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Midbrain

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101. VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation (PubMed)

VMAT2-Mediated Neurotransmission from Midbrain Leptin Receptor Neurons in Feeding Regulation Leptin receptors (LepRs) expressed in the midbrain contribute to the action of leptin on feeding regulation. The midbrain neurons release a variety of neurotransmitters including dopamine (DA), glutamate and GABA. However, which neurotransmitter mediates midbrain leptin action on feeding remains unclear. Here, we showed that midbrain LepR neurons overlap with a subset of dopaminergic, GABAergic (...) and glutamatergic neurons. Specific removal of vesicular monoamine transporter 2 (VMAT2) in midbrain LepR neurons (KO mice) disrupted DA accumulation in vesicles, but failed to cause a significant change in the evoked release of either glutamate or GABA to downstream neurons. While KO mice showed no differences on chow, they presented a reduced high-fat diet (HFD) intake and resisted to HFD-induced obesity. Specific activation of midbrain LepR neurons promoted VMAT2-dependent feeding on chow and HFD. When

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2017 eNeuro

102. Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential (PubMed)

Expansion of human midbrain floor plate progenitors from induced pluripotent stem cells increases dopaminergic neuron differentiation potential Human induced pluripotent stem cells (hiPSCs) are invaluable to study developmental processes and disease mechanisms particularly in the brain. hiPSCs can be differentiated into mature and functional dopaminergic (DA) neurons. Having robust protocols for the generation of differentiated DA neurons from pluripotent cells is a prerequisite for the use (...) of hiPSCs to study disease mechanisms, for drug discovery, and eventually for cell replacement therapy. Here, we describe a protocol for generating and expanding large numbers of homogeneous midbrain floor plate progenitors (mFPPs) that retain efficient DA neurogenic potential over multiple passages and can be cryobanked. We demonstrate that expanded mFPPs have increased DA neuron potential and differentiate more efficiently and rapidly than progenitors generated by standard protocols. In addition

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2017 Scientific reports

103. Wernekink Commissure Syndrome Secondary to Bilateral Caudal Paramedian Midbrain Infarction Presenting with a Unique “Heart or V” Appearance Sign: Case Report and Review of the Literature (PubMed)

Wernekink Commissure Syndrome Secondary to Bilateral Caudal Paramedian Midbrain Infarction Presenting with a Unique “Heart or V” Appearance Sign: Case Report and Review of the Literature Wernekink commissure syndrome secondary to caudal paramedian midbrain infarction (CPMI) is a rare midbrain syndrome involving the decussation of the superior cerebellar peduncle in the caudal paramedian midbrain tegmentum. The central characteristics are constant bilateral cerebellar dysfunction, variable (...) eye movement disorders, and rare delayed palatal myoclonus. Following is a description of the case of a 60-year-old man who presented with dizziness, slurred speech, and difficulty walking. Neurological examination revealed bilateral cerebellar dysfunction and bilateral internuclear ophthalmoplegia (bilateral INO). Serial magnetic resonance imaging (MRI) revealed a lesion in the caudal paramedian midbrain with a "heart-shaped" sign on fluid-attenuation inversion recovery images and a "V-shaped

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2017 Frontiers in neurology

104. Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling (PubMed)

Midbrain-Hindbrain Boundary Morphogenesis: At the Intersection of Wnt and Fgf Signaling A constriction in the neural tube at the junction of the midbrain and hindbrain is a conserved feature of vertebrate embryos. The constriction is a defining feature of the midbrain-hindbrain boundary (MHB), a signaling center that patterns the adjacent midbrain and rostral hindbrain and forms at the junction of two gene expression domains in the early neural plate: an anterior otx2/wnt1 positive domain

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2017 Frontiers in neuroanatomy

105. Direct midbrain dopamine input to the suprachiasmatic nucleus accelerates circadian entrainment (PubMed)

Direct midbrain dopamine input to the suprachiasmatic nucleus accelerates circadian entrainment Dopamine (DA) neurotransmission controls behaviors important for survival, including voluntary movement, reward processing, and detection of salient events, such as food or mate availability. Dopaminergic tone also influences circadian physiology and behavior. Although the evolutionary significance of this input is appreciated, its precise neurophysiological architecture remains unknown. Here, we

