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Substantia nigra

Arjun Sethi, Valerie Voon, Hugo D Critchley, Mara Cercignani, Neil A Harrison
Computational models of reinforcement learning have helped dissect discrete components of reward-related function and characterize neurocognitive deficits in psychiatric illnesses. Stimulus novelty biases decision-making, even when unrelated to choice outcome, acting as if possessing intrinsic reward value to guide decisions toward uncertain options. Heightened novelty seeking is characteristic of attention deficit hyperactivity disorder, yet how this influences reward-related decision-making is computationally encoded, or is altered by stimulant medication, is currently uncertain...
March 13, 2018: Brain: a Journal of Neurology
Ren-Hong Du, Hong-Bin Sun, Zhao-Li Hu, Ming Lu, Jian-Hua Ding, Gang Hu
Classical activation (M1 phenotype) and alternative activation (M2 phenotype) are the two polars of microglial activation states that can produce either neurotoxic or neuroprotective effects in the immune pathogenesis of Parkinson's disease (PD). Exploiting the beneficial properties of microglia cells by modulating their polarization states provides great potential for the treatment of PD. However, the mechanism that regulates microglia polarization remains elusive. Here we demonstrated that Kir6.1-containing ATP-sensitive potassium (Kir6...
March 14, 2018: Cell Death & Disease
Ahmed M Elkady, Dana Cobzas, Hongfu Sun, Gregg Blevins, Alan H Wilman
BACKGROUND: Combined R2* and quantitative susceptibility (QS) has been previously used in cross-sectional multiple sclerosis (MS) studies to distinguish deep gray matter (DGM) iron accumulation and demyelination. PURPOSE: We propose and apply discriminative analysis of regional evolution (DARE) to define specific changes in MS and healthy DGM. STUDY TYPE: Longitudinal (baseline and 2-year follow-up) retrospective study. SUBJECTS: Twenty-seven relapsing-remitting MS (RRMS), 17 progressive MS (PMS), and corresponding age-matched healthy subjects...
March 14, 2018: Journal of Magnetic Resonance Imaging: JMRI
Beth Grimmig, Lauren Daly, Meena Subbarayan, Ched Hudson, Robert Williamson, Kevin Nash, Paula C Bickford
Parkinson's disease (PD) is the second most common neurodegenerative disorder and prevalence increases with age. Normal physiological changes that occur during the aging process reflect the pathological characteristics of Parkinson's disease. It is also recognized that age related changes significantly interact with the pathological mechanisms that underlie the neurodegeneration in PD and perpetuate the disease process. Despite the fact that aging is considered to be a primary risk factor for developing PD, the use of aged animal models are still under-utilized in pre-clinical research, thus reducing the translatability of experimental findings...
February 13, 2018: Oncotarget
Rodrigo Novaes Ferreira, Aline Silva de Miranda, Natalia Pessoa Rocha, Ana Cristina Simoes E Silva, Antonio Lucio Teixeira, Elizabeth Ribeiro da Silva Camargos
BACKGROUND: Parkinson´s Disease (PD) is a chronic, progressive condition, being the second most common neurodegenerative disorder worldwide. The classical features include: bradykinesia, resting tremor, rigidity and festination. These neurological alterations are probably due to the death of dopaminergic neurons in the substantia nigra pars compacta and consequent reduction of dopamine input into the striatum. The decrease of dopamine levels may also be involved in the emergence of non-motor symptoms, including cognitive impairment, anxiety and depression symptoms...
March 12, 2018: Current Medicinal Chemistry
Claude Rouillard, Joanie Baillargeon, Brigitte Paquet, Michel St-Hilaire, Jérôme Maheux, Catherine Lévesque, Noémie Darlix, Simon Majeur, Daniel Lévesque
Parkinson's disease (PD) is an idiopathic progressive neurodegenerative disorder characterized by the loss of midbrain dopamine neurons. Levodopa (l-dopa) is the main pharmacological approach to relieve PD motor symptoms. However, chronic treatment with l-Dopa is inevitably associated with the generation of abnormal involuntary movements (l-Dopa-induced dyskinesia). We have previously shown that Nr4a1 (Nur77), a transcription factor of the nuclear receptor family, is closely associated with dopamine neurotransmission in the mature brain...
March 9, 2018: Experimental Neurology
Luqing Wei, Xiao Hu, Yonggui Yuan, Weiguo Liu, Hong Chen
Neuropathology suggests that Parkinson's disease (PD) with depression may involve a progressive degeneration of the nigrostriatal and mesocorticolimbic dopaminergic systems. Previous positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have shown that dopamine changes in individual brain regions constituting the nigrostriatal and mesocorticolimbic circuits are associated with depression in PD. However, few studies have been conducted on the circuit-level alterations in this disease...
