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https://www.readbyqxmd.com/read/28633499/lateralized-basal-ganglia-vulnerability-to-pesticide-exposure-in-asymptomatic-agricultural-workers
#1
Mechelle M Lewis, Nicholas W Sterling, Guangwei Du, Eun-Young Lee, Grace Shyu, Michael Goldenberg, Thomas Allen, Christy Stetter, Lan Kong, Shedra Amy Snipes, Byron C Jones, Honglei Chen, Richard B Mailman, Xuemei Huang
Background: Pesticide exposure is linked to Parkinson's disease (PD), a neurodegenerative disorder marked by dopamine cell loss in the substantia nigra of the basal ganglia (BG) that often presents asymmetrically. We previously reported that pesticide-exposed agricultural workers (AW) have nigral diffusion tensor (DTI) changes. The current study sought to confirm this finding, and explore its hemisphere and regional specificity within BG structures using an independent sample population...
June 19, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28631520/striatal-changes-underlie-mpep-mediated-suppression-of-the-acquisition-and-expression-of-pramipexole-induced-place-preference-in-an-alpha-synuclein-rat-model-of-parkinson-s-disease
#2
Simon Loiodice, Portia McGhan, Vitalina Gryshkova, Renaud Fleurance, David Dardou, Aziz Hafidi, Andre Nogueira da Costa, Franck Durif
Impulsive-compulsive disorders in Parkinson's disease patients have been described as behavioural or substance addictions including pathological gambling or compulsive medication use of dopamine replacement therapy. A substantial gap remains in the understanding of these disorders. We previously demonstrated that the rewarding effect of the D2/D3 agonist pramipexole was enhanced after repeated exposure to L-dopa and alpha-synuclein mediated dopaminergic nigral loss with specific transcriptional signatures suggesting a key involvement of the glutamatergic pathway...
June 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28617379/-immunohistochemical-characteristics-of-the-substantia-nigra-neurons-of-the-human
#3
D E Korzhevskii, I P Grigor'ev, E G Sukhorukova, V V Gusel'nikova
AIM: To determine the cytochemical characteristics of unchanged neurons of the human substantia nigra using a wide range of immunocytochemical markers some of which (glutamate decarboxylase-65, PGP 9.5, non-phosphorylated neurofilament proteins, alpa-tubulin) have never been used for study of human dopaminergic neurons. MATERIAL AND METHODS: Fragments of human midbrain (17 men and women, aged from 28 to 78 years) from the archives of the Department of General and Specific Morphology of the Institute of Experimental Medicine were used...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28597409/progression-and-persistence-of-neurotoxicity-induced-by-mdma-in-dopaminergic-regions-of-the-mouse-brain-and-association-with-noradrenergic-gabaergic-and-serotonergic-damage
#4
Giulia Costa, Micaela Morelli, Nicola Simola
The amphetamine-related drug 3,4-methylenedioxymethamphetamine (MDMA) is known to induce neurotoxic damage in dopaminergic regions of the mouse brain. In order to characterize how the number of administrations influenced the severity of MDMA-induced dopaminergic damage and to describe the localization and persistence of this damage, we evaluated the changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) in different regions of the mouse brain. Moreover, we investigated whether dopaminergic damage was associated with noradrenergic, GABAergic, and serotonergic damage, by evaluating the changes in noradrenaline transporter (NET), glutamic acid decarboxylase-67 (GAD-67), and serotonin transporter (SERT)...
June 9, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28595911/manganese-exposure-exacerbates-progressive-motor-deficits-and-neurodegeneration-in-the-mitopark-mouse-model-of-parkinson-s-disease-relevance-to-gene-and-environment-interactions-in-metal-neurotoxicity
#5
Langley Monica R, Ghaisas Shivani, Ay Muhammet, Luo Jie, Palanisamy Bharathi N, Jin Huajun, Anantharam Vellareddy, Arthi Kanthasamy, Anumantha G Kanthasamy
Parkinson's disease (PD) is now recognized as a neurodegenerative condition caused by a complex interplay of genetic and environmental influences. Chronic manganese (Mn) exposure has been implicated in the development of PD. Since mitochondrial dysfunction is associated with PD pathology as well as Mn neurotoxicity, we investigated whether Mn exposure augments mitochondrial dysfunction and neurodegeneration in the nigrostriatal dopaminergic system using a newly available mitochondrially defective transgenic mouse model of PD, the MitoPark mouse...
June 5, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28580639/mesenchymal-stem-cells-stabilize-axonal-transports-for-autophagic-clearance-of-%C3%AE-synuclein-in-parkinsonian-models
#6
Se Hee Oh, Seok Cheol Lee, Dong Yeol Kim, Ha Na Kim, Jin Young Shin, Byoung Seok Ye, Phil Hyu Lee
Genome-wide association studies have identified two loci, SNCA and the microtubule (MT)-associated protein tau, as common risk factors for Parkinson's disease (PD). Specifically, α-synuclein directly destabilizes MT via tau phosphorylation and induces axonal transport deficits that are the primary events leading to an abnormal accumulation of α-synuclein that causes nigral dopaminergic cell loss. In the present study, we demonstrated that mesenchymal stem cells (MSCs) could modulate cytoskeletal networks and trafficking to exert neuroprotective properties in wild-type or A53T α-synuclein overexpressing cells and mice...
