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https://www.readbyqxmd.com/read/28935882/clinical-and-radiological-diversity-in-genetically-confirmed-primary-familial-brain-calcification
#1
Shingo Koyama, Hidenori Sato, Ryota Kobayashi, Shinobu Kawakatsu, Masayuki Kurimura, Manabu Wada, Toru Kawanami, Takeo Kato
Primary familial brain calcification (PFBC) is a rare neuropsychiatric disorder with characteristic symmetrical brain calcifications. Patients with PFBC may have a variety of symptoms, although they also may be clinically asymptomatic. Parkinsonism is one of the most common movement disorders; however, the underlying mechanism remains unclear. This condition is typically transmitted in an autosomal dominant fashion. To date, mutations in SLC20A2, PDGFRB, PDGFB, and XPR1 have been reported to cause PFBC. The aim of the study was to identify the genetic cause of brain calcification in probands from three PFBC families and in 8 sporadic patients and to perform clinical and radiological assessments focusing on parkinsonism in mutation carriers...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934619/distinct-brain-metabolic-patterns-separately-associated-with-cognition-motor-function-and-aging-in-parkinson-s-disease-dementia
#2
Ji Hyun Ko, Audrey Katako, Maram Aljuaid, Andrew L Goertzen, Andrew Borys, Douglas E Hobson, Seok Min Kim, Chong Sik Lee
We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [(18)F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis...
August 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28933212/impact-of-traumatic-brain-injury-on-dopaminergic-transmission
#3
Yuan-Hao Chen, Eagle Yi-Kung Huang, Tung-Tai Kuo, Jonathan Miller, Yung-Hsiao Chiang, Barry J Hoffer
Brain trauma is often associated with severe morbidity and is a major public health concern. Even when injury is mild and no obvious anatomic disruption is seen, many individuals suffer disabling neuropsychological impairments such as memory loss, mood dysfunction, substance abuse, and adjustment disorder. These changes may be related to subtle disruption of neural circuits as well as functional changes at the neurotransmitter level. In particular, there is considerable evidence that dopamine (DA) physiology in the nigrostriatal and mesocorticolimbic pathways might be impaired after traumatic brain injury (TBI)...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28929131/spontaneous-eye-blink-rate-ebr-is-uncorrelated-with-dopamine-d2-receptor-availability-and-unmodulated-by-dopamine-agonism-in-healthy-adults
#4
Linh C Dang, Gregory R Samanez-Larkin, Jaime J Castrellon, Scott F Perkins, Ronald L Cowan, Paul A Newhouse, David H Zald
Spontaneous eye blink rate (EBR) has been proposed as a noninvasive, inexpensive marker of dopamine functioning. Support for a relation between EBR and dopamine function comes from observations that EBR is altered in populations with dopamine dysfunction and EBR changes under a dopaminergic manipulation. However, the evidence across the literature is inconsistent and incomplete. A direct correlation between EBR and dopamine function has so far been observed only in nonhuman animals. Given significant interest in using EBR as a proxy for dopamine function, this study aimed to verify a direct association in healthy, human adults...
September 2017: ENeuro
https://www.readbyqxmd.com/read/28927551/impaired-contextual-fear-conditioning-in-mam-rodent-model-of-schizophrenia
#5
Kathryn M Gill, Sarah A Miller, Anthony A Grace
The methylazoxymethanol acetate (MAM) rodent neurodevelopmental model of schizophrenia exhibits aberrant dopamine system activation attributed to hippocampal dysfunction. Context discrimination is a component of numerous behavioral and cognitive functions and relies on intact hippocampal processing. The present study explored context processing behaviors, along with dopamine system activation, during fear learning in the MAM model. Male offspring of dams treated with MAM (20mg/kg, i.p.) or saline on gestational day 17 were used for electrophysiological and behavioral experiments...
September 15, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28924188/dopamine-d1-receptor-subtype-mediates-acute-stress-induced-dendritic-growth-in-excitatory-neurons-of-the-medial-prefrontal-cortex-and-contributes-to-suppression-of-stress-susceptibility-in-mice
#6
R Shinohara, M Taniguchi, A T Ehrlich, K Yokogawa, Y Deguchi, Y Cherasse, M Lazarus, Y Urade, A Ogawa, S Kitaoka, A Sawa, S Narumiya, T Furuyashiki
Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC...
September 19, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28922168/evaluation-of-rna-blood-biomarkers-in-individuals-at-risk-of-parkinson-s-disease
#7
Jose A Santiago, Judith A Potashkin
BACKGROUND: Substantial progress has been made in the discovery of blood biomarkers for Parkinson's disease (PD), a progressive neurodegenerative disease that affects more than 4 million worldwide. Olfactory dysfunction and dopamine deficits usually precede motor symptoms years before the onset of PD. A readily accessible biomarker useful for identifying patients at risk of PD is expected to accelerate clinical trials. OBJECTIVE: To evaluate previously identified PD blood RNA biomarkers in a cohort of asymptomatic individuals at risk of PD...
