766,321 results match your criteria synthesis brain

4,4'-Dimethoxychalcone regulates redox homeostasis by targeting riboflavin metabolism in Parkinson's disease therapy.

Free Radic Biol Med 2021 Jul 28. Epub 2021 Jul 28.

Institute of Neuroscience and the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, 510260, China. Electronic address:

Oxidative stress damage plays a pivotal role in Parkinson's disease (PD) pathogenesis. Previously, we developed a blood brain barrier-penetrating peptide-based "Trojan Horse" strategy to deliver 4,4'-dimethoxychalcone (DMC) for PD therapy and revealed neuroprotective properties of DMC in a PD model; however, the underlying mechanisms remained unclear. Here, we report that DMC attenuated motor impairment, degeneration of DA neurons and α-synuclein aggregation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and exogenous human α-synuclein-induced PD mouse models. Read More

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Peripheral Levels of C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β across the mood spectrum in bipolar disorder: a meta-analysis of mean differences and variability.

Brain Behav Immun 2021 Jul 28. Epub 2021 Jul 28.

Deakin University, IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, 75 Pigdon's Road, Waurn Ponds, Geelong, VIC, 3216, Australia. Electronic address:

Importance: It is unclear whether differences exist in the magnitude and variability of pro-inflammatory mediators in the different phases of bipolar disorder (BD) and among subjects with BD, as compared to healthy controls.

Objective: To run a comparative meta-analysis of C-Reactive Protein (CRP), IL-1, IL-6, TNF-α in BD vs healthy controls, measuring mean and variability effects on all subjects. Sensitivity analyses include disease activity. Read More

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The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity.

Metabolism 2021 Jul 28:154839. Epub 2021 Jul 28.

Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands. Electronic address:

Background And Aims: Serotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We therefore aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity. Read More

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Bone morphogenetic Proteins (BMPs) in the central regulation of energy balance and adult neural plasticity.

Metabolism 2021 Jul 28:154837. Epub 2021 Jul 28.

Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, United States of America; School of Biology and Ecology, University of Maine, Orono, ME, United States of America; Department of Neurological Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States of America. Electronic address:

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The crosstalk between brain and periphery: Implications for brain health and disease.

Neuropharmacology 2021 Jul 28:108728. Epub 2021 Jul 28.

Centre for Neuroscience Studies, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada; Department of Psychiatry, Queen's University, Kingston, ON K7L 3N6, Canada; D'Or Institute for Research and Education (IDOR), Rio de Janeiro, RJ, 22281-100, Brazil; Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, 21941-902, Brazil. Electronic address:

Mounting evidence indicates that signaling molecules identified primarily in the peripheral circulation can affect cognitive function in physiological and pathological conditions, including in the development of several neurological diseases. However, considering the properties of the vascular blood-brain barrier (BBB), circulating lipophobic molecules would not be expected to cross this vascular structure. Thus, if and how peripheral lipophobic molecules, such as hormones and cytokines, reach the brain to exert their reported effects remains to be better established. Read More

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Genetic analysis and prenatal diagnosis in a Chinese with growth retardation, abnormal liver function, and microcephaly.

Mol Genet Genomic Med 2021 Jul 31:e1751. Epub 2021 Jul 31.

Precision Medical Laboratory, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, PR China.

Background: Congenital disorders of glycosylation (CDG) are a genetically heterogeneous group of disorders caused by defects in the synthesis and processing of glycoproteins. COG6-CDG is a kind of disorder caused by conserved oligomeric golgi complex 6 (COG6) deficiency. To date, only 19 patients with COG6-CDG have been reported. Read More

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Structural and functional neuroimaging of late-life depression: a coordinate-based meta-analysis.

Brain Imaging Behav 2021 Jul 31. Epub 2021 Jul 31.

Institute of Medical Science and Technology, Shahid Beheshti University, Tehran, Iran.

