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Midbrain dopaminergic neuron

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https://www.readbyqxmd.com/read/29782623/astrocytic-hypertrophy-in-the-rat-ventral-tegmental-area-following-chronic-morphine-differs-with-age
#1
Emily C Goins, Dusica Bajic
The ventral tegmental area (VTA) is the origin of the mesolimbic dopaminergic system known to play an integral role in mediating reward and development of drug addiction. Although the differences in neuronal plasticity of VTA at various ages remain to be understood, age is known to influence the effects of chronic opioids. In addition, adaptations associated with exposure to opioids within glial populations located in the VTA are poorly understood. The objective of the study was to determine if there are changes in astrocytic immunofluorescent labeling in the VTA following chronic morphine administration in a rat model at different ages: newborn at postnatal day (PD)7 and adult (estimated PD57)...
2018: Journal of neurology and neurorehabilitation research
https://www.readbyqxmd.com/read/29778899/dopamine-loss-alters-the-hippocampus-nucleus-accumbens-synaptic-transmission-in-the-tg2576-mouse-model-of-alzheimer-s-disease
#2
Alberto Cordella, Paraskevi Krashia, Annalisa Nobili, Annabella Pignataro, Livia La Barbera, Maria Teresa Viscomi, Alessandro Valzania, Flavio Keller, Martine Ammassari-Teule, Nicola Biagio Mercuri, Nicola Berretta, Marcello D'Amelio
The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD...
May 17, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29778792/valproic-acid-attenuates-manganese-induced-reduction-in-expression-of-glt-1-and-glast-with-concomitant-changes-in-murine-dopaminergic-neurotoxicity
#3
James Johnson, Edward Pajarillo, Pratap Karki, Judong Kim, Deok-Soo Son, Michael Aschner, Eunsook Lee
Exposure to elevated levels of manganese (Mn) causes manganism, a neurological disorder with similar characteristics to those of Parkinson's disease (PD). Valproic acid (VPA), an antiepileptic, is known to inhibit histone deacetylases and exert neuroprotective effects in many experimental models of neurological disorders. In the present study, we investigated if VPA attenuated Mn-induced dopaminergic neurotoxicity and the possible mechanisms involved in VPA's neuroprotection, focusing on modulation of astrocytic glutamate transporters (glutamate aspartate transporter, GLAST and glutamate transporter 1, GLT-1) and histone acetylation in H4 astrocyte culture and mouse models...
May 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29775679/identification-and-validation-of-midbrain-kcnq4-regulation-of-heavy-alcohol-consumption-in-rodents
#4
Natalie S McGuier, Jennifer A Rinker, Reginald Cannady, Diana B Fulmer, Sara R Jones, Michaela Hoffman, Patrick J Mulholland
Currently available pharmacotherapies for treating alcohol use disorder (AUD) suffer from deleterious side effects and are not efficacious in diverse populations. Clinical and preclinical studies provide evidence that the Kcnq family of genes that encode KV 7 channels influence alcohol intake and dependence. KV 7 channels are a class of slowly activating voltage-dependent K+ channels that regulate neuronal excitability. Studies indicate that the KV 7 channel positive modulator retigabine can decrease dopaminergic neuron firing, alter dopamine (DA) release, and reduce alcohol intake in heavy drinking rodents...
