Search results for " DISORDERS"
showing 10 items of 4492 documents
Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts
2016
The research leading to these results was funded by the Spanish Ministry of Health (FIS-PI11/00610, FIS-PI041436, FIS-PI081151, FIS-PI042018, and FIS-PI09/02311), the European Union (EU) (FP7-ENV-2011 cod 282957 and HEALTH.2010.2.4.5-1), the Instituto de Salud Carlos III (Red INMA G03/176, CB06/02/0041, FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, 09/02647, 11/01007, 11/02591, CP11/00178, FIS-PI06/0867, and FIS-PS09/00090), the Conselleria de Sanitat Generalitat Valenciana, the Generalitat de Catalunya-CIRIT (1999SGR 00241), the Obre Social Cajastur, the Universidad de Oviedo, the Department of Health of the Basque Government (2005111093 and 2009111069),…
NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
2018
Background: NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in 50% of affected individuals. Numerous additional symptoms may be associated, although many of these were reported only in single cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency previously. Case Presentation: We examined two members of a family with motor developmental delay, mixed movement disorder (myoclonus, dyst…
The Effects of N-Acetylcysteine on the Rat Mesocorticolimbic Pathway: Role of mGluR5 Receptors and Interaction with Ethanol
2021
N-acetylcysteine (NAC) is a prodrug that is marketed as a mucolytic agent and used for the treatment of acetaminophen overdose. Over the last few decades, evidence has been gathered that suggests the potential use of NAC as a new pharmacotherapy for alcohol use disorder (AUD), although its mechanism of action is already being debated. In this paper, we set out to assess both the potential involvement of the glutamate metabotropic receptors (mGluR) in the possible dual effect of NAC administered at two different doses and NAC’s effect on ethanol-induced activation. To this aim, 30 or 120 mg/kg of NAC was intraperitoneally administered to rats with the presence or absence of the negative allo…
Differential glutamatergic and GABAergic contributions to the tetrad effects of Δ9-tetrahydrocannabinol revealed by cell-type-specific reconstitution…
2020
Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of Cannabis sativa, exerts its actions through the endocannabinoid system by stimulation of the cannabinoid type 1 (CB1) receptor. The widespread distribution of this receptor in different neuronal cell types and the plethora of functions that is modulated by the endocannabinoid system explain the versatility of the effects of THC. However, the cell types involved in the different THC effects are still not fully known. Conditional CB1 receptor knock-out mice were previously used to identify CB1 receptor subpopulations that are "necessary" for the tetrad effects of a high dose of THC: hypothermia, hypolocomotion, catalepsy and …
2019
Background: Focal dystonias are severe and disabling movement disorders of a still unclear origin. The structural brain networks associated with focal dystonia have not been well characterized. Here, we investigated structural brain network fingerprints in patients with blepharospasm (BSP) compared with those with hemifacial spasm (HFS), and healthy controls (HC). The patients were also examined following treatment with botulinum neurotoxin (BoNT). Methods: This study included matched groups of 13 BSP patients, 13 HFS patients, and 13 HC. We measured patients using structural-magnetic resonance imaging (MRI) at baseline and after one month BoNT treatment, at time points of maximal and minim…
Linoleic acid: Is this the key that unlocks the quantum brain? Insights linking broken symmetries in molecular biology, mood disorders and personalis…
2017
Abstract In this paper we present a mechanistic model that integrates subneuronal structures, namely ion channels, membrane fatty acids, lipid rafts, G proteins and the cytoskeleton in a dynamic system that is finely tuned in a healthy brain. We also argue that subtle changes in the composition of the membrane’s fatty acids may lead to down-stream effects causing dysregulation of the membrane, cytoskeleton and their interface. Such exquisite sensitivity to minor changes is known to occur in physical systems undergoing phase transitions, the simplest and most studied of them is the so-called Ising model, which exhibits a phase transition at a finite temperature between an ordered and disorde…
Effect of ω-3 Polyunsaturated Fatty Acids-Derived Bioactive Lipids on Metabolic Disorders
2021
Arachidonic acid (ARA) is an important ω-6 polyunsaturated fatty acid (PUFA), and docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) and n-3 docosapentaenoic acid (n-3 DPA) are three well-known ω-3 PUFAs. These fatty acids can be metabolized into a number of bioactive lipids. Eicosanoids derived from ARA have drawn great attention because of their important and complex biofunctions. Although EPA, DHA and n-3 DPA have also shown powerful biofunctions, we have fewer studies of metabolites derived from them than those from ARA. Recently, growing research has focused on the bioaction of ω-3 PUFA-derived metabolites, which indicates their great potential for treating metabolic disorders. Mo…
A conditional inducible JAK2V617F transgenic mouse model reveals myeloproliferative disease that is reversible upon switching off transgene expressio…
2019
Aberrant activation of the JAK/STAT pathway is thought to be the critical event in the pathogenesis of the chronic myeloproliferative neoplasms, polycythemia vera, essential thrombocythemia and primary myelofibrosis. The most frequent genetic alteration in these pathologies is the activating JAK2V617F mutation, and expression of the mutant gene in mouse models was shown to cause a phenotype resembling the human diseases. Given the body of genetic evidence, it has come as a sobering finding that JAK inhibitor therapy only modestly suppresses the JAK2V617F allele burden, despite showing clear benefits in terms of reducing splenomegaly and constitutional symptoms in patients. To gain a better …
Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated social defeat
2018
It is well established that repeated social defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or social defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each social defeat or exploration episode. Three weeks after the last social defeat, anxiety was evaluated using an elevated plus maze paradigm. After this tes…
Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders
2020
A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of dive…