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https://www.readbyqxmd.com/read/29331172/blood-phenylalanine-reduction-corrects-cns-dopamine-and-serotonin-deficiencies-and-partially-improves-behavioral-performance-in-adult-phenylketonuric-mice
#1
Shelley R Winn, Tanja Scherer, Beat Thöny, Ming Ying, Aurora Martinez, Sydney Weber, Jacob Raber, Cary O Harding
Central nervous system (CNS) deficiencies of the monoamine neurotransmitters dopamine and serotonin have been implicated in the pathophysiology of neuropsychiatric dysfunction in human phenylketonuria (PKU). In this study, we confirmed the occurrence of brain dopamine and serotonin deficiencies in association with severe behavioral alterations and cognitive impairments in hyperphenylalaninemic C57BL/6-Pahenu2/enu2 mice, a model of human PKU. Phenylalanine-reducing treatments, including either dietary phenylalanine restriction or liver-directed gene therapy, initiated during adulthood were associated with increased brain monoamine content along with improvements in nesting behavior but without a change in the severe cognitive deficits exhibited by these mice...
January 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/29229413/constant-light-environment-suppresses-maturation-and-reduces-complexity-of-new-born-neuron-processes-in-the-hippocampus-and-caudal-nidopallium-of-a-diurnal-corvid-implication-for-impairment-of-the-learning-and-cognitive-performance
#2
S K Tahajjul Taufique, Abhilash Prabhat, Vinod Kumar
Periodic day-night environment shapes the temporal pattern in the behaviour and physiology (e.g. 24-h activity-rest and sleep-wake cycles) and the advanced brain function, such as learning, memory and decision making. In a previous study, we showed the abolition of 24-h rhythm in the activity-rest pattern, and an attenuated cognitive performance in diurnal Indian house crows (Corvus splendens) under constant light (no-night; LL) environment. Present study extended this, and investigated LL-induced effects on the neurogenesis (birth, maturation and neurite complexity of new born neurons) in the hippocampus and caudal nidopallium, the brain regions directly associated with learning and cognition in birds...
December 8, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/29223763/dyrk1a-haploinsufficiency-in-mice-causes-autistic-like-features-and-febrile-seizures
#3
Matthieu Raveau, Atsushi Shimohata, Kenji Amano, Hiroyuki Miyamoto, Kazuhiro Yamakawa
Mutations and copy number variants affecting DYRK1A gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1A are among the most frequent genetic causes of neurodevelopmental disorders including autism spectrum disorder (ASD) associated with microcephaly, febrile seizures and severe speech acquisition delay. Here we developed a mouse model harboring a frame-shift mutation in Dyrk1a resulting in a protein truncation and elimination of its kinase activity site. Dyrk1a+/- mice showed significant impairments in cognition and cognitive flexibility, communicative ultrasonic vocalizations, and social contacts...
December 6, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29221819/cerebellar-alterations-in-a-model-of-down-syndrome-the-role-of-the-dyrk1a-gene
#4
Susana García-Cerro, Verónica Vidal, Sara Lantigua, Maria Teresa Berciano, Miguel Lafarga, Pedro Ramos-Cabrer, Daniel Padro, Noemí Rueda, Carmen Martínez-Cué
Down syndrome (DS) is characterized by a marked reduction in the size of the brain and cerebellum. These changes play an important role in the motor alterations and cognitive disabilities observed in this condition. The Ts65Dn (TS) mouse, the most commonly used model of DS, reflects many DS phenotypes, including alterations in cerebellar morphology. One of the genes that is overexpressed in both individuals with DS and TS mice is DYRK1A/Dyrk1A (dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A), which has been implicated in the altered cerebellar structural and functional phenotypes observed in both populations...