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2017 Current biology : CB

106. Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line (PubMed)

Expression patterns of key Sonic Hedgehog signaling pathway components in the developing and adult mouse midbrain and in the MN9D cell line The temporal dynamic expression of Sonic Hedgehog (SHH) and signaling during early midbrain dopaminergic (mDA) neuron development is one of the key players in establishing mDA progenitor diversity. However, whether SHH signaling is also required during later developmental stages and in mature mDA neurons is less understood. We study the expression of SHH (...) receptors Ptch1 and Gas1 (growth arrest-specific 1) and of the transcription factors Gli1, Gli2 and Gli3 in mouse midbrain during embryonic development [embryonic day (E) 12.5 onwards)], in newborn and adult mice using in situ hybridization and immunohistochemistry. Moreover, we examine the expression and regulation of dopaminergic neuronal progenitor markers, midbrain dopaminergic neuronal markers and markers of the SHH signaling pathway in undifferentiated and butyric acid-treated (differentiated

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2017 Cell and tissue research

107. Treatment Associated Changes of Functional Connectivity of Midbrain/Brainstem Nuclei in Major Depressive Disorder (PubMed)

Treatment Associated Changes of Functional Connectivity of Midbrain/Brainstem Nuclei in Major Depressive Disorder Previous functional magnetic resonance imaging (fMRI) studies demonstrated an abnormally coordinated network functioning in Major Depression Disorder (MDD) during rest. The main monoamine-producing nuclei within midbrain/brainstem are functionally integrated within these specific networks. Therefore, we aimed to investigate the resting-state functional connectivity (RSFC (...) activation in MDD. The observed differences in the FC of the midbrain/brainstem nuclei between two classes of antidepressants suggest differential neural effects of SSRIs and SNRIs.

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2017 Scientific reports

108. Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation (PubMed)

Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation Neural connectivity requires neuronal differentiation, axon growth, and precise target innervation. Midbrain dopaminergic neurons project via the nigrostriatal pathway to the striatum to regulate voluntary movement. While the specification and differentiation of these neurons have been extensively studied, the molecular mechanisms that regulate midbrain dopaminergic axon growth and target innervation (...) are less clear. Here we show that the transcription factor Zeb2 cell-autonomously represses Smad signalling to limit midbrain dopaminergic axon growth and target innervation. Zeb2 levels are downregulated in the embryonic rodent midbrain during the period of dopaminergic axon growth, when BMP pathway components are upregulated. Experimental knockdown of Zeb2 leads to an increase in BMP-Smad-dependent axon growth. Consequently there is dopaminergic hyperinnervation of the striatum, without an increase

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2017 Scientific reports

109. Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform (PubMed)

Efficient generation of hPSC-derived midbrain dopaminergic neurons in a fully defined, scalable, 3D biomaterial platform Pluripotent stem cells (PSCs) have major potential as an unlimited source of functional cells for many biomedical applications; however, the development of cell manufacturing systems to enable this promise faces many challenges. For example, there have been major recent advances in the generation of midbrain dopaminergic (mDA) neurons from stem cells for Parkinson's Disease

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2017 Scientific reports

110. Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain (PubMed)

Putative presynaptic dopamine dysregulation in schizophrenia is supported by molecular evidence from post-mortem human midbrain The dopamine hypothesis of schizophrenia posits that increased subcortical dopamine underpins psychosis. In vivo imaging studies indicate an increased presynaptic dopamine synthesis capacity in striatal terminals and cell bodies in the midbrain in schizophrenia; however, measures of the dopamine-synthesising enzyme, tyrosine hydroxylase (TH), have not identified (...) consistent changes. We hypothesise that dopamine dysregulation in schizophrenia could result from changes in expression of dopamine synthesis enzymes, receptors, transporters or catabolic enzymes. Gene expression of 12 dopamine-related molecules was examined in post-mortem midbrain (28 antipsychotic-treated schizophrenia cases/29 controls) using quantitative PCR. TH and the synaptic dopamine transporter (DAT) proteins were examined in post-mortem midbrain (26 antipsychotic-treated schizophrenia cases per

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2017 Translational psychiatry

111. Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly (PubMed)

