21, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28220706/human-cannabinoid-receptor-2-ligand-interaction-motif-transmembrane-helix-2-cysteine-c2-59-89-as-determinant-of-classical-cannabinoid-agonist-activity-and-binding-pose
#2
Han Zhou, Yan Peng, Aneetha Halikhedkar, Pusheng Fan, David R Janero, Ganesh A Thakur, Richard Warren Mercier, Xin Sun, Xiaoyu Ma, Alexandros Makriyannis
Cannabinoid receptor 2 (CB2R)-dependent signaling is implicated in neuronal physiology and immune surveillance by brain microglia. Selective CB2R agonists hold therapeutic promise for inflammatory and other neurological disorders. Information on human CB2R (hCB2R) ligand-binding and functional domains is needed to inform the rational design and optimization of candidate drug-like hCB2R agonists. Prior demonstration that hCB2R transmembrane helix 2 (TMH2) cysteine C2.59(89) reacts with small-molecule methanethiosulfonates showed that this cysteine residue is accessible to sulfhydryl derivatization reagents...
February 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28220655/ppars-in-the-central-nervous-system-roles-in-neurodegeneration-and-neuroinflammation
#3
Juan M Zolezzi, Manuel J Santos, Sussy Bastías-Candia, Claudio Pinto, Juan A Godoy, Nibaldo C Inestrosa
Over 25 years have passed since peroxisome proliferators-activated receptors (PPARs), were first described. Like other members of the nuclear receptors superfamily, PPARs have been defined as critical sensors and master regulators of cellular metabolism. Recognized as ligand-activated transcription factors, they are involved in lipid, glucose and amino acid metabolism, taking part in different cellular processes, including cellular differentiation and apoptosis, inflammatory modulation and attenuation of acute and chronic neurological damage in vivo and in vitro...
February 20, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28220607/neurological-and-spinal-manifestations-of-the-ehlers-danlos-syndromes
#4
Fraser C Henderson, Claudiu Austin, Edward Benzel, Paolo Bolognese, Richard Ellenbogen, Clair A Francomano, Candace Ireton, Petra Klinge, Myles Koby, Donlin Long, Sunil Patel, Eric L Singman, Nicol C Voermans
The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression...
February 21, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28220064/effect-of-experimentally-induced-trunk-muscular-tensions-on-the-sit-to-stand-task-performance-and-associated-postural-adjustments
#5
Alain Hamaoui, Caroline Alamini-Rodrigues
It has been shown that increased muscular activity along the trunk is likely to impair body balance, but there is little knowledge about its consequences on more dynamic tasks. The purpose of this study was to determine the effect of unilateral and bilateral increases of muscular tension along the trunk on the sit-to-stand task (STS) performance and associated anticipatory postural adjustments (APAs). Twelve healthy females (23 ± 3 years, 163 ± 0.06 cm, 56 ± 9 kg), free of any neurological or musculoskeletal disorders, performed six trials of the STS at maximum speed, in seven experimental conditions varying the muscular tension along each side of the trunk, using a specific bimanual compressive load paradigm...
2017: Frontiers in Human Neuroscience
https://www.readbyqxmd.com/read/28219703/immunomodulatory-properties-of-1-2-dihydro-4-hydroxy-2-oxo-1-8-naphthyridine-3-carboxamide-derivative-vl15
#6
Anna Maria Malfitano, Chiara Laezza, Simone Bertini, Daniela Marasco, Tiziano Tuccinardi, Maurizio Bifulco, Clementina Manera
1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells (PBMC), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219316/from-disorder-to-mis-order-structural-aspects-of-pathogenic-oligomerization-in-conformational-diseases
#7
Chin Pang Benny Yiu, Yu Wai Chen
Proteins implicated in neurological conformational diseases contain substantial amounts of "intrinsic disorder". These native monomeric functional states may transit into some oligomeric states that have high β-sheet contents and seed the formation of insoluble amyloid fibrils. The prevailing view is that these "toxic" oligomers should be targeted for drug development. Here, an overview of the diseases was presented, within the general framework of the oligomerization of intrinsically disordered proteins. These systems pose some specific challenges to structural studies: the toxic oligomers are transient, low in concentration, and often need to be studied in a heterogeneous environment...
