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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/kg.d 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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28991675/sodium-butyrate-exerts-protective-effect-against-parkinson-s-disease-in-mice-via-stimulation-of-glucagon-like-peptide-1
#11
Jiaming Liu, Fangyan Wang, Suzhi Liu, Jimei Du, Xuezhen Hu, Jiaojiao Xiong, Renchi Fang, Wenqian Chen, Jing Sun
Sodium butyrate (NaB) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of NaB in a mouse model of Parkinson's disease (PD). A mouse was intraperitoneally treated with MPTP (30mg/kg) for 7 consecutive days to induce PD model and NaB (200mg/kg) was intragastrically treated for 3weeks. The behavioral tests were then conducted. Dopaminergic degeneration was evaluated by western blot and immunohistochemistry of tyrosine hydroxylase (TH) in the SN...
October 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28988132/ferulic-acid-attenuates-diabetes-induced-cognitive-impairment-in-rats-via-regulation-of-ptp1b-and-insulin-signaling-pathway
#12
Hao Wang, Xiaoxu Sun, Ning Zhang, Zhouye Ji, Zhanqiang Ma, Qiang Fu, Rong Qu, Shiping Ma
Cognitive impairment has been recognized as a typical characteristic of neurodegenerative disease in diabetes mellitus (DM) and this cognitive dysfunction may be a risk factor for Alzheimer's disease (AD). Ferulic acid, a phenolic compound commonly found in a range of plants, has emerged various properties including anti-inflammatory and neuroprotective effects. In the present study, the protective activities and relevant mechanisms of ferulic acid were evaluated in diabetic rats with cognitive deficits, which were induced by a high-glucose-fat (HGF) diet and low dose of streptozotocin (STZ)...
December 1, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28981273/chronic-dietary-selenomethionine-exposure-induces-oxidative-stress-dopaminergic-dysfunction-and-cognitive-impairment-in-adult-zebrafish-danio-rerio
#13
Mohammad Naderi, Arash Salahinejad, Ankur Jamwal, Douglas P Chivers, Som Niyogi
The present study was designed to investigate the effects of chronic dietary exposure to selenium (Se) on zebrafish cognition and also to elucidate possible mechanism(s) by which Se exerts its neurotoxicity. To this end, adult zebrafish were exposed to different concentrations of dietary l-selenomethionine (control, 2.3, 9.7, 32.5, or 57.7 μg Se/g dry weight) for 30 days. Cognitive performance of fish was tested using a latent learning paradigm in a complex maze. In addition, we also evaluated oxidative stress biomarkers and the expression of genes involved in dopaminergic neurotransmission in the zebrafish brain...
November 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28970069/age-related-changes-in-the-metabolic-profiles-of-rat-hippocampus-medial-prefrontal-cortex-and-striatum
#14
Lina Wati Durani, Hamizah Shahirah Hamezah, Nor Faeizah Ibrahim, Daijiro Yanagisawa, Suzana Makpol, Hanafi Ahmad Damanhuri, Ikuo Tooyama
We have recently shown that age-dependent regional brain atrophy and lateral ventricle expansion may be linked with impaired cognitive and locomotor functions. However, metabolic profile transformation in different brain regions during aging is unknown. This study examined metabolic changes in the hippocampus, medial prefrontal cortex (mPFC) and striatum of middle- and late-aged Sprague-Dawley rats using ultrahigh performance liquid chromatography coupled with high-resolution accurate mass-orbitrap tandem mass spectrometry...
November 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28963530/super-resolution-microscopy-reveals-functional-organization-of-dopamine-transporters-into-cholesterol-and-neuronal-activity-dependent-nanodomains
#15
Troels Rahbek-Clemmensen, Matthew D Lycas, Simon Erlendsson, Jacob Eriksen, Mia Apuschkin, Frederik Vilhardt, Trine N Jørgensen, Freja H Hansen, Ulrik Gether
Dopamine regulates reward, cognition, and locomotor functions. By mediating rapid reuptake of extracellular dopamine, the dopamine transporter is critical for spatiotemporal control of dopaminergic neurotransmission. Here, we use super-resolution imaging to show that the dopamine transporter is dynamically sequestrated into cholesterol-dependent nanodomains in the plasma membrane of presynaptic varicosities and neuronal projections of dopaminergic neurons. Stochastic optical reconstruction microscopy reveals irregular dopamine transporter nanodomains (∼70 nm mean diameter) that were highly sensitive to cholesterol depletion...