May 15, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29773830/circadian-and-homeostatic-modulation-of-multi-unit-activity-in-midbrain-dopaminergic-structures
#5
Karim Fifel, Johanna H Meijer, Tom Deboer
Although the link between sleep disturbances and dopamine (DA)-related neurological and neuropsychiatric disorders is well established, the impact of sleep alterations on neuronal activity of midbrain DA-ergic structures is currently unknown. Here, using wildtype C57Bl mice, we investigated the circadian- and sleep-related modulation of electrical neuronal activity in midbrain ventral-tegmental-area (VTA) and substantia nigra (SN). We found no significant circadian modulation of activity in SN while VTA displayed a low amplitude but significant circadian modulation with increased firing rates during the active phase...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29769744/nadph-ameliorates-mptp-induced-dopaminergic-neurodegeneration-through-inhibiting-p38mapk-activation
#6
Jing-Si Zhou, Zhou Zhu, Feng Wu, Ying Zhou, Rui Sheng, Jun-Chao Wu, Zheng-Hong Qin
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+ ...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29760073/regulation-of-myeloid-cell-phagocytosis-by-lrrk2-via-wave2-complex-stabilization-is-altered-in-parkinson-s-disease
#7
Kwang Soo Kim, Paul C Marcogliese, Jungwoo Yang, Steve M Callaghan, Virginia Resende, Elizabeth Abdel-Messih, Connie Marras, Naomi P Visanji, Jana Huang, Michael G Schlossmacher, Laura Trinkle-Mulcahy, Ruth S Slack, Anthony E Lang, David S Park
Leucine-rich repeat kinase 2 ( LRRK2 ) has been implicated in both familial and sporadic Parkinson's disease (PD), yet its pathogenic role remains unclear. A previous screen in Drosophila identified Scar/WAVE (Wiskott-Aldrich syndrome protein-family verproline) proteins as potential genetic interactors of LRRK2 Here, we provide evidence that LRRK2 modulates the phagocytic response of myeloid cells via specific modulation of the actin-cytoskeletal regulator, WAVE2. We demonstrate that macrophages and microglia from LRRK2-G2019S PD patients and mice display a WAVE2-mediated increase in phagocytic response, respectively...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29751760/regional-microglia-are-transcriptionally-distinct-but-similarly-exacerbate-neurodegeneration-in-a-culture-model-of-parkinson-s-disease
#8
Eric Wildon Kostuk, Jingli Cai, Lorraine Iacovitti
BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP+ )...
May 11, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29741516/the-influence-of-anesthetics-on-substantia-nigra-tyrosine-hydroxylase-expression-and-tau-phosphorylation-in-the-hypoxic-ischemic-near-term-lamb
#9
Melinda Barkhuizen, Fleur J P van Dijck, Reint K Jellema, Ruth Gussenhoven, Imke Engelbertink, Ralph van Mechelen, Jack P M Cleutjens, Matthias Seehase, Harry W M Steinbusch, Luc J Zimmermann, A W Danilo Gavilanes, Boris W Kramer
BackgroundGeneral anesthetics could protect key neurotransmitter systems, such as the dopaminergic system, from hypoxic-ischemic encephalopathy (HIE) by limiting excessive glutamatergic neurotransmission. However, anesthetics may adversely affect inflammation and tau phosphorylation.MethodsA near-term sheep model of HIE by umbilical cord occlusion (UCO) under anesthesia was used. The effect of propofol and isoflurane on the dopaminergic neurotransmitter phenotype in the substantia nigra (SN) was studied using tyrosine hydroxylase immunohistochemistry...
May 9, 2018: Pediatric Research
https://www.readbyqxmd.com/read/29731707/the-neuroprotection-of-low-dose-morphine-in-cellular-and-animal-models-of-parkinson-s-disease-through-ameliorating-endoplasmic-reticulum-er-stress-and-activating-autophagy
#10
Bing Wang, Cun-Jin Su, Teng-Teng Liu, Yan Zhou, Yu Feng, Ya Huang, Xu Liu, Zhi-Hong Wang, Li-Hua Chen, Wei-Feng Luo, Tong Liu
Parkinson's disease (PD) is a common neurodegenerative disease characterized the progressive loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Brain endogenous morphine biosynthesis was reported to be impaired in PD patients and exogenous morphine attenuated 6-hydroxydopamine (6-OHDA)-induced cell death in vitro . However, the mechanisms underlying neuroprotection of morphine in PD are still unclear. In the present study, we investigated the neuroprotective effects of low-dose morphine in cellular and animal models of PD and the possible underlying mechanisms...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29729086/the-novel-atypical-antipsychotic-cariprazine-demonstrates-dopamine-d-2-receptor-dependent-partial-agonist-actions-on-rat-mesencephalic-dopamine-neuronal-activity
#11
Sarah Delcourte, Charles R Ashby, Renaud Rovera, Béla Kiss, Nika Adham, Bence Farkas, Nasser Haddjeri
AIM: Cariprazine, a dopamine D3 -preferring D3 /D2 receptor partial agonist, is FDA approved for the treatment of schizophrenia and acute manic or mixed episodes of bipolar disorder. This study used in vivo electrophysiological techniques in anesthetized rats to determine cariprazine's effect on dopaminergic cell activity in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). METHODS: Extracellular recordings of individual dopaminergic neurons were performed after oral or intravenous administration of cariprazine, the D3 receptor antagonist SB 277011A, the D2 receptor antagonist L741,626, and/or the D3 receptor agonist PD 128,907...