December 5, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29215606/cognitive-and-mood-effects-of-a-nutrient-enriched-breakfast-bar-in-healthy-adults-a-randomised-double-blind-placebo-controlled-parallel-groups-study
#5
David O Kennedy, Emma L Wightman, Joanne Forster, Julie Khan, Crystal F Haskell-Ramsay, Philippa A Jackson
OBJECTIVES: Few previous studies have assessed the effects of concomitant administration of multiple potentially psychoactive nutrients. METHODS: 95 healthy adult participants consumed either a nutrient enriched breakfast bar (containing α-Linolenic acid, l-tyrosine, l-theanine, vitamins, minerals and 21.5 mg of caffeine) or an isocaloric, macronutrient matched control bar for 56 days. Cognitive function and mood were assessed pre-dose and at 40- and 160-min post-dose on the 1st and 56th day of the intervention period...
December 7, 2017: Nutrients
https://www.readbyqxmd.com/read/29209170/noradrenaline-modulates-the-membrane-potential-and-holding-current-of-medial-prefrontal-cortex-pyramidal-neurons-via-%C3%AE-1-adrenergic-receptors-and-hcn-channels
#6
Katarzyna Grzelka, Przemysław Kurowski, Maciej Gawlak, Paweł Szulczyk
The medial prefrontal cortex (mPFC) receives dense noradrenergic projections from the locus coeruleus. Adrenergic innervation of mPFC pyramidal neurons plays an essential role in both physiology (control of memory formation, attention, working memory, and cognitive behavior) and pathophysiology (attention deficit hyperactivity disorder, posttraumatic stress disorder, cognitive deterioration after traumatic brain injury, behavioral changes related to addiction, Alzheimer's disease and depression). The aim of this study was to elucidate the mechanism responsible for adrenergic receptor-mediated control of the resting membrane potential in layer V mPFC pyramidal neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29200112/epidemiology-treatment-and-complications-of-central-nervous-system-metastases
#7
Amy A Pruitt
PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29197979/genetic-differences-in-the-aryl-hydrocarbon-receptor-and-cyp1a2-affect-sensitivity-to-developmental-polychlorinated-biphenyl-exposure-in-mice-relevance-to-studies-of-human-neurological-disorders
#8
Kelsey Klinefelter, Molly Kromme Hooven, Chloe Bates, Breann T Colter, Alexandra Dailey, Smitha Krishnan Infante, Izabela Kania-Korwel, Hans-Joachim Lehmler, Alejandro López-Juárez, Clare Pickering Ludwig, Christine Perdan Curran
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with newly discovered sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but highly exposed adults reportedly have an increased risk of Parkinson's disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction...
December 2, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/29179176/neurons-erythrocytes-and-beyond-the-diverse-functions-of-chorein
#9
Florian Lang, Lisann Pelzl, Ludger Schöls, Andreas Hermann, Michael Föller, Tilman E Schäffer, Christos Stournaras
Chorea-acanthocytosis (ChAc), a neurodegenerative disease, results from loss-of-function-mutations of the chorein-encoding gene VPS13A. Affected patients suffer from a progressive movement disorder including chorea, parkinsonism, dystonia, tongue protrusion, dysarthria, dysphagia, tongue and lip biting, gait impairment, progressive distal muscle wasting, weakness, epileptic seizures, cognitive impairment, and behavioral changes. Those pathologies may be paralleled by erythrocyte acanthocytosis. Chorein supports activation of phosphoinositide-3-kinase (PI3K)-p85-subunit with subsequent up-regulation of ras-related C3 botulinum toxin substrate 1 (Rac1) activity, p21 protein-activated kinase 1 (PAK1) phosphorylation, and activation of several tyrosine kinases...
November 28, 2017: Neuro-Signals
https://www.readbyqxmd.com/read/29168741/dose-dependent-effects-of-oral-tyrosine-administration-on-plasma-tyrosine-levels-and-cognition-in-aging
#10
Ondine van de Rest, Mirjam Bloemendaal, Rianne de Heus, Esther Aarts
The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150, or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210, and 240 min after tyrosine intake...