Several neuroimaging studies have investigated localized aberrations in brain structure, function or connectivity in late-life depression, but the ensuing results are equivocal and often conflicting. Here, we provide a quantitative consolidation of neuroimaging in late-life depression using coordinate-based meta-analysis by searching multiple databases up to March 2020. Our search revealed 3252 unique records, among which we identified 32 eligible whole-brain neuroimaging publications comparing 674 patients with 568 controls. Read More

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Effects of the Mediterranean Diet or Nut Consumption On Gut Microbiota Composition and Fecal Metabolites and their Relationship With Cardiometabolic Risk Factors.

Mol Nutr Food Res 2021 Jul 31:e2000982. Epub 2021 Jul 31.

Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences, University RoviraiVirgili (URV), Reus, Spain.

Scope: To examine whether a Mediterranean Diet (MedDiet) compared to the consumption of nuts in the context of a habitual non-MedDiet exerts a greater beneficial effect on gut microbiota and fecal metabolites, thus contributing to explain major benefits on cardiometabolic risk factors.

Methods And Results: Fifty adults with Metabolic Syndrome were randomized to a controlled, crossover 2-months dietary-intervention trial with a 1-month wash-out period, following a MedDiet or consuming nuts (50 g/day). Microbiota composition was assessed by 16S rRNA gene sequencing and metabolites were measured using NMR and LC-qTOF platforms in a targeted metabolomics approach. Read More

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Effects of growth hormone-releasing hormone receptor antagonist MIA-602 in mice with emotional disorders: a potential treatment for PTSD.

Mol Psychiatry 2021 Jul 30. Epub 2021 Jul 30.

Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.

Anxiety and depression have been suggested to increase the risk for post-traumatic stress disorders (PTSD). A link between all these mental illnesses, inflammation and oxidative stress is also well established. Recent behavior studies by our group clearly demonstrate a powerful anxiolytic and antidepressant-like effects of a novel growth hormone releasing hormone (GHRH) antagonist of MIAMI class, MIA-690, probably related to modulatory effects on the inflammatory and oxidative status. Read More

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In vivo MRI evaluation of early postnatal development in normal and impaired rat eyes.

Sci Rep 2021 Jul 30;11(1):15513. Epub 2021 Jul 30.

Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA.

This study employed in vivo 7-T magnetic resonance imaging (MRI) to evaluate the postnatal ocular growth patterns under normal development or neonatal impairments in Sprague-Dawley rats. Using T2-weighted imaging on healthy rats from postnatal day (P) 1 (newborn) to P60 (adult), the volumes of the anterior chamber and posterior chamber (ACPC), lens, and vitreous humor increased logistically with ACPC expanding by 33-fold and the others by fivefold. Intravitreal potassium dichromate injection at P1, P7, and P14 led to T1-weighted signal enhancement in the developing retina by 188-289%. Read More

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Integration of segmented regression analysis with weighted gene correlation network analysis identifies genes whose expression is remodeled throughout physiological aging in mouse tissues.

Aging (Albany NY) 2021 Jul 29;13(undefined). Epub 2021 Jul 29.

Institute of Biomedicine - iBiMED, Department of Medical Sciences, University of Aveiro, Aveiro 3810-193, Portugal.

Gene expression alterations occurring with aging have been described for a multitude of species, organs, and cell types. However, most of the underlying studies rely on static comparisons of mean gene expression levels between age groups and do not account for the dynamics of gene expression throughout the lifespan. These studies also tend to disregard the pairwise relationships between gene expression profiles, which may underlie commonly altered pathways and regulatory mechanisms with age. Read More

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The effects of graded calorie restriction XVII: Multitissue metabolomics reveals synthesis of carnitine and NAD, and tRNA charging as key pathways.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing 100101, China;

The evolutionary context of why caloric restriction (CR) activates physiological mechanisms that slow the process of aging remains unclear. The main goal of this analysis was to identify, using metabolomics, the common pathways that are modulated across multiple tissues (brown adipose tissue, liver, plasma, and brain) to evaluate two alternative evolutionary models: the "disposable soma" and "clean cupboards" ideas. Across the four tissues, we identified more than 10,000 different metabolic features. Read More

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Attention deficit hyperactivity disorder: a rare clinical presentation of L-2-hydroxyglutaric aciduria.