June 5, 2017: Stem Cells
https://www.readbyqxmd.com/read/28560490/laser-capture-microdissection-protocol-for-gene-expression-analysis-in-the-brain
#7
P Garrido-Gil, P Fernandez-Rodríguez, J Rodríguez-Pallares, Jose L Labandeira-Garcia
Laser capture microdissection (LCM) allows the isolation of specific cell populations from complex tissues that can be then used for gene expression studies. However, there are no reproducible protocols to study RNA in the brain and, particularly, in the substantia nigra. RNA is a very labile biomolecule that is easily degraded during manipulation. LCM studies use low amounts of material and special precautions must be taken to preserve RNA yield and integrity, which are decisive for PCR analysis. The RNA yield and/or integrity can be affected negatively by tissue manipulation, LCM process and RNA extraction...
May 31, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28552073/intrastriatal-injection-of-%C3%AE-synuclein-can-lead-to-widespread-synucleinopathy-independent-of-neuroanatomic-connectivity
#8
Zachary A Sorrentino, Mieu M T Brooks, Vincent Hudson, Nicola J Rutherford, Todd E Golde, Benoit I Giasson, Paramita Chakrabarty
BACKGROUND: Prionoid transmission of α-synuclein (αSyn) aggregates along neuroanatomically connected projections is posited to underlie disease progression in α-synucleinopathies. Here, we specifically wanted to study whether this prionoid progression occurs via direct inter-neuronal transfer and, if so, would intrastriatal injection of αSyn aggregates lead to nigral degeneration. METHODS: To test prionoid transmission of αSyn aggregates along the nigro-striatal pathway, we injected amyloidogenic αSyn aggregates into two different regions of the striatum of adult human wild type αSyn transgenic mice (Line M20) or non-transgenic (NTG) mice and aged for 4 months...
May 29, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28537985/neuroimaging-in-parkinson-s-disease-focus-on-substantia-nigra-and-nigro-striatal-projection
#9
Daniela Frosini, Mirco Cosottini, Duccio Volterrani, Roberto Ceravolo
PURPOSE OF REVIEW: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. RECENT FINDINGS: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation...
May 22, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#10
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/28516282/region-specific-iron-measured-by-mri-as-a-biomarker-for-parkinson-s-disease
#11
REVIEW
Xiaojun Guan, Xiaojun Xu, Minming Zhang
The identification of sensitive and specific biomarkers for Parkinson's disease (PD) poses an important clinical challenge. A potential biomarker for early diagnosis and disease monitoring of PD is region-specific iron. Iron accumulation in the substantia nigra pars compacta is considered a main characteristic of PD. However, questions remain, such as the relationship between nigral iron and clinical indices of PD (motor impairment or disease duration). Further, previous studies have suggested the influence of iron on other nuclei...
May 17, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28507529/parkinson-disease-an-evolutionary-perspective
#12
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/28493825/repetitive-transcranial-magnetic-stimulation-for-treatment-of-lactacystin-induced-parkinsonian-rat-model
#13
Maowen Ba, Guozhao Ma, Chao Ren, Xuwen Sun, Min Kong
The dysfunction of ubiquitin-proteasome system is an important pathogenesis in the neurodegenerative process of Parkinson's disease. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive and potential method in treating Parkinson's disease. To investigate whether rTMS has neuroprotective effects in parkinsonian rat model induced by ubiquitin-proteasome system impairment, we gave rTMS daily for 4 weeks to proteasome inhibitor, lactacystin-induced parkinsonian rat model. Rotational behavior test demonstrated that rTMS obviously reduced apomorphine-induced turning number in parkinsonian rats...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28488766/brief-isoflurane-anesthesia-regulates-striatal-akt-gsk3%C3%AE-signaling-and-ameliorates-motor-deficits-in-a-rat-model-of-early-stage-parkinson-s-disease
#14
Juuso V Leikas, Samuel Kohtala, Wiebke Theilmann, Aaro J Jalkanen, Markus M Forsberg, Tomi Rantamäki
Parkinson's disease (PD) is a progressive neurodegenerative movement disorder primarily affecting the nigrostriatal dopaminergic system. The link between heightened activity of glycogen synthase kinase 3β (GSK3β) and neurodegenerative processes has encouraged investigation into the potential disease modifying effects of novel GSK3β inhibitors in experimental models of PD. Therefore, the intriguing ability of several anesthetics to readily inhibit GSK3β within the cortex and hippocampus led us to investigate the effects of brief isoflurane anesthesia on striatal GSK3β signaling in naïve rats and in a rat model of early-stage PD...
