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https://www.readbyqxmd.com/read/28527032/methylone-and-mdpv-activate-autophagy-in-human-dopaminergic-sh-sy5y-cells-a-new-insight-into-the-context-of-%C3%AE-keto-amphetamines-related-neurotoxicity
#1
Maria João Valente, Cristina Amaral, Georgina Correia-da-Silva, José Alberto Duarte, Maria de Lourdes Bastos, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Autophagy has an essential role in neuronal homeostasis and its dysregulation has been recently linked to neurotoxic effects of a growing list of psychoactive drugs, including amphetamines. However, the role of autophagy in β-keto amphetamine (β-KA) designer drugs-induced neurotoxicity has hitherto not been investigated. In the present study, we show that two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), elicit morphological changes consistent with autophagy and neurodegeneration, including formation of autophagic vacuoles and neurite retraction in dopaminergic SH-SY5Y cells...
May 19, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28526930/micrornas-in-parkinson-s-disease
#2
REVIEW
Abhishek Singh, Dwaipayan Sen
Parkinson's disease is the second most common neurodegenerative disease commonly affecting the older population. Loss of dopaminergic neurons in the substantia nigra of brain leads to impairment of motor activities as well as cognitive defects. There are many underlying causes to this disease, both genetic and epigenetic, which are yet to be fully explored. Non-coding RNAs are significant part of our genome and are involved in various cellular processes. MicroRNAs, which are small non-coding RNAs having 20-22 nucleotides, are involved in many underlying mechanisms of pathogenesis of several neurodegenerative diseases including Parkinson's...
May 19, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28525574/a-schizophrenia-related-deletion-leads-to-kcnq2-dependent-abnormal-dopaminergic-modulation-of-prefrontal-cortical-interneuron-activity
#3
Se Joon Choi, Jun Mukai, Mirna Kvajo, Bin Xu, Anastasia Diamantopoulou, Pothitos M Pitychoutis, Bin Gou, Joseph A Gogos, Hui Zhang
Altered prefrontal cortex function is implicated in schizophrenia (SCZ) pathophysiology and could arise from imbalance between excitation and inhibition (E/I) in local circuits. It remains unclear whether and how such imbalances relate to genetic etiologies. We used a mouse model of the SCZ-predisposing 22q11.2 deletion (Df(16)A+/- mice) to evaluate how this genetic lesion affects the excitability of layer V prefrontal pyramidal neurons and its modulation by dopamine (DA). Df(16)A+/- mice have normal balance between E/I at baseline but are unable to maintain it upon dopaminergic challenge...
May 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28521299/isradipine-attenuates-mptp-induced-dopamine-neuron-degeneration-by-inhibiting-up-regulation-of-l-type-calcium-channels-and-iron-accumulation-in-the-substantia-nigra-of-mice
#4
Qi-Min Wang, Yu-Yu Xu, Shang Liu, Ze-Gang Ma
The aim of this study is to investigate the effects of L-type calcium channels (LTCCs) on MPTP-induced dopamine (DA) neuron degeneration and iron accumulation in the substantia nigra (SN) of mice. By real-time PCR and western blots, we first quatified expressions of L-type Cav1.2 and Cav1.3 calcium channel α1 subunits in the SN of experimental mice treated with MPTP. We found that the expressions of Cav1.2 and Cav1.3 calcium channel α1 subunits markedly increased after MPTP treatment for 2 and 3 weeks. Secondly, we observed the effects of isradipine, a LTCC antagonist, on MPTP-induced DA neuron degeneration and iron accumulation in the SN...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521136/dopamine-depletion-impairs-bilateral-sensory-processing-in-the-striatum-in-a-pathway-dependent-manner
#5
M Ketzef, G Spigolon, Y Johansson, A Bonito-Oliva, G Fisone, G Silberberg
Parkinson's disease (PD) is a movement disorder caused by the loss of dopaminergic innervation, particularly to the striatum. PD patients often exhibit sensory impairments, yet the underlying network mechanisms are unknown. Here we examined how dopamine (DA) depletion affects sensory processing in the mouse striatum. We used the optopatcher for online identification of direct and indirect pathway projection neurons (MSNs) during in vivo whole-cell recordings. In control mice, MSNs encoded the laterality of sensory inputs with larger and earlier responses to contralateral than ipsilateral whisker deflection...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#6
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28520507/gold-nanoparticles-enhance-the-differentiation-of-embryonic-stem-cells-into-dopaminergic-neurons-via-mtor-p70s6k-pathway
#7
Min Wei, Song Li, Zhaofei Yang, Wei Zheng, Weidong Le
AIM: This study aimed to investigate the effect of gold nanoparticles (AuNPs) on differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DA) neurons and explore the possible underlying molecular mechanisms. MATERIALS & METHODS: The efficiency of AuNPs on DA neuron differentiation was evaluated by observing fluorescence in TH promoter-engineered GFP-reporter ESCs, western blot and real-time PCR. The possible signal pathway was determined by western blot...