BMJ Case Rep 2021 Jul 30;14(7). Epub 2021 Jul 30.

Pediatric Neurology and Neurodevelopmental Disorders, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India

L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder caused by the deficiency of L-2-hydroxyglutarate dehydrogenase (L2HGDH) enzyme. Dystonia, ataxia, pyramidal involvement and seizures are the common clinical manifestations. Coexisting behavioural problems and intellectual disability are also seen, however attention deficit hyperactivity disorder (ADHD) as the presenting clinical feature in L2HGA is rarely described. Read More

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The Names of Things: The 2018 Bernard Sachs Lecture.

William B Dobyns

Pediatr Neurol 2021 Jun 30. Epub 2021 Jun 30.

Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota. Electronic address:

In 2018, I was honored to receive the Bernard Sachs Award for a lifetime of work expanding knowledge of diverse neurodevelopmental disorders. Summarizing work over more than 30 years is difficult but is an opportunity to chronicle the dramatic changes in the medical and scientific world that have transformed the field of Child Neurology over this time, as reflected in my own work. Here I have chosen to highlight five broad themes of my research beginning with my interest in descriptive terms that drive wider understanding and my choice for the title of this review. Read More

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Maternal Metabolic Programming of the Developing Central Nervous System: Unified Pathways to Metabolic and Psychiatric Disorders.

Biol Psychiatry 2021 Jun 8. Epub 2021 Jun 8.

German Center for Diabetes Research, Neuherberg, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany; Policlinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital Cologne, Cologne, Germany. Electronic address:

The perinatal period presents a critical time in offspring development where environmental insults can have damaging impacts on the future health of the offspring. This can lead to sustained alterations in offspring development, metabolism, and predisposition to both metabolic and psychiatric diseases. The central nervous system is one of the most sensitive targets in response to maternal obesity and/or type 2 diabetes mellitus. Read More

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Synthesis and analysis of dihydrotetrabenazine derivatives as novel vesicular monoamine transporter 2 inhibitors.

Eur J Med Chem 2021 Jul 24;224:113718. Epub 2021 Jul 24.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China. Electronic address:

Vesicular monoamine transporter 2 (VMAT2) is essential for synaptic transmission of all biogenic amines in the brain including serotonin, norepinephrine, histamine, and dopamine (DA). Given its crucial role in the neurophysiology and pharmacology of the central nervous system, VMAT2 is recognized as an important therapeutic target for various neurological disorders such as tardive dyskinesia (TD). Here, a novel series of dihydrotetrabenazine derivative analogs were designed and synthesized to evaluate their effects on [H]dihydrotetrabenazine (DTBZ) binding and [H]DA uptake at VMAT2. Read More

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3-Methyl-imidazo[2,1-b]thiazole derivatives as a new class of antifolates: Synthesis, in vitro/in vivo bio-evaluation and molecular modeling simulations.

Bioorg Chem 2021 Jul 24;115:105205. Epub 2021 Jul 24.

Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.. Electronic address:

Inhibiting the Dihydrofolate reductase (DHFR) enzyme has been validated in multiple clinical manifestations related to bacterial infection, malaria, and multiple types of cancer. Herein, novel series of 3-methyl-imidazo[2,1-b] thiazole-based analogs were synthesized and biologically evaluated for their in vitro inhibitory profile towards DHFR. Compounds 22 and 23 exhibited potent inhibitory profile targeting DHFR (IC 0. Read More

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RNA-sequence reveals differentially expressed genes affecting the crested trait of Wumeng crested chicken.

