scholarly journals Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice

2018 ◽  
Vol 115 (49) ◽  
pp. E11532-E11541 ◽  
Author(s):  
Hui Shen ◽  
Rosa Anna M. Marino ◽  
Ross A. McDevitt ◽  
Guo-Hua Bi ◽  
Kai Chen ◽  
...  
Keyword(s):  
Glutamate Release ◽  
Glutamate Transporter ◽  
Dopamine Neurons ◽  
Therapeutic Interventions ◽  
Vesicular Glutamate Transporter ◽  
Increased Risk ◽  
Locomotor Impairment ◽  
Functional Consequences ◽  
Midbrain Dopamine ◽  
And Function

A subset of midbrain dopamine (DA) neurons express vesicular glutamate transporter 2 (VgluT2), which facilitates synaptic vesicle loading of glutamate. Recent studies indicate that such expression can modulate DA-dependent reward behaviors, but little is known about functional consequences of DA neuron VgluT2 expression in neurodegenerative diseases like Parkinson’s disease (PD). Here, we report that selective deletion of VgluT2 in DA neurons in conditional VgluT2-KO (VgluT2-cKO) mice abolished glutamate release from DA neurons, reduced their expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB), and exacerbated the pathological effects of exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, viral rescue of VgluT2 expression in DA neurons of VglutT2-cKO mice restored BDNF/TrkB expression and attenuated MPTP-induced DA neuron loss and locomotor impairment. Together, these findings indicate that VgluT2 expression in DA neurons is neuroprotective. Genetic or environmental factors causing reduced expression or function of VgluT2 in DA neurons may place some individuals at increased risk for DA neuron degeneration. Therefore, maintaining physiological expression and function of VgluT2 in DA neurons may represent a valid molecular target for the development of preventive therapeutic interventions for PD.

scholarly journals Electrical and Ca2+ signaling in dendritic spines of substantia nigra dopaminergic neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Travis A Hage ◽  
Yujie Sun ◽  
Zayd M Khaliq
Keyword(s):  
Dendritic Spines ◽  
Dopaminergic Neurons ◽  
Fluorescence Recovery After Photobleaching ◽  
Dopamine Neurons ◽  
Fixed Tissue ◽  
Spine Length ◽  
Relative Contribution ◽  
Midbrain Dopamine ◽  
Shaft Synapses ◽  
And Function

Little is known about the density and function of dendritic spines on midbrain dopamine neurons, or the relative contribution of spine and shaft synapses to excitability. Using Ca2+ imaging, glutamate uncaging, fluorescence recovery after photobleaching and transgenic mice expressing labeled PSD-95, we comparatively analyzed electrical and Ca2+ signaling in spines and shaft synapses of dopamine neurons. Dendritic spines were present on dopaminergic neurons at low densities in live and fixed tissue. Uncaging-evoked potential amplitudes correlated inversely with spine length but positively with the presence of PSD-95. Spine Ca2+ signals were less sensitive to hyperpolarization than shaft synapses, suggesting amplification of spine head voltages. Lastly, activating spines during pacemaking, we observed an unexpected enhancement of spine Ca2+ midway throughout the spike cycle, likely involving recruitment of NMDA receptors and voltage-gated conductances. These results demonstrate functionality of spines in dopamine neurons and reveal a novel modulation of spine Ca2+ signaling during pacemaking.

Gut Microbiota and Cardiovascular Disease: Symbiosis Versus Dysbiosis

2021 ◽  
Vol 28 ◽  
Author(s):  
Antonis A. Manolis ◽  
Theodora A. Manolis ◽  
Helen Melita ◽  
Antonis S. Manolis
Keyword(s):  
Blood Circulation ◽  
Inflammatory Responses ◽  
Short Chain Fatty Acids ◽  
Therapeutic Interventions ◽  
Bile Acid Metabolism ◽  
Gi Tract ◽  
System A ◽  
Increased Risk ◽  
And Function ◽  
Potential Use