September 11, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28912345/a-novel-bibenzyl-compound-20c-protected-mice-from-mptp-p-toxicity-by-regulating-alpha-synuclein-related-inflammatory-response
#8
Qiu-Shuang Zhang, Yang Heng, Ying Chen, Piao Luo, Lu Wen, Zhao Zhang, Yu-He Yuan, Nai-Hong Chen
The novel bibenzyl compound 20C plays a neuroprotective role in vitro, but its effects in vivo have not been elucidated. In this study, we estimated the efficacy of 20C in vivo using a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine/probenecid (MPTP/p) mouse model from behavior, dopamine and neuron, and then the possible mechanisms for these effects were further investigated. The experimental results showed that 20C improved behavioral deficits, attenuated dopamine depletion, reduced dopaminergic neuron loss, protected blood brain barrier structure, ameliorated α-synuclein dysfunction, suppressed glial activation, and regulated both NF-κB signaling and the NLRP3 inflammasome pathway...
September 14, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28912301/early-onset-drug-induced-parkinsonism-after-exposure-to-offenders-implies-nigrostriatal-dopaminergic-dysfunction
#9
Seok Jong Chung, Han Soo Yoo, Hyojeong Moon, Jungsu S Oh, Jae Seung Kim, Yong Hee Park, Jin Yong Hong, Byoung Seok Ye, Young H Sohn, Phil Hyu Lee
OBJECTIVES: The onset of parkinsonism in patients with drug-induced parkinsonism (DIP) exhibits extensive individual variability following exposure to offending drugs. We investigated whether the individual variations in the onset time of parkinsonism reflected the underlying subtle dopaminergic dysfunction in DIP. METHODS: We enrolled 71 patients with DIP who had visually normal striatal dopamine transporter (DAT) availability in (18)F-FP-CIT positron emission tomography scans...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28912019/a-nigro-vagal-pathway-controls-gastric-motility-and-is-affected-in-a-rat-model-of-parkinsonism
#10
Laura Anselmi, Luca Toti, Cecilia Bove, Jessica Hampton, R Alberto Travagli
BACKGROUND & AIMS: In most patients with Parkinson's disease, gastrointestinal (GI) dysfunctions, such as gastroparesis and constipation, are prodromal to the cardinal motor symptoms of the disease. Sporadic Parkinson's disease has been proposed to develop following ingestion of neurotoxicants that affect the brain-gut axis via the vagus nerve, and then travel to higher centers compromising the substantia nigra pars compacta (SNpc), and, later, the cerebral cortex. We aimed to identify the pathway that connects the brainstem vagal nuclei and the SNpc, and to determine whether this pathway is compromised in a rat model of Parkinsonism...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28910619/loss-of-hyperdirect-pathway-cortico-subthalamic-inputs-following-degeneration-of-midbrain-dopamine-neurons
#11
Hong-Yuan Chu, Eileen L McIver, Ryan F Kovaleski, Jeremy F Atherton, Mark D Bevan
The motor symptoms of Parkinson's disease (PD) are linked to abnormally correlated and coherent activity in the cortex and subthalamic nucleus (STN). However, in parkinsonian mice we found that cortico-STN transmission strength had diminished by 50%-75% through loss of axo-dendritic and axo-spinous synapses, was incapable of long-term potentiation, and less effectively patterned STN activity. Optogenetic, chemogenetic, genetic, and pharmacological interrogation suggested that downregulation of cortico-STN transmission in PD mice was triggered by increased striato-pallidal transmission, leading to disinhibition of the STN and increased activation of STN NMDA receptors...
September 13, 2017: Neuron
https://www.readbyqxmd.com/read/28895569/the-effects-of-the-monoamine-stabilizer-osu6162-on-binge-like-eating-and-cue-controlled-food-seeking-behavior-in-rats
#12
K Feltmann, C Giuliano, B J Everitt, P Steensland, J Alsiö
Binge eating disorder (BED) is characterized by recurring episodes of excessive consumption of palatable food and an increased sensitivity to food cues. Patients with BED display an addiction-like symptomatology and the dopamine system might be a potential treatment target. The clinically safe monoamine stabilizer (-)-OSU6162 (OSU6162) restores dopaminergic dysfunction in long-term alcohol drinking rats and shows promise as a novel treatment for alcohol use disorder. Here, the effects of OSU6162 on consummatory (binge-like eating) and appetitive (cue-controlled seeking) behavior motivated by chocolate-flavored sucrose pellets were evaluated in non-food-restricted male Lister Hooded rats...