Poult Sci 2021 Jun 26;100(9):101357. Epub 2021 Jun 26.

Agriculture and Rural Bureau of Huaxi District, Guiyang City, Guizhou Province 550025, China.

Wumeng crested chicken has a cluster of slender feathers on its head, and the underlying skull region exhibits an obvious tumor-like protrusion. This is the typical skull structure of crested chickens. The associated regulatory genes are located on autosomes and are incompletely dominant. Read More

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Aging induces abnormal accumulation of Aβ in extracellular vesicle and/or intraluminal membrane vesicle-rich fractions in nonhuman primate brain.

Neurobiol Aging 2021 Jul 5;106:268-281. Epub 2021 Jul 5.

Section of Cell Biology and Pathology, Department of Alzheimer's Disease Research, Center for Development of Advanced Medicine for Dementia, Obu, Aichi, Japan; Laboratory of Experimental Animals, Research and Development Management Center, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan; Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki, Japan. Electronic address:

Aβ metabolism in the brain is mediated by endocytosis, one part of the intracellular membrane trafficking system. We previously showed that aging attenuates the interaction of dynein with dynactin, which disrupts the endosomal/lysosomal trafficking pathway involved in Aβ metabolism, resulting in intracellular accumulation of Aβ. Several studies have shown that in Alzheimer's disease (AD), intraneuronal accumulation of Aβ precedes extracellular Aβ depositions. Read More

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Adult-born proopiomelanocortin neurons derived from Rax-expressing precursors mitigate the metabolic effects of congenital hypothalamic proopiomelanocortin deficiency.

Mol Metab 2021 Jul 27:101312. Epub 2021 Jul 27.

Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Tufts Medical Center, 800 Washington St, Boston, MA, 02111, USA.

Objective: Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus are essential regulators of energy balance. Selective loss of POMC production in these cells results in extreme obesity and metabolic comorbidities. While neurogenesis occurs in the adult hypothalamus, it remains uncertain whether functional POMC neurons emerge during adulthood in physiologically significant numbers. Read More

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A 3 generation mouse model of Alzheimer's disease shows early and increased cored plaque pathology composed of wild-type human amyloid β peptide.

J Biol Chem 2021 Jul 27:101004. Epub 2021 Jul 27.

Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Electronic address:

We previously developed single App knock-in mouse models of Alzheimer's disease (AD) harboring the Swedish and Beyreuther/Iberian mutations with or without the Arctic mutation (App and App mice, respectively). These models showed Aβ pathology, neuroinflammation, and cognitive impairment in an age-dependent manner. The former model exhibits extensive pathology as early as 6 months, but is unsuitable for investigating Aβ metabolism and clearance because the Arctic mutation renders Aβ resistant to proteolytic degradation and prone to aggregation. Read More

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Novel relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans.

Mol Nutr Food Res 2021 Jul 30:e2100164. Epub 2021 Jul 30.

Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.

Scope: Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. We have previously shown that carnosine supplementation had positive changes on plasma lipidome. Here, we aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome. Read More

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Recommendations for the Design and Implementation of Virtual Reality for Acquired Brain Injury Rehabilitation: Systematic Review.

J Med Internet Res 2021 Jul 30;23(7):e26344. Epub 2021 Jul 30.

Discipline of Speech Pathology, Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

Background: Virtual reality (VR) is increasingly being used for the assessment and treatment of impairments arising from acquired brain injuries (ABIs) due to perceived benefits over traditional methods. However, no tailored options exist for the design and implementation of VR for ABI rehabilitation and, more specifically, traumatic brain injury (TBI) rehabilitation. In addition, the evidence base lacks systematic reviews of immersive VR use for TBI rehabilitation. Read More

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Design and Synthesis of Novel Spiro Derivatives as Potent and Reversible Monoacylglycerol Lipase (MAGL) Inhibitors: Bioisosteric Transformation from 3-Oxo-3,4-dihydro-2-benzo[][1,4]oxazin-6-yl Moiety.