May 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28479587/structure-distribution-and-genetic-profile-of-%C3%AE-synuclein-and-their-potential-clinical-application-in-parkinson-s-disease
#15
Xiaoli Si, Jiali Pu, Baorong Zhang
Parkinson's disease (PD), the second most common neurodegenerative disorder after Alzheimer's disease, is characterized by the loss of nigral dopaminergic neurons. PD leads to a series of clinical symptoms, including motor and non-motor disturbances. α-synuclein, the major component of Lewy bodies, is a hallmark lesion in PD. In this review, we concentrate on presenting the latest research on the structure, distribution, and function of α-synuclein, and its interactions with PD. We also summarize the clinic applications of α-synuclein, which suggest its use as a biomarker, and the latest progress in α-synuclein therapy...
May 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28471847/neuroprotective-effect-of-resveratrol-on-rotenone-treated-c57bl-6-mice
#16
Xiaofei Zhao, Jun Wang, Song Hu, Renping Wang, Yongjun Mao, Junxia Xie
The aim of the present study was to investigate whether resveratrol could reduce nigral iron levels to prevent the degeneration of dopaminergic neurons in the substantia nigra (SN) of C57BL/6 mice induced by rotenone. Parkinson's disease (PD) is an age-related neurodegenerative disorder; elevated iron levels in the SN participate in neuronal death in PD. Resveratrol is a kind of polyphenolic compounds and possess antioxidant, anticancer, and anti-inflammatory biological functions. Although many research groups have investigated the neuroprotective effects of resveratrol against PD, the precise mechanisms underlying its beneficial effects on dopaminergic neuron are poorly defined...
June 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28450223/gper-activation-is-effective-in-protecting-against-inflammation-induced-nigral-dopaminergic-loss-and-motor-function-impairment
#17
Julieta Mendes-Oliveira, Filipa Lopes Campos, Rita Alexandra Videira, Graça Baltazar
Increasing evidence suggest that excessive inflammatory responses from overactivated microglia play a critical role in Parkinson's disease (PD), contributing to, or exacerbating, nigral dopaminergic (DA) degeneration. Recent results from our group and others demonstrated that selective activation of G protein-coupled estrogen receptor (GPER) with the agonist G1 can protect DA neurons from 1-methyl-4-phenylpyridinium (MPP(+)) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxins. However, it is not known whether modulation of microglial responses is one of the mechanisms by which G1 exerts its DA neuroprotective effects...
April 24, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28446566/induction-of-adaptive-immunity-leads-to-nigrostriatal-disease-progression-in-mptp-mouse-model-of-parkinson-s-disease
#18
Goutam Chandra, Avik Roy, Suresh B Rangasamy, Kalipada Pahan
Although the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is the most widely used animal model for Parkinson's disease (PD), it is known that nigrostriatal pathologies do not persist in the acute MPTP mouse model. This study highlights the importance of adaptive immunity in driving persistent and progressive disease in acute MPTP-intoxicated mice. Although marked infiltration of T cells into the nigra was found on 1 d of MPTP insult, T cell infiltration decreased afterward, becoming normal on 30 d of insult...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28439627/nigral-injection-of-a-proteasomal-inhibitor-lactacystin-induces-widespread-glial-cell-activation-and-shows-various-phenotypes-of-parkinson-s-disease-in-young-and-adult-mouse
#19
Mari H Savolainen, Katrina Albert, Mikko Airavaara, Timo T Myöhänen
Proteinaceous inclusions, called Lewy bodies, are used as a pathological hallmark for Parkinson's disease (PD). Lewy bodies contain insoluble α-synuclein (aSyn) and many other ubiquitinated proteins, suggesting a role for protein degradation system failure in the PD pathogenesis. Indeed, proteasomal dysfunction has been linked to PD but commonly used in vivo toxin models, such as 6-OHDA or MPTP, do not have a significant effect on the proteasomal system or protein aggregation. Therefore, we wanted to study the characteristics of a proteasomal inhibitor, lactacystin, as a PD model on young and adult mice...
April 24, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28408878/reward-based-motor-adaptation-mediated-by-basal-ganglia
#20
Taegyo Kim, Khaldoun C Hamade, Dmitry Todorov, William H Barnett, Robert A Capps, Elizaveta M Latash, Sergey N Markin, Ilya A Rybak, Yaroslav I Molkov
It is widely accepted that the basal ganglia (BG) play a key role in action selection and reinforcement learning. However, despite considerable number of studies, the BG architecture and function are not completely understood. Action selection and reinforcement learning are facilitated by the activity of dopaminergic neurons, which encode reward prediction errors when reward outcomes are higher or lower than expected. The BG are thought to select proper motor responses by gating appropriate actions, and suppressing inappropriate ones...
2017: Frontiers in Computational Neuroscience
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