: The gut microbiome interacts with host physiology through various mechanisms, including the cardiovascular (CV) system. A healthy microbiome has the ability to process and digest complex carbohydrates into short-chain fatty acids (SCFA). These SCFA function as signaling molecules, immune-modulating molecules, and energy sources. However, when the microbiome is altered, it produces gut dysbiosis with overgrowth of certain bacteria that may lead to overproduction of trimethylamine-N-oxide (TMAO) from the metabolism of phosphatidylcholine, choline, and carnitine; dysbiosis also leads to increased intestinal permeability allowing the microbiome-derived lipopolysaccharide (LPS), a bacterial endotoxin, to enter the blood circulation triggering inflammatory responses. An altered GI tract environment and microbiome-derived metabolites are associated with CV events. Disrupted content and function of the microbiome leading to elevated TMAO and LPS levels, altered bile acid metabolism pathways and SCFA production, is associated with an increased risk of CV diseases (CVD), including atherosclerosis, myocardial infarction, thrombosis, arrhythmias and stroke. Therapeutic interventions that may favorably influence a dysbiotic GI tract profile and promote a healthy microbiome may benefit the CV system and lead to a reduction of CVD incidence in certain situations. These issues are herein reviewed with a focus on the spectrum of microbiota-related CVD, the mechanisms involved and the potential use of microbiome modification as a possible therapeutic intervention.

Particular subpopulations of midbrain and hypothalamic dopamine neurons express vesicular glutamate transporter 2 in the rat brain

2006 ◽  
Vol 498 (5) ◽  
pp. 581-592 ◽  
Author(s):  
Michihiro Kawano ◽  
Akiko Kawasaki ◽  
Hiromi Sakata-Haga ◽  
Yoshihiro Fukui ◽  
Hitoshi Kawano ◽  
...  
Keyword(s):  
Rat Brain ◽  
Glutamate Transporter ◽  
Dopamine Neurons ◽  
Vesicular Glutamate Transporter ◽  
Hypothalamic Dopamine

scholarly journals Developmental and Target-Dependent Regulation of Vesicular Glutamate Transporter Expression by Dopamine Neurons

2008 ◽  
Vol 28 (25) ◽  
pp. 6309-6318 ◽  
Author(s):  
J. A. Mendez ◽  
M.-J. Bourque ◽  
G. D. Bo ◽  
M. L. Bourdeau ◽  
M. Danik ◽  
...  
Keyword(s):  
Glutamate Transporter ◽  
Dopamine Neurons ◽  
Vesicular Glutamate Transporter ◽  
Transporter Expression

scholarly journals Hypophysiotropic Thyrotropin-Releasing Hormone and Corticotropin-Releasing Hormone Neurons of the Rat Contain Vesicular Glutamate Transporter-2

Endocrinology ◽  
2005 ◽  
Vol 146 (1) ◽  
pp. 341-347 ◽  
Author(s):  
Erik Hrabovszky ◽  
Gábor Wittmann ◽  
Gergely F. Turi ◽  
Zsolt Liposits ◽  
Csaba Fekete
Keyword(s):  
Glutamate Release ◽  
Glutamate Transporter ◽  
Microscopic Analysis ◽  
Male Rat ◽  
Confocal Laser ◽  
Vesicular Glutamate Transporter ◽  
Releasing Hormone ◽  
Large Numbers ◽  
Adult Male Rat ◽  
Dual Label

TRH and CRH are secreted into the hypophysial portal circulation by hypophysiotropic neurons located in parvicellular subdivisions of the hypothalamic paraventricular nucleus (PVH). Recently these anatomical compartments of the PVH have been shown to contain large numbers of glutamatergic neurons expressing type 2 vesicular glutamate transporter (VGLUT2). In this report we presented dual-label in situ hybridization evidence that the majority (>90%) of TRH and CRH neurons in the PVH of the adult male rat express the mRNA encoding VGLUT2. Dual-label immunofluorescent studies followed by confocal laser microscopic analysis of the median eminence also demonstrated the occurrence of VGLUT2 immunoreactivity within TRH and CRH axon varicosities, suggesting terminal glutamate release from these neuroendocrine systems. These data together indicate that the hypophysiotropic TRH and CRH neurons possess glutamatergic characteristics. Future studies will need to address the physiological significance of the endogenous glutamate content in these neurosecretory systems in the neuroendocrine regulation of thyroid and adrenal functions.

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