May 18, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28511934/repeated-manganese-administration-produced-abnormal-expression-of-circadian-clock-genes-in-the-hypothalamus-and-liver-of-rats
#8
Huan Li, Ximin Fan, Ying Luo, Sheng Song, Jie Liu, Qiyuan Fan
Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment like Parkinson's disease (PD), and is called as Manganism. Circadian disruption is a non-motor symptom found in PD and Manganism. Clock genes are essential to drive and maintain circadian rhythm, but little is known about Mn exposure on circadian clock genes expression. Both the brain and liver are targets of Mn, we hypothesize that repeated Mn administration could affect clock gene expression in the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally injected Mn(2+)1mg and 5mg /kg as MnCl2•4H2O, every other day for 30 days...
May 13, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28511367/neurobehavioural-changes-in-a-hemiparkinsonian-rat-model-induced-by-rotenone
#9
REVIEW
Sukala Puthuparambil Maniyath, Narayanan Solaiappan, Muthusamy Rathinasamy
INTRODUCTION: Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28511006/novel-focused-ultrasound-gene-therapy-approach-noninvasively-restores-dopaminergic-neuron-function-in-a-rat-parkinson-s-disease-model
#10
Brian P Mead, Namho Kim, G Wilson Miller, David Hodges, Panagiotis Mastorakos, Alexander L Klibanov, James W Mandell, Jay Hirsh, Jung Soo Suk, Justin Hanes, Richard J Price
Therapies capable of decelerating, or perhaps even halting, neurodegeneration in Parkinson's disease (PD) remain elusive. Clinical trials of PD gene therapy testing the delivery of neurotrophic factors, such as the glial cell-line derived neurotrophic factor (GDNF), have been largely ineffective due to poor vector distribution throughout the diseased regions in the brain. In addition, current delivery strategies involve invasive procedures that obviate the inclusion of early stage patients who are most likely to benefit from GDNF-based gene therapy...
May 18, 2017: Nano Letters
https://www.readbyqxmd.com/read/28508315/trpc-channels-and-parkinson-s-disease
#11
Pramod Sukumaran, Yuyang Sun, Anne Schaar, Senthil Selvaraj, Brij B Singh
Parkinson's disease (PD) is a common neurodegenerative disorder, which involves degeneration of dopaminergic neurons that are present in the substantia nigra pars compacta (SNpc) region. Many factors have been identified that could lead to Parkinson's disease; however, almost all of them are directly or indirectly dependent on Ca(2+) signaling. Importantly, though disturbances in Ca(2+) homeostasis have been implicated in Parkinson's disease and other neuronal diseases, the identity of the calcium channel remains elusive...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28507584/effects-of-adenosine-receptor-antagonists-in-mptp-mouse-model-of-parkinson-s-disease-mitochondrial-dna-integrity
#12
Soha S Essawy, Mona Kamal Tawfik, Horya Erfan Korayem
INTRODUCTION: In Parkinson's disease (PD), compelling data indicate a functional link between adenosine/dopamine receptors and the progression of the neurodegenerative process. The present study was carried out to evaluate the effect of the non-selective adenosine receptor (ADR) antagonist caffeine, as well as the selective antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), an ADRsA1 antagonist, and ((E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1H-purine-2,6-dione) (KW-6002), an ADRsA2A antagonist, on the prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in mice...
April 1, 2017: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/28507529/parkinson-disease-an-evolutionary-perspective
#13
Pedro J Garcia-Ruiz, Alberto J Espay
There are two central premises to this evolutionary view of Parkinson disease (PD). First, PD is a specific human disease. Second, the prevalence of PD has increased over the course of human history. Several lines of evidence may explain why PD appears to be restricted to the human species. The major manifestations of PD are the consequence of degeneration in the dopamine-synthesizing neurons of the mesostriatal neuronal pathway. It is of note the enormous expansion of the human dopamine mesencephalic neurons onto the striatum compared with other mammals...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28507507/pink1-parkin-dependent-mitochondrial-surveillance-from-pleiotropy-to-parkinson-s-disease
#14
REVIEW
Francois Mouton-Liger, Maxime Jacoupy, Jean-Christophe Corvol, Olga Corti
Parkinson's disease (PD) is one of the most frequent neurodegenerative disease caused by the preferential, progressive degeneration of the dopaminergic (DA) neurons of the substantia nigra (SN) pars compacta. PD is characterized by a multifaceted pathological process involving protein misfolding, mitochondrial dysfunction, neuroinflammation and metabolism deregulation. The molecular mechanisms governing the complex interplay between the different facets of this process are still unknown. PARK2/Parkin and PARK6/PINK1, two genes responsible for familial forms of PD, act as a ubiquitous core signaling pathway, coupling mitochondrial stress to mitochondrial surveillance, by regulating mitochondrial dynamics, the removal of damaged mitochondrial components by mitochondria-derived vesicles, mitophagy, and mitochondrial biogenesis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28507136/ocd-candidate-gene-slc1a1-eaat3-impacts-basal-ganglia-mediated-activity-and-stereotypic-behavior