February 20, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28219280/disability-diversity-and-autism-philosophical-perspectives-on-health
#8
Lidia Ripamonti
This paper aims to explore the connection between health and developmental disorders, particularly in regard to the notion of 'neurodiversity', which considers high-functioning autism not as a lifelong disability but a neurological form within a diversity of human minds. In recent years, autistic activist movements have called for a more positive, humanizing, identity-first language when describing this condition, rejecting negative language such as 'disorder', 'deficit', and 'impairment', and instead describing autism as a way of being, part of one's personal identity, which does not always need to be cured...
April 2016: New Bioethics: a Multidisciplinary Journal of Biotechnology and the Body
https://www.readbyqxmd.com/read/28218498/optimization-of-bicyclic-lactam-derivatives-as-nmda-receptor-antagonists
#9
Margarida Espadinha, Jorge Dourado, Rocio Lajarin-Cuesta, Clara Herrera-Arozamena, Lidia Gonçalves, Maria Isabel Rodríguez-Franco, Cristobal de Los Rios, Maria M M Santos
N-Methyl-D-aspartate (NMDA) receptors are fundamental for the normal function of the central nerve system, and play an important role in memory and learning. An overactivation of these receptors will lead to neuronal loss associated with major neurological disorders, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and epilepsy. Herein, twenty two novel enantiopure bicyclic lactams were designed, synthesized, and evaluated as NMDA receptor antagonists. Most of the new compounds displayed NMDA receptor antagonism and, the most promising compound showed IC50 value in the same order of magnitude of memantine, a NMDA receptor antagonist used in the clinic for the treatment of Alzheimer's disease...
February 20, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28217084/nad-attenuates-bilirubin-induced-hyperexcitation-in-the-ventral-cochlear-nucleus-by-inhibiting-excitatory-neurotransmission-and-neuronal-excitability
#10
Min Liang, Xin-Lu Yin, Lu-Yang Wang, Wei-Hai Yin, Ning-Ying Song, Hai-Bo Shi, Chun-Yan Li, Shan-Kai Yin
Nicotinamide adenine dinucleotide (NAD+) is an important molecule with extensive biological functions in various cellular processes, including protection against cell injuries. However, little is known regarding the roles of NAD+ in neuronal excitation and excitotoxicity associated with many neurodegenerative disorders and diseases. Using patch-clamp recordings, we studied its potential effects on principal neurons in the ventral cochlear nucleus (VCN), which is particularly vulnerable to bilirubin excitotoxicity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28216256/kleine-levin-syndrome
#11
REVIEW
Olufunke Afolabi-Brown, Thornton B A Mason
Kleine-Levin syndrome (KLS) is a rare disorder characterized by discrete episodes of hypersomnia associated with cognitive and behavioural abnormalities, as well as normal alertness and function between episodes. The prevalence of KLS may be underestimated as it is often misdiagnosed and managed as another sleep disorder, neurological disorder or psychiatric condition. KLS is more typically seen in adolescence than at other ages, and is more common in males than in females. There are currently neither standard biomarkers nor specific imaging study findings, making the diagnosis of KLS a challenge...
December 23, 2016: Paediatric Respiratory Reviews
https://www.readbyqxmd.com/read/28215308/releasing-mechanism-of-neurotrophic-factors-via-polysialic-acid
#12
C Sato
Neurotrophins are well-characterized neurologically active molecules in the central nervous system. The regulation of these signaling molecules, which are involved in cell growth, differentiation, and survival, is critical for normal brain function. Among the different types of neurotrophins, brain-derived neurotrophic factor (BDNF) is involved in various brain functions, including memory consolidation, synaptic plasticity, and adult neurogenesis, and is therefore a key molecule for understanding comprehensive brain function and neurodevelopmental and psychiatric diseases...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28214921/vitamin-d-administration-during-pregnancy-as-prevention-for-pregnancy-neonatal-and-postnatal-complications
#13
REVIEW
Carol L Wagner, Bruce W Hollis, Kalliopi Kotsa, Hana Fakhoury, Spyridon N Karras
Pregnancy represents a time of rapid bodily change, which includes physical proportions, physiology and responsibility. At this context, maternal vitamin D stores have been the objective of extensive scientific research during the last decades, focusing on their potential effects on maternal an neonatal health. A growing body of observational studies indicated that maternal hypovitaminosis D (as defined by maternal 25-hydroxyvitamin D [25(OH)D] levels <20 ng/ml or <50 nmol/l) is a significant risk factor for adverse neonatal outcomes including asthma, multiple sclerosis and other neurological disorders...