J Med Chem 2021 Jul 30. Epub 2021 Jul 30.

Research, Takeda Pharmaceutical Co., Ltd., 26-1, Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.

The therapeutic potential of monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases has attracted attention worldwide. However, the availability of reversible-type inhibitor is still limited to clarify the pharmacological effect. Herein, we report the discovery of novel spiro chemical series as potent and reversible MAGL inhibitors with a different binding mode to MAGL using Arg57 and His121. Read More

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Distinct temporal expression of GW182 (TNRC6A) in neurons regulates dendritic arborization.

J Cell Sci 2021 Jul 30. Epub 2021 Jul 30.

Centre for Brain Development and Repair, Institute for Stem Cell Science and Regenerative Medicine (InStem), Bangalore, India.

Precise development of the dendritic architecture is a critical determinant of mature neuronal circuitry. MicroRNA-mediated regulation of protein synthesis plays a crucial role in dendritic morphogenesis but the role of miRISC protein components in this process is less studied. Here, we show an important role of a key miRISC protein GW182 paralog TNRC6A in the regulation of dendritic growth. Read More

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Design and optimization of curcumin loaded nano lipid carrier system using Box-Behnken design.

Biomed Pharmacother 2021 Jul 17;141:111919. Epub 2021 Jul 17.

National Institute of Pharmaceutical Education and Research (NIPER-Guwahati), Sila, Changsari, Kamrup, 781 101 Guwahati, Assam, India. Electronic address:

Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer's disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. Read More

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NU9056, a KAT 5 Inhibitor, Treatment Alleviates Brain Dysfunction by Inhibiting NLRP3 Inflammasome Activation, Affecting Gut Microbiota, and Derived Metabolites in LPS-Treated Mice.

Front Nutr 2021 13;8:701760. Epub 2021 Jul 13.

Department of Anesthesiology, The Second Xiangya Hospital, Central South University, Changsha, China.

The pathogenesis of sepsis-associated encephalopathy (SAE) is complicated, while the efficacy of current treatment technologies is poor. Therefore, the discovery of related targets and the development of new drugs are essential. A mouse model of SAE was constructed by intraperitoneal injection of lipopolysaccharide (LPS). Read More

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Neurovascular Coupling in Development and Disease: Focus on Astrocytes.

Front Cell Dev Biol 2021 12;9:702832. Epub 2021 Jul 12.

Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, OR, United States.

Neurovascular coupling is a crucial mechanism that matches the high energy demand of the brain with a supply of energy substrates from the blood. Signaling within the neurovascular unit is responsible for activity-dependent changes in cerebral blood flow. The strength and reliability of neurovascular coupling form the basis of non-invasive human neuroimaging techniques, including blood oxygen level dependent (BOLD) functional magnetic resonance imaging. Read More

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A novel orally active HDAC6 inhibitor T-518 shows a therapeutic potential for Alzheimer's disease and tauopathy in mice.

Sci Rep 2021 Jul 29;11(1):15423. Epub 2021 Jul 29.

Neuroscience Drug Discovery Unit, Research, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-Higashi 2-chome, Fujisawa, Kanagawa, 251-8555, Japan.

Accumulation of tau protein is a key pathology of age-related neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Those diseases are collectively termed tauopathies. Tau pathology is associated with axonal degeneration because tau binds to microtubules (MTs), a component of axon and regulates their stability. Read More

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Intercellular Arc Signaling Regulates Vasodilation.

J Neurosci 2021 Jul 29. Epub 2021 Jul 29.

Department of Biological Sciences, University of Texas at Dallas, Richardson, Texas 75080

Injury responses require communication between different cell types in the skin. Sensory neurons contribute to inflammation and can secrete signaling molecules that affect non-neuronal cells. Despite the pervasive role of translational regulation in nociception, the contribution of activity-dependent protein synthesis to inflammation is not well understood. Read More

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