Reward Dependent Invigoration Relates to Theta Oscillations and Is Predicted by Dopaminergic Midbrain Integrity in Healthy Elderly Motivation can have invigorating effects on behavior via dopaminergic neuromodulation. While this relationship has mainly been established in theoretical models and studies in younger subjects, the impact of structural declines of the dopaminergic system during healthy aging remains unclear. To investigate this issue, we used electroencephalography (EEG) in healthy

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2017 Frontiers in aging neuroscience

112. Hierarchical prediction errors in midbrain and septum during social learning (PubMed)

Hierarchical prediction errors in midbrain and septum during social learning Social learning is fundamental to human interactions, yet its computational and physiological mechanisms are not well understood. One prominent open question concerns the role of neuromodulatory transmitters. We combined fMRI, computational modelling and genetics to address this question in two separate samples (N = 35, N = 47). Participants played a game requiring inference on an adviser's intentions whose motivation (...) to help or mislead changed over time. Our analyses suggest that hierarchically structured belief updates about current advice validity and the adviser's trustworthiness, respectively, depend on different neuromodulatory systems. Low-level prediction errors (PEs) about advice accuracy not only activated regions known to support 'theory of mind', but also the dopaminergic midbrain. Furthermore, PE responses in ventral striatum were influenced by the Met/Val polymorphism of the Catechol-O

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2017 Social cognitive and affective neuroscience

113. Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure (PubMed)

Tualang Honey Protects the Rat Midbrain and Lung against Repeated Paraquat Exposure Paraquat (PQ) is a dopaminergic neurotoxin and a well-known pneumotoxicant that exerts its toxic effect via oxidative stress-mediated cellular injuries. This study investigated the protective effects of Tualang honey against PQ-induced toxicity in the midbrain and lungs of rats. The rats were orally treated with distilled water (2 mL/kg/day), Tualang honey (1.0 g/kg/day), or ubiquinol (0.2 g/kg/day) throughout (...) the experimental period. Two weeks after the respective treatments, the rats were injected intraperitoneally with saline (1 mL/kg/week) or PQ (10 mg/kg/week) once per week for four consecutive weeks. After four weekly exposures to PQ, the glutathione peroxidase activity and the number of tyrosine-hydroxylase immunopositive neurons in the midbrain were significantly decreased in animals from group PQ (p < 0.05). The lungs of animals from group PQ showed significantly decreased activity of superoxide dismutase

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2017 Oxidative medicine and cellular longevity

114. Medial Rectus Nuclear Palsy as a Sole Feature of Midbrain Infarction Secondary to Stenosis of Posterior Cerebral Artery (PubMed)

Medial Rectus Nuclear Palsy as a Sole Feature of Midbrain Infarction Secondary to Stenosis of Posterior Cerebral Artery 28051035 2017 03 13 2018 11 13 2542-5641 130 1 2017 01 05 Chinese medical journal Chin. Med. J. Medial Rectus Nuclear Palsy as a Sole Feature of Midbrain Infarction Secondary to Stenosis of Posterior Cerebral Artery. 113-114 10.4103/0366-6999.196576 Zhang Zhi-Yong ZY Department of Neurology, China-Japan Friendship Hospital, Beijing 100029, China. Liu Zun-Jing ZJ Department

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2017 Chinese medical journal

115. Habenula-Induced Inhibition of Midbrain Dopamine Neurons Is Diminished by Lesions of the Rostromedial Tegmental Nucleus (PubMed)

Habenula-Induced Inhibition of Midbrain Dopamine Neurons Is Diminished by Lesions of the Rostromedial Tegmental Nucleus Neurons in the lateral habenula (LHb) are transiently activated by aversive events and have been implicated in associative learning. Functional changes associated with tonic and phasic activation of the LHb are often attributed to a corresponding inhibition of midbrain dopamine (DA) neurons. Activation of GABAergic neurons in the rostromedial tegmental nucleus (RMTg), a region (...) that receives dense projections from the LHb and projects strongly to midbrain monoaminergic nuclei, is believed to underlie the transient inhibition of DA neurons attributed to activation of the LHb. To test this premise, the effects of axon-sparing lesions of the RMTg were assessed on LHb-induced inhibition of midbrain DA cell firing in anesthetized rats. Quinolinic acid lesions decreased the number of NeuN-positive neurons in the RMTg significantly while largely sparing cells in neighboring regions