November 23, 2017: Nutrients
https://www.readbyqxmd.com/read/29133763/effects-of-melatonin-levels-on-neurotoxicity-of-the-medial-prefrontal-cortex-in-a-rat-model-of-parkinson-s-disease
#11
Yan Li, Shu-Mei Wang, Lei Guo, Jian Zhu, Ying Wang, Lei Li, Yan-Xin Zhao
BACKGROUND: Damage of the medial prefrontal cortex (mPFC) results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson's disease (PD). Since the course of mPFC damage is still unclear, our study aimed to investigate the effects of melatonin (MT) on neurotoxicity in the mPFC of a rat model of PD. METHODS: One hundred and fifty-four normal, male Wistar rats were randomly divided into the following five groups: normal + normal saline (NS), normal + 6-hydroxydopamine (6-OHDA), sham pinealectomy (PX) + 6-OHDA, PX + 6-OHDA, and MT + 6-OHDA...
November 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/29129676/exercise-enhances-cognitive-function-and-neurotrophin-expression-in-the-hippocampus-accompanied-by-changes-in-epigenetic-programming-in-senescence-accelerated-mice
#12
Hiroshi Maejima, Naohiko Kanemura, Takanori Kokubun, Kenji Murata, Kiyomi Takayanagi
Aerobic exercise is known to increase expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the hippocampus and to improve cognitive function. Exercise exerts neuroprotective effects in the hippocampus by inducing epigenetic changes, which play crucial roles in aging and neurodegenerative diseases. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29122458/adult-onset-leukoencephalopathy-with-axonal-spheroids-and-pigmented-glia-alsp-integrating-the-literature-on-hereditary-diffuse-leukoencephalopathy-with-spheroids-hdls-and-pigmentary-orthochromatic-leukodystrophy-pold
#13
REVIEW
Scott J Adams, Andrew Kirk, Roland N Auer
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a progressive degenerative white matter disorder. ALSP was previously recognized as two distinct entities, hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD). However, recent identification of mutations in the tyrosine kinase domain of the colony stimulating factor 1 receptor (CSF1R) gene, which regulates mononuclear cell lineages including microglia, have provided genetic and mechanistic evidence that POLD and HDLS should be regarded as a single clinicopathologic entity...
November 6, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29116812/x-ray-characterization-and-structure-based-optimization-of-striatal-enriched-protein-tyrosine-phosphatase-inhibitors
#14
Michael R Witten, Lisa Wissler, Melanie Snow, Stefan Geschwindner, Jon A Read, Nicholas J Brandon, Angus C Nairn, Paul J Lombroso, Helena Käck, Jonathan A Ellman
Excessive activity of striatal-enriched protein tyrosine phosphatase (STEP) in the brain has been detected in numerous neuropsychiatric disorders including Alzheimer's disease. Notably, knockdown of STEP in an Alzheimer mouse model effected an increase in the phosphorylation levels of downstream STEP substrates and a significant reversal in the observed cognitive and memory deficits. These data point to the promising potential of STEP as a target for drug discovery in Alzheimer's treatment. We previously reported a substrate-based approach to the development of low molecular weight STEP inhibitors with Ki values as low as 7...
November 8, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29114064/sorla-attenuates-epha4-signaling-and-amyloid-%C3%AE-induced-neurodegeneration
#15
Timothy Y Huang, Yingjun Zhao, Lu-Lin Jiang, Xiaoguang Li, Yan Liu, Yu Sun, Juan C Piña-Crespo, Bing Zhu, Eliezer Masliah, Thomas E Willnow, Elena B Pasquale, Huaxi Xu
Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer's disease (AD). Although SORLA is known to regulate trafficking of the amyloid β (Aβ) precursor protein to decrease levels of proteotoxic Aβ oligomers, whether SORLA can counteract synaptic dysfunction induced by Aβ oligomers remains unclear. Here, we show that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand-induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons...