February 18, 2017: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/28212850/human-astrocytes-in-the-diseased-brain
#14
Elena Dossi, Flora Vasile, Nathalie Rouach
Astrocytes are key active elements of the brain that contribute to information processing. They not only provide neurons with metabolic and structural support, but also regulate neurogenesis and brain wiring. Furthermore, astrocytes modulate synaptic activity and plasticity in part by controlling the extracellular space volume, as well as ion and neurotransmitter homeostasis. These findings, together with the discovery that human astrocytes display contrasting characteristics with their rodent counterparts, point to a role for astrocytes in higher cognitive functions...
February 13, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28212680/mecp2-mutations-progress-towards-understanding-and-treating-rett-syndrome
#15
Ruth R Shah, Adrian P Bird
Rett syndrome is a profound neurological disorder caused by mutations in the MECP2 gene, but preclinical research has indicated that it is potentially treatable. Progress towards this goal depends on the development of increasingly relevant model systems and on our improving knowledge of MeCP2 function in the brain.
February 17, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28212663/isolation-of-primary-microglia-from-the-human-post-mortem-brain-effects-of-ante-and-post-mortem-variables
#16
Mark R Mizee, Suzanne S M Miedema, Marlijn van der Poel, Adelia, Karianne G Schuurman, Miriam E van Strien, Jeroen Melief, Joost Smolders, Debbie A Hendrickx, Kirstin M Heutinck, Jörg Hamann, Inge Huitinga
Microglia are key players in the central nervous system in health and disease. Much pioneering research on microglia function has been carried out in vivo with the use of genetic animal models. However, to fully understand the role of microglia in neurological and psychiatric disorders, it is crucial to study primary human microglia from brain donors. We have developed a rapid procedure for the isolation of pure human microglia from autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection...
February 17, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28211814/are-major-dementias-triggered-by-poor-blood-flow-to-the-brain-theoretical-considerations
#17
Jack C de la Torre
There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP)...
February 15, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28211486/motor-phenotype-is-not-associated-with-vascular-dysfunction-in-symptomatic-huntington-s-disease-transgenic-r6-2-160-cag-mice
#18
A Di Pardo, A Carrizzo, A Damato, S Castaldo, E Amico, L Capocci, M Ambrosio, F Pompeo, C De Sanctis, C C Spinelli, A A Puca, P Remondelli, V Maglione, C Vecchione
Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28210955/the-effects-of-igf-1-on-tnf-%C3%AE-treated-drg-neurons-by-modulating-atf3-and-gap-43-expression-via-pi3k-akt-s6k-signaling-pathway
#19
Lei Zhang, Yaping Yue, Meishuo Ouyang, Huaxiang Liu, Zhenzhong Li
Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration...
February 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28209774/methyl-donor-supplementation-alters-cognitive-performance-and-motivation-in-female-offspring-from-high-fat-diet-fed-dams
#20
Sarah E McKee, Nicola M Grissom, Christopher T Herdt, Teresa M Reyes
During gestation, fetal nutrition is entirely dependent on maternal diet. Maternal consumption of excess fat during pregnancy has been linked to an increased risk of neurologic disorders in offspring, including attention deficit/hyperactivity disorder, autism, and schizophrenia. In a mouse model, high-fat diet (HFD)-fed offspring have cognitive and executive function deficits as well as whole-genome DNA and promoter-specific hypomethylation in multiple brain regions. Dietary methyl donor supplementation during pregnancy or adulthood has been used to alter DNA methylation and behavior...
February 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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