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2017 The Journal of Neuroscience

116. Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain (PubMed)

Effects of diet and insulin on dopamine transporter activity and expression in rat caudate-putamen, nucleus accumbens, and midbrain Food restriction (FR) and obesogenic (OB) diets are known to alter brain dopamine transmission and exert opposite modulatory effects on behavioral responsiveness to psychostimulant drugs of abuse. Mechanisms underlying these diet effects are not fully understood. In this study, we examined diet effects on expression and function of the dopamine transporter (DAT (...) ) in caudate-putamen (CPu), nucleus accumbens (NAc), and midbrain regions. Dopamine (DA) uptake by CPu, NAc or midbrain synapto(neuro)somes was measured in vitro with rotating disk electrode voltammetry or with [3 H]DA uptake and was found to correlate with DAT surface expression, assessed by maximal [3 H](-)-2-β-carbomethoxy-3-β-(4-fluorophenyl)tropane binding and surface biotinylation assays. FR and OB diets were both found to decrease DAT activity in CPu with a corresponding decrease in surface

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2017 Journal of neurochemistry

117. Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways (PubMed)

Homophilic binding of the neural cell adhesion molecule CHL1 regulates development of ventral midbrain dopaminergic pathways Abnormal development of ventral midbrain (VM) dopaminergic (DA) pathways, essential for motor and cognitive function, may underpin a number of neurological disorders and thereby highlight the importance of understanding the birth and connectivity of the associated neurons. While a number of regulators of VM DA neurogenesis are known, processes involved in later

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2017 Scientific reports

118. LOSS OF HYPERDIRECT PATHWAY CORTICO-SUBTHALAMIC INPUTS FOLLOWING DEGENERATION OF MIDBRAIN DOPAMINE NEURONS (PubMed)

LOSS OF HYPERDIRECT PATHWAY CORTICO-SUBTHALAMIC INPUTS FOLLOWING DEGENERATION OF MIDBRAIN DOPAMINE NEURONS 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

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2017 Neuron

119. OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS (PubMed)

OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH ALTERED MIDBRAIN CHEMICAL CONCENTRATIONS Obstructive sleep apnea (OSA) is accompanied by altered structure and function in cortical, limbic, brainstem, and cerebellar regions. The midbrain is relatively unexamined, but contains many integrative nuclei which mediate physiological functions that are disrupted in OSA. We therefore assessed the chemistry of the midbrain in OSA in this exploratory study. We used a recently developed accelerated 2D magnetic (...) resonance spectroscopy (2D-MRS) technique, compressed sensing-based 4D echo-planar J-resolved spectroscopic imaging (4D-EP-JRESI), to measure metabolites in the midbrain of 14 OSA (mean age±SD:54.6±10.6years; AHI:35.0±19.4; SAO2 min:83±7%) and 26 healthy control (50.7±8.5years) subjects. High-resolution T1-weighted scans allowed voxel localization. MRS data were processed with custom MATLAB-based software, and metabolite ratios calculated with respect to the creatine peak using a prior knowledge fitting

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2017 Neuroscience

120. Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease (PubMed)

Vitamin C-Induced Epigenetic Modifications in Donor NSCs Establish Midbrain Marker Expressions Critical for Cell-Based Therapy in Parkinson's Disease Cultured neural stem/precursor cells (NSCs) are regarded as a potential systematic cell source to treat Parkinson's disease (PD). However, the therapeutic potential of these cultured NSCs is lost during culturing. Here, we show that treatment of vitamin C (VC) enhances generation of authentic midbrain-type dopamine (mDA) neurons with improved (...) survival and functions from ventral midbrain (VM)-derived NSCs. VC acted by upregulating a series of mDA neuron-specific developmental and phenotype genes via removal of DNA methylation and repressive histone code (H3K9m3, H3K27m3) at associated gene promoter regions. Notably, the epigenetic changes induced by transient VC treatment were sustained long after VC withdrawal. Accordingly, transplantation of VC-treated NSCs resulted in improved behavioral restoration, along with enriched DA neuron

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2017 Stem cell reports

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