November 7, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29111458/low-functional-programming-of-the-creb-bdnf-trkb-pathway-mediates-cognitive-impairment-in-male-offspring-after-prenatal-dexamethasone-exposure
#16
Wanting Dong, Dan Xu, Zewen Hu, Xia He, Zijing Guo, Zhexiao Jiao, Ying Yu, Hui Wang
Adverse intrauterine environments can increase susceptibility to neuropsychiatric diseases that are related to cognitive impairment. In this study, we observed the cognitive impairment of male offspring rats after prenatal dexamethasone exposure (PDE) and explored the associated intrauterine programming mechanism. Pregnant Wistar rats were subcutaneously injected with 0.2mg/kgd dexamethasone from gestational day 9 (GD9) to GD20. A cohort of the pregnant rat group was sacrificed on GD20, and the male fetal rats were collected...
October 27, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29111184/neuron-protective-effect-of-subanesthestic-dosage-ketamine-on-mice-of-parkinson-s-disease
#17
Jun-Chao Fan, Jun-Jie Song, Ying Wang, Ying Chen, Dao-Xian Hong
OBJECTIVE: To discuss the neuron-protective effect and possible mechanism of subanesthestic-dosage ketamine on Parkinson's disease mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. METHODS: A total of 30 mice were divided equally into three groups, model control group (MC group), ketamine treatment group (KT group), and blank control group (BC group), respectively. The Parkinson's disease mice of MC group and KT groups were established by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (20 mg/kg/d), while mice in KT group were treated by intraperitoneal injection of subanesthestic-dosage ketamine (8 mg/kg)...
October 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29107098/corticosteroid-induced-dendrite-loss-and-behavioral-deficiencies-can-be-blocked-by-activation-of-abl2-arg-kinase
#18
Lauren P Shapiro, Mitchell H Omar, Anthony J Koleske, Shannon L Gourley
Stressor exposure induces neuronal remodeling in specific brain regions. Given the persistence of stress-related illnesses, key next steps in determining the contributions of neural structure to mental health are to identify cell types that fail to recover from stressor exposure and to identify "trigger points" and molecular underpinnings of stress-related neural degeneration. We evaluated dendrite arbor structure on hippocampal CA1 pyramidal neurons before, during, and following prolonged exposure to one key mediator of the stress response - corticosterone (cortisol in humans)...
October 26, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29076421/seizures-and-anticonvulsants-in-brain-tumours-frequency-mechanisms-and-anti-epileptic-management
#19
Charles Vecht, Louis Royer-Perron, Caroline Houillier, Gilles Huberfeld
In cancer, epilepsy can be the manifestation of a primary brain tumour, metastatic disease, vascular or surgical complications, opportunistic infection or secondary to anti-tumour therapy. Seizures are frequently the first symptom of a brain tumour. The epilepsy is related to elevated extracellular glutamate stimulating NMDA- and AMPA-receptors and to the formation of D-2HG which resembles glutamate in IDH1 mutated gliomas. Epilepsy as presenting sign is associated with a longer survival in low- and high- grade gliomas, particularly with the IDH1 mutation...
October 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29057453/5-ht1f-receptor-mediated-mitochondrial-biogenesis-for-the-treatment-of-parkinson-s-disease
#20
Natalie E Scholpa, Mary K Lynn, Daniel Corum, Heather A Boger, Rick G Schnellmann
BACKGROUND AND PURPOSE: Parkinson's disease is characterized by progressive decline in motor function due to degeneration of nigrostriatal dopaminergic neurons, as well as other deficits including cognitive impairment and behavioral abnormalities. Mitochondrial dysfunction, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, is implicated in the pathophysiology of Parkinson's disease. Using the 5-HT1F receptor agonist LY344864, a known inducer of mitochondrial biogenesis (MB), this study investigated the therapeutic efficacy of stimulating MB on dopaminergic neuron loss in a mouse model of Parkinson's disease...
October 22, 2017: British Journal of Pharmacology
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