May 4, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29727632/the-oscillatory-boundary-conditions-of-different-frequency-bands-in-parkinson-s-disease
#12
Bing Hu, Qianqian Shi, Yu Guo, Xiyezi Diao, Heng Guo, Jinsong Zhang, Liang Yu, Hao Dai, Luonan Chen
Parkinson's disease (PD) is a neurodegenerative disease that is common in the elderly population. The most important pathological change in PD is the degeneration and death of dopaminergic neurons in the substantia nigra of the midbrain, which results in a decrease in the dopamine (DA) content of the striatum. The exact cause of this pathological change is still unknown. Numerous studies have shown that the evolution of PD is associated with abnormal oscillatory activities in the basal ganglia, with different oscillation frequency ranges, such as the typical beta band (13-30 Hz), the alpha band (8-12 Hz), the theta band (4-7 Hz) and the delta band (1-3 Hz)...
May 1, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29726929/impaired-mitochondrial-dynamics-underlie-axonal-defects-in-hereditary-spastic-paraplegias
#13
Kyle Denton, Yongchao Mou, Chong-Chong Xu, Dhruvi Shah, Jaerak Chang, Craig Blackstone, Xue-Jun Li
Mechanisms by which long corticospinal axons degenerate in hereditary spastic paraplegia (HSP) are largely unknown. Here, we have generated induced pluripotent stem cells (iPSCs) from patients with two autosomal recessive forms of HSP, SPG15 and SPG48, which are caused by mutations in the ZFYVE26 and AP5Z1 genes encoding proteins in the same complex, the spastizin and AP5Z1 proteins, respectively. In patient iPSC-derived telencephalic glutamatergic and midbrain dopaminergic neurons, neurite number, length and branching are significantly reduced, recapitulating disease-specific phenotypes...
May 2, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29714688/combinatorial-programming-of-human-neuronal-progenitors-using-magnetically-guided-stoichiometric-mrna-delivery
#14
Sayyed M Azimi, Steven D Sheridan, Mostafa Ghannad-Rezaie, Peter M Eimon, Mehmet Fatih Yanik
Identification of optimal transcription-factor expression patterns to direct cellular differentiation along a desired pathway presents significant challenges. We demonstrate massively combinatorial screening of temporally-varying mRNA transcription factors to direct differentiation of neural progenitor cells using a dynamically-reconfigurable magnetically-guided spotting technology for localizing mRNA, enabling experiments on millimetre size spots. In addition, we present a time-interleaved delivery method that dramatically reduces fluctuations in the delivered transcription-factor copy-numbers per cell...
May 1, 2018: ELife
https://www.readbyqxmd.com/read/29709269/polysulfide-protects-midbrain-dopaminergic-neurons-from-mpp-induced-degeneration-via-enhancement-of-glutathione-biosynthesis
#15
Shuhei Takahashi, Akinori Hisatsune, Yuki Kurauchi, Takahiro Seki, Hiroshi Katsuki
Polysulfides are endogenous sulfur-containing molecular species that may regulate various cellular functions. Here we examined the effect of polysulfides exogenously applied to rat midbrain slice cultures, to address their potential neuroprotective actions. Na2 S3 at concentrations of 10 μM or higher prevented 1-methyl-4-phenylpyridinium (MPP+ )-induced loss of dopaminergic neurons. Na2 S4 at 10 μM also protected dopaminergic neurons from MPP+ cytotoxicity, whereas Na2 S and Na2 S2 at the same concentration had no significant effect...