March 9, 2018: Behavioural Brain Research
Susan J Melhorn, Mary K Askren, Wendy K Chung, Mario Kratz, Tyler A Bosch, Vidhi Tyagi, Mary F Webb, Mary Rosalynn B De Leon, Thomas J Grabowski, Rudolph L Leibel, Ellen A Schur
Background: Variants in the first intron of the fat mass and obesity-associated (FTO) gene increase obesity risk. People with "high-risk" FTO genotypes exhibit preference for high-fat foods, reduced satiety responsiveness, and greater food intake consistent with impaired satiety. Objective: We sought central nervous system mechanisms that might underlie impaired satiety perception in people with a higher risk of obesity based on their FTO genotype. Design: We performed a cross-sectional study in a sample that was enriched for obesity and included 20 higher-risk participants with the AA (risk) genotype at the rs9939609 locus of FTO and 94 lower-risk participants with either the AT or TT genotype...
February 1, 2018: American Journal of Clinical Nutrition
Koh Tadokoro, Yasuyuki Ohta, Kota Sato, Takahiro Maeki, Ryo Sasaki, Yoshiaki Takahashi, Jingwei Shang, Mami Takemoto, Nozomi Hishikawa, Toru Yamashita, Chang Kweng Lim, Shigeru Tajima, Koji Abe
Japanese encephalitis (JE) survivors often present with nigrostriatal aftereffects with parkinsonian features. A 67-year-old woman with JE showed right-dominant clinical parkinsonism and left-dominant substantia nigra lesions after magnetic resonance imaging (MRI). Dopamine transporter (DAT) imaging using123 I-labeled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123 I-FP-CIT) revealed a corresponding left-dominant decrease. The present case is the first to reveal a clear match of laterality between clinical parkinsonism, MRI-based substantia nigra lesions, and impaired DAT in presynaptic dopaminergic neurons in JE...
March 9, 2018: Internal Medicine
Hector R Mendez-Gomez, Jasbir Singh, Craig Meyers, Weijun Chen, Oleg S Gorbatyuk, Nicholas Muzyczka
Phospholipase D2 (PLD2), an enzyme involved in vesicle trafficking and membrane signaling, interacts with α-synuclein, a protein known to contribute in the development of Parkinson disease. We previously reported that PLD2 overexpression in rat substantia nigra pars compacta (SNc) causes a rapid neurodegeneration of dopamine neurons, and that α-synuclein suppresses PLD2-induced nigral degeneration (Gorbatyuk et al., 2010). Here, we report that PLD2 toxicity is due to its lipase activity. Overexpression of a catalytically inactive mutant (K758R) of PLD2 prevents the loss of dopaminergic neurons in the SNc and does not show signs of toxicity after 10 weeks of overexpression...
March 8, 2018: Neuroscience
F Vitale, A Capozzo, P Mazzone, E Scarnati
The interest in the pedunculopontine tegmental nucleus (PPTg), a structure located in the brainstem at the level of the pontomesencephalic junction, has greatly increased in recent years because it is involved in the regulation of physiological functions that fail in Parkinson's disease and because it is a promising target for deep brain stimulation in movement disorders. The PPTg is highly interconnected with the main basal ganglia nuclei and relays basal ganglia activity to thalamic and brainstem nuclei and to spinal effectors...
March 7, 2018: Neurobiology of Disease
Alex Yen-Yu Chen, Tim Tully
Parkinson's disease (PD) is a progressive motor neurodegenerative disorder, characterized by a selective loss of dopaminergic neurons in the substantia nigra. The complexity of disease etiology includes both genetic and environmental factors. No effective drug that can modify disease progression and protect dopamine neurons from degeneration is presently available. Human α-Synuclein A30P (A30P) is a mutant gene identified in early onset PD and showed to result selective dopamine neuron loss in transgenic A30P flies and mice...
March 7, 2018: Neurobiology of Disease
Li Gan, Delin Ma, Min Li, Fu-Chen Yang, Robert S Rogers, Joshua L Wheatley, Lauren G Koch, Steven L Britton, John P Thyfault, Paige C Geiger, John A Stanford
Aerobic capacity is a strong predictor of mortality. Low capacity runner (LCR) rats exhibit reduced mitochondrial function in peripheral organs. A high fat diet (HFD) can worsen metabolic phenotype in LCR rats. Little is known about metabolic changes in the brains of these rats, however. This study examined protein markers of mitochondrial function and metabolism as a function of aerobic running capacity and an acute HFD in four brain regions: the striatum, hippocampus, hypothalamus, and substantia nigra. After 3 days HFD or chow diets, we measured peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1-α), nuclear respiratory factors 1 (Nrf-1), mitochondrial transcription factor A (TFAM), and phosphorylated (activated) AMP-activated protein kinase (p-AMPK) protein levels in the four brain regions...