September 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28894175/sexual-congruency-in-the-connectome-and-translatome-of-vta-dopamine-neurons
#13
Amanda S Chung, Samara M Miller, Yanjun Sun, Xiangmin Xu, Larry S Zweifel
The ventral tegmental area (VTA) dopamine system is important for reward, motivation, emotion, learning, and memory. Dysfunctions in the dopamine system are linked to multiple neurological and neuropsychiatric disorders, many of which present with sex differences. Little is known about the extent of heterogeneity in the basic organization of VTA dopamine neurons with regard to sex. Here, we characterized the cell-specific connectivity of VTA dopamine neurons, their mRNA translational profile, and basic electrophysiological characteristics in a common strain of mice...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28889266/occupational-metal-exposure-and-parkinsonism
#14
W Michael Caudle
Parkinsonism is comprised of a host of neurological disorders with an underlying clinical feature of movement disorder, which includes many shared features of bradykinesia, tremor, and rigidity. These clinical outcomes occur subsequent to pathological deficits focused on degeneration or dysfunction of the nigrostriatal dopamine system and accompanying pathological inclusions of alpha-synuclein and tau. The heterogeneity of parkinsonism is equally matched with the complex etiology of this syndrome. While a small percentage can be attributed to genetic alterations, the majority arise from an environmental exposure, generally composed of pesticides, industrial compounds, as well as metals...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28887183/electrical-stimulation-of-the-hippocampal-fimbria-facilitates-neuronal-nitric-oxide-synthase-activity-in-the-medial-shell-of-the-rat-nucleus-accumbens-modulation-by-dopamine-d1-and-d2-receptor-activation
#15
Kristina E Hoque, Shannon R Blume, Stephen Sammut, Anthony R West
The medial shell region of the nucleus accumbens (msNAc) is a key center for the regulation of goal-directed behavior and is likely to be dysfunctional in neuropsychiatric disorders such as addiction, depression and schizophrenia. Nitric oxide (NO)-producing interneurons in the msNAc are potently modulated by dopamine (DA) and may play an important role in synaptic integration in msNAc networks. In this study, neuronal NO synthase (nNOS) activity was measured in anesthetized rats using amperometric microsensors implanted into the msNAc or via histochemical techniques...
September 5, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28884460/potassium-channels-a-potential-therapeutic-target-for-parkinson-s-disease
#16
REVIEW
Xiaoyan Chen, Bao Xue, Jun Wang, Haixia Liu, Limin Shi, Junxia Xie
The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K(+)) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K(+) channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K(+) channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum...
September 7, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28883785/early-postnatal-but-not-late-adult-neurogenesis-is-impaired-in-the-pitx3-mutant-animal-model-of-parkinson-s-disease
#17
Moritz D Brandt, Diana Krüger-Gerlach, Andreas Hermann, Anne K Meyer, Kwang-Soo Kim, Alexander Storch
The generation of new neurons in the adult dentate gyrus has functional implications for hippocampal formation. Reduced hippocampal neurogenesis has been described in various animal models of hippocampal dysfunction such as dementia and depression, which are both common non-motor-symptoms of Parkinson's disease (PD). As dopamine plays an important role in regulating precursor cell proliferation, the loss of dopaminergic neurons in the substantia nigra (SN) in PD may be related to the reduced neurogenesis observed in the neurogenic regions of the adult brain: subventricular zone (SVZ) and dentate gyrus (DG)...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28882997/dopamine-oxidation-mediates-mitochondrial-and-lysosomal-dysfunction-in-parkinson-s-disease
#18
Lena F Burbulla, Pingping Song, Joseph R Mazzulli, Enrico Zampese, Yvette C Wong, Sohee Jeon, David P Santos, Judith Blanz, Carolin D Obermaier, Chelsee Strojny, Jeffrey N Savas, Evangelos Kiskinis, Xiaoxi Zhuang, Rejko Krüger, D James Surmeier, Dimitri Krainc
Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic neurons derived from patients with idiopathic and familial PD. We identified a time-dependent pathological cascade beginning with mitochondrial oxidant stress leading to oxidized dopamine accumulation and ultimately resulting in reduced glucocerebrosidase enzymatic activity, lysosomal dysfunction, and α-synuclein accumulation...
September 22, 2017: Science
https://www.readbyqxmd.com/read/28881616/repetitive-transcranial-magnetic-stimulation-for-treatment-of-lactacystin-induced-parkinsonian-rat-model
#19
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...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880525/mitoneet-cisd1-knockout-mice-show-signs-of-striatal-mitochondrial-dysfunction-and-a-parkinson-s-disease-phenotype
#20
Werner J Geldenhuys, Stanley A Benkovic, Li Lin, Heather M Yonutas, Samuel D Crish, Patrick G Sullivan, Altaf S Darvesh, Candice M Brown, Jason Richardson
Mitochondrial dysfunction is thought to play a significant role in neurodegeneration observed in Parkinson's disease (PD), yet the mechanisms underlying this pathology remain unclear. Here, we demonstrate that loss of mitoNEET (CISD1), an iron-sulfur containing protein which regulates mitochondrial bioenergetics, results in mitochondrial dysfunction and loss of striatal dopamine and tyrosine hydroxylase. Mitochondria isolated from mice lacking mitoNEET were dysfunctional as revealed by elevated reactive oxygen species (ROS) and reduced capacity to produce ATP...
September 7, 2017: ACS Chemical Neuroscience
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