September 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28935605/pyridoxine-improves-hippocampal-cognitive-function-via-increases-of-serotonin-turnover-and-tyrosine-hydroxylase-and-its-association-with-cb1-cannabinoid-receptor-interacting-protein-and-the-cb1-cannabinoid-receptor-pathway
#16
Hyo Young Jung, Dae Won Kim, Sung Min Nam, Jong Whi Kim, Jin Young Chung, Moo-Ho Won, Je Kyung Seong, Yeo Sung Yoon, Dae Young Yoo, In Koo Hwang
BACKGROUND: In the present study, we investigated the effects of pyridoxine on hippocampal functions and changes in protein profiles based on the proteomic approach. METHODS: Eight-week-old mice received intraperitoneal injections of physiological saline (vehicle) or 350mg/kg pyridoxine twice a day for 21days. RESULTS: Phosphoglycerate mutase 1 was up-regulated, while CB1 cannabinoid receptor-interacting protein 1 (CRIP1) was down-regulated, in the pyridoxine-treated group...
December 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28919515/trace-amine-associated-receptor-1-regulation-of-methamphetamine-induced-neurotoxicity
#17
Nicholas B Miner, Josh S Elmore, Michael H Baumann, Tamara J Phillips, Aaron Janowsky
Trace amine-associated receptor 1 (TAAR1) is activated by methamphetamine (MA) and modulates dopaminergic (DA) function. Although DA dysregulation is the hallmark of MA-induced neurotoxicity leading to behavioral and cognitive deficits, the intermediary role of TAAR1 has yet to be characterized. To investigate TAAR1 regulation of MA-induced neurotoxicity, Taar1 transgenic knock-out (KO) and wildtype (WT) mice were administered saline or a neurotoxic regimen of 4 i.p. injections, 2h apart, of MA (2.5, 5, or 10mg/kg)...
December 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28895489/effects-of-mild-running-on-substantia-nigra-during-early-neurodegeneration
#18
Michael F Almeida, Carolliny M Silva, Rodrigo S Chaves, Nathan C R Lima, Renato S Almeida, Karla P Melo, Marilene Demasi, Tiago Fernandes, Edilamar M Oliveira, Luis E S Netto, Sandra M Cardoso, Merari F R Ferrari
Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level...
September 12, 2017: Journal of Sports Sciences
https://www.readbyqxmd.com/read/28887803/psychosis-in-spinocerebellar-ataxias-a-case-series-and-study-of-tyrosine-hydroxylase-in-substantia-nigra
#19
Katherine W Turk, Margaret E Flanagan, Samuel Josephson, C Dirk Keene, Suman Jayadev, Thomas D Bird
Spinocerebellar ataxias are a genetically heterogeneous group of degenerative diseases typically characterized by progressive ataxia and to various degrees, neuropathy, amyotrophy, and ocular abnormalities. There is increasing evidence for non-motor manifestations associated with cerebellar syndromes including cognitive and psychiatric features. We studied a retrospective clinical case series of eight subjects with spinocerebellar ataxias (SCAs) 2, 3, 7, and 17, all displaying features of psychosis, and also measured tyrosine hydroxylase (TH) staining of the substantia nigra (SN) at autopsy, among four of the subjects...
September 8, 2017: Cerebellum
https://www.readbyqxmd.com/read/28842826/environmental-enrichment-reverses-tyrosine-kinase-inhibitor-mediated-impairment-through-bdnf-trkb-pathway
#20
Harkaitz Bengoetxea, Irantzu Rico-Barrio, Naiara Ortuzar, Ane Murueta-Goyena, José V Lafuente
Exposure to an enriched environment (EE) has neuroprotective benefits and improves recovery from brain injury due to, among other, increased neurotrophic factor expression. Through these neurotrophins, important cortical and hippocampal changes occur. Vandetanib acts as a tyrosine kinase inhibitor of cell receptors, among others, the vascular endothelial growth factor receptor (VEGFR). Our aim was to investigate the effectiveness of EE counteracting cognitive and cellular effects after tyrosine kinase receptor blockade...
August 25, 2017: Molecular Neurobiology
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