March 6, 2018: Neuroscience Letters
Jian Wang, Yuanfang Li, Zhen Huang, Wenbing Wan, Yong Zhang, Changpeng Wang, Xiaoqin Cheng, Fang Ye, Kai Liu, Guoqiang Fei, Mengsu Zeng, Lirong Jin
BACKGROUND: Neuromelanin of the brainstem, which is considered a marker of neurodegeneration in Parkinson's disease (PD), can be detected by T1-weighted neuromelanin-sensitive magnetic resonance imaging (NM-MRI). We aimed to investigate the NM-MRI features of de novo PD and to determine whether these features are associated with motor and non-motor symptoms in de novo PD patients. METHODS: Fifty-one patients with de novo PD (Hoehn and Yahr stage 1-2) and 28 healthy controls were recruited...
March 9, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Cybelle Façanha Barreto Medeiros-Linard, Belmira Lara da Silveira Andrade-da-Costa, Ricielle Lopes Augusto, Adriana Sereniki, Maria Teresa Sales Trevisan, Renata de Cássia Ribas Perreira, Francisco Thiago Correia de Souza, Glauber Ruda Feitoza Braz, Claudia Jacques Lagranha, Ivone Antônia de Souza, Almir Gonçalves Wanderley, Soraya S Smailli, Simone Sette Lopes Lafayette
Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100 mg/kg/day) 1 h before rotenone (3 mg/kg; s...
March 8, 2018: Neurotoxicity Research
Matthew L Neal, Alexa M Boyle, Kevin M Budge, Fayez F Safadi, Jason R Richardson
BACKGROUND: Neuroinflammation is one of the hallmarks of neurodegenerative diseases, such as Parkinson's disease (PD). Activation of glial cells, including microglia and astrocytes, is a characteristic of the inflammatory response. Glycoprotein non-metastatic melanoma protein B (GPNMB) is a transmembrane glycoprotein that releases a soluble signaling peptide when cleaved by ADAM10 or other extracellular proteases. GPNMB has demonstrated a neuroprotective role in animal models of ALS and ischemia...
March 8, 2018: Journal of Neuroinflammation
Stefania Ferraro, Anna Nigri, Maria Grazia Bruzzone, Luca Brivio, Alberto Proietti Cecchini, Mattia Verri, Luisa Chiapparini, Massimo Leone
Objective We tested the hypothesis of a defective functional connectivity between the posterior hypothalamus and diencephalic-mesencephalic regions in chronic cluster headache based on: a) clinical and neuro-endocrinological findings in cluster headache patients; b) neuroimaging findings during cluster headache attacks; c) neuroimaging findings in drug-refractory chronic cluster headache patients improved after successful deep brain stimulation. Methods Resting state functional magnetic resonance imaging, associated with a seed-based approach, was employed to investigate the functional connectivity of the posterior hypothalamus in chronic cluster headache patients (n = 17) compared to age and sex-matched healthy subjects (n = 16)...
January 1, 2018: Cephalalgia: An International Journal of Headache
Bahar Güntekin, Lütfü Hanoğlu, Dilan Güner, Nesrin H Yılmaz, Fadime Çadırcı, Nagihan Mantar, Tuba Aktürk, Derya D Emek-Savaş, Fahriye F Özer, Görsev Yener, Erol Başar
Parkinson's disease (PD) is a neurodegenerative disease that is characterized by loss of dopaminergic neurons in the substantia nigra. Mild Cognitive impairment (MCI) and dementia may come along with the disease. New indicators are necessary for detecting patients that are likely to develop dementia. Electroencephalogram (EEG) Delta responses are one of the essential electrophysiological indicators that could show the cognitive decline. Many research in literature showed an increase of delta responses with the increased cognitive load...
2018: Frontiers in Psychology
Yi Lu, Xiaoxia Zhang, Liangcai Zhao, Changwei Yang, Linlin Pan, Chen Li, Kun Liu, Guanghui Bai, Hongchang Gao, Zhihan Yan
Metabolic confusion has been linked to the pathogenesis of Parkinson's disease (PD), while the dynamic changes associated with the onset and progression of PD remain unclear. Herein, dynamic changes in metabolites were detected from the initiation to the development of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced Parkinsonism model to elucidate its potential metabolic mechanism. Ex vivo 1 H nuclear magnetic resonance (NMR) spectroscopy was used to measure metabolite changes in the striatum and substantia nigra (SN) of mice at 1, 7, and 21 days after injection of MPTP...
2018: Frontiers in Neuroscience
Mychal S Grames, Robert D Dayton, Kasey L Jackson, Adam D Richard, Xiaohong Lu, Ronald L Klein
Recombinant adeno-associated virus (AAV) vectors are a popular genetic approach in neuroscience because they confer such efficient transgene expression in the brain and spinal cord. A number of studies have used AAV to express pathological disease-related proteins in the dopaminergic neurons of the substantia nigra in situ ( e.g., α-synuclein to model aspects of Parkinson's disease). The neuropathology and neurodegeneration of Parkinson's disease occur in a circumscribed pattern in the brain, and one of the most important goals of any gene transfer study is accurate, pinpoint targeting...
March 7, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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