#15
Isaac D Zike, Muhammad O Chohan, Jared M Kopelman, Emily N Krasnow, Daniel Flicker, Katherine M Nautiyal, Michael Bubser, Christoph Kellendonk, Carrie K Jones, Gregg Stanwood, Kenji Fransis Tanaka, Holly Moore, Susanne E Ahmari, Jeremy Veenstra-VanderWeele
Obsessive-compulsive disorder (OCD) is a chronic, disabling condition with inadequate treatment options that leave most patients with substantial residual symptoms. Structural, neurochemical, and behavioral findings point to a significant role for basal ganglia circuits and for the glutamate system in OCD. Genetic linkage and association studies in OCD point to SLC1A1, which encodes the neuronal glutamate/aspartate/cysteine transporter excitatory amino acid transporter 3 (EAAT3)/excitatory amino acid transporter 1 (EAAC1)...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28507134/dopaminergic-modulation-of-basal-ganglia-output-through-coupled-excitation-inhibition
#16
Agata Budzillo, Alison Duffy, Kimberly E Miller, Adrienne L Fairhall, David J Perkel
Learning and maintenance of skilled movements require exploration of motor space and selection of appropriate actions. Vocal learning and social context-dependent plasticity in songbirds depend on a basal ganglia circuit, which actively generates vocal variability. Dopamine in the basal ganglia reduces trial-to-trial neural variability when the bird engages in courtship song. Here, we present evidence for a unique, tonically active, excitatory interneuron in the songbird basal ganglia that makes strong synaptic connections onto output pallidal neurons, often linked in time with inhibitory events...
May 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28506618/the-ptz-kindling-mouse-model-of-epilepsy-exhibits-exploratory-drive-deficits-and-aberrant-vta-dopamine-neuron-activity-in-both-familiar-and-novel-space
#17
Mahboubeh Ahmadi, Jean-Philippe Dufour, Erich Seifritz, Javad Mirnajafi-Zadeh, Bechara J Saab
Recurrent seizures that define epilepsy are often accompanied by psychosocial problems and cognitive deficits with incompletely understood aetiology. We therefore used the pentylenetetrazol (PTZ) kindling model of epilepsy in mice to examine potential seizure-associated neuropathologies, focusing on motivation, memory and novel-environment-induced activation of midbrain dopaminergic neurons. In addition to recurrent seizures, we found that PTZ kindling led to a strong suppression of novelty-driven exploration while largely sparing fear-driven exploration...
May 12, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28505596/engineered-hydrogels-increase-the-post-transplantation-survival-of-encapsulated-hesc-derived-midbrain-dopaminergic-neurons
#18
Maroof M Adil, Tandis Vazin, Badriprasad Ananthanarayanan, Gonçalo M C Rodrigues, Antara T Rao, Rishikesh U Kulkarni, Evan W Miller, Sanjay Kumar, David V Schaffer
Cell replacement therapies have broad biomedical potential; however, low cell survival and poor functional integration post-transplantation are major hurdles that hamper clinical benefit. For example, following striatal transplantation of midbrain dopaminergic (mDA) neurons for the treatment of Parkinson's disease (PD), only 1-5% of the neurons typically survive in preclinical models and in clinical trials. In general, resource-intensive generation and implantation of larger numbers of cells are used to compensate for the low post-transplantation cell-survival...
May 5, 2017: Biomaterials
https://www.readbyqxmd.com/read/28504367/neuroprotective-natural-products-for-the-treatment-of-parkinson-s-disease-by-targeting-the-autophagy-lysosome-pathway-a-systematic-review
#19
REVIEW
Zi-Ying Wang, Jing-Yi Liu, Chuan-Bin Yang, Sandeep Malampati, Ying-Yu Huang, Mei-Xiang Li, Min Li, Ju-Xian Song
The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment...
May 15, 2017: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/28504254/neural-circuits-for-long-term-water-reward-memory-processing-in-thirsty-drosophila
#20
Wei-Huan Shyu, Tai-Hsiang Chiu, Meng-Hsuan Chiang, Yu-Chin Cheng, Ya-Lun Tsai, Tsai-Feng Fu, Tony Wu, Chia-Lin Wu
The intake of water is important for the survival of all animals and drinking water can be used as a reward in thirsty animals. Here we found that thirsty Drosophila melanogaster can associate drinking water with an odour to form a protein-synthesis-dependent water-reward long-term memory (LTM). Furthermore, we found that the reinforcement of LTM requires water-responsive dopaminergic neurons projecting to the restricted region of mushroom body (MB) β' lobe, which are different from the neurons required for the reinforcement of learning and short-term memory (STM)...
May 15, 2017: Nature Communications
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