April 20, 2018: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29705795/leucine-rich-repeat-kinase-2-in-parkinson-s-disease-updated-from-pathogenesis-to-potential-therapeutic-target
#16
Jinhua Chen, Ying Chen, Jiali Pu
BACKGROUND: Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the midbrain. The pathogenesis of PD is not fully understood but is likely caused by a combination of genetic and environmental factors. Several genes are associated with the onset and progression of familial PD. There is increasing evidence that leucine-rich repeat kinase 2 (LRRK2) plays a significant role in PD pathophysiology. SUMMARY: Many studies have been conducted to elucidate the functions of LRRK2 and identify effective LRRK2 inhibitors for PD treatment...
April 27, 2018: European Neurology
https://www.readbyqxmd.com/read/29689292/tgf-%C3%AE-signalling-regulates-development-of-midbrain-dopaminergic-and-hindbrain-serotonergic-neuron-subgroups
#17
Enaam Chleilat, Lena Skatulla, Belal Rahhal, Manal T Hussein, Melanie Feuerstein, Kerstin Krieglstein, Eleni Roussa
Molecular and functional diversity within midbrain dopaminergic (mDA) and hindbrain serotonergic (5-HT) neurons has emerged as a relevant feature that could underlie selective vulnerability of neurons in clinical disorders. We have investigated the role of Transforming Growth Factor beta (TGF-β) during development of mDA and 5-HT subgroups. We have generated TβRIIflox/flox ::En1cre/+ mice where type II TGF-β receptor is conditionally deleted from engrailed 1- expressing cells and have investigated the hindbrain serotonergic system of these mice together with Tgf-β2-/- mice...
April 21, 2018: Neuroscience
https://www.readbyqxmd.com/read/29686225/identity-prediction-errors-in-the-human-midbrain-update-reward-identity-expectations-in-the-orbitofrontal-cortex
#18
James D Howard, Thorsten Kahnt
There is general consensus that dopaminergic midbrain neurons signal reward prediction errors, computed as the difference between expected and received reward value. However, recent work in rodents shows that these neurons also respond to errors related to inferred value and sensory features, indicating an expanded role for dopamine beyond learning cached values. Here we utilize a transreinforcer reversal learning task and functional magnetic resonance imaging (fMRI) to test whether prediction error signals in the human midbrain are evoked when the expected identity of an appetitive food odor reward is violated, while leaving value matched...
April 23, 2018: Nature Communications
https://www.readbyqxmd.com/read/29681884/glutathione-s-transferase-alpha-4-prevents-dopamine-neurodegeneration-in-a-rat-alpha-synuclein-model-of-parkinson-s-disease
#19
Michael Jewett, Elna Dickson, Kajsa Brolin, Matilde Negrini, Itzia Jimenez-Ferrer, Maria Swanberg
Parkinson's disease (PD) is a common, progressive neurodegenerative disease, which typically presents itself with a range of motor symptoms, like resting tremor, bradykinesia, and rigidity, but also non-motor symptoms such as fatigue, constipation, and sleep disturbance. Neuropathologically, PD is characterized by loss of dopaminergic cells in the substantia nigra pars compacta (SNpc) and Lewy bodies, neuronal inclusions containing α-synuclein (α-syn). Mutations and copy number variations of SNCA , the gene encoding α-syn, are linked to familial PD and common SNCA gene variants are associated to idiopathic PD...
2018: Frontiers in Neurology
https://www.readbyqxmd.com/read/29681476/phasic-dopamine-signals-in-the-nucleus-accumbens-that-cause-active-avoidance-require-endocannabinoid-mobilization-in-the-midbrain
#20
Jennifer M Wenzel, Erik B Oleson, Willard N Gove, Anthony B Cole, Utsav Gyawali, Hannah M Dantrassy, Rebecca J Bluett, Dilyan I Dryanovski, Garret D Stuber, Karl Deisseroth, Brian N Mathur, Sachin Patel, Carl R Lupica, Joseph F Cheer
Phasic dopamine (DA) release accompanies approach toward appetitive cues. However, a role for DA in the active avoidance of negative events remains undetermined. Warning signals informing footshock avoidance are associated with accumbal DA release, whereas depression of DA is observed with unavoidable footshock. Here, we reveal a causal role of phasic DA in active avoidance learning; specifically, optogenetic activation of DA neurons facilitates avoidance, whereas optical inhibition of these cells attenuates it...
April 16, 2018: Current Biology: CB
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