Expression data from WT and VAChT KDHOM whole hearts
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31395 | GEO | 2012/08/15
SECONDARY ACCESSION(S): PRJNA145881
REPOSITORIES: GEO
Similar Datasets
Project description:VAChT KDHOM mice have a 70% decrease in the vesicular acetylcholine transporter (VAChT) and this leads to a systemic decrease in ACh release and cardiac dysfunction. We used this microarray to determine whether there were transcriptional alterations in the hearts of mutant mice as a result of this long-term decrease in cholinergic tone.
2012-11-14 | GSE37458 | GEO
Project description:VAChT KDHOM mice have a 70% decrease in the vesicular acetylcholine transporter (VAChT) and this leads to a systemic decrease in ACh release and cardiac dysfunction. We used this microarray to determine whether there were transcriptional alterations in the hearts of mutant mice as a result of this long-term decrease in cholinergic tone. We isolated whole hearts from 3-month-old WT and VAChT KD mice and used them for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogenous populations for each sample and, as such, pooled together two RNA samples to generate one microarray sample.
2012-11-14 | E-GEOD-37458 | biostudies-arrayexpress
Project description:Background: Stress exacerbates symptoms of schizophrenia and attention deficit hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. Here we investigated whether a 6-day variable stressor (VS) altered sustained attention and the cholinergic attention system in male and female rats. Methods: Sustained attention was tested with the sustained attention task (SAT). Successful performance on SAT relies on the release of acetylcholine (ACh) into the cortex from cholinergic neurons in the nucleus basalis of Meynert (NBM). Thus, we evaluated whether VS altered the morphology of these neurons with a novel approach using Cre-dependent virus in genetically modified ChAT::Cre rats, a species used for this manipulation only. Next, electrochemical recordings measured cortical ACh following VS. Finally, we used RNAseq to identify VS-induced transcriptional changes in the NBM. Results: VS impaired attentional performance in SAT and increased the dendritic complexity of NBM cholinergic neurons in both sexes. NBM cholinergic neurons are mainly under inhibitory control, so this morphological change could increase inhibition on these neurons, reducing downstream ACh release to impair attention. Indeed, VS decreased ACh release in the prefrontal cortex of males. Quantification of global transcriptional changes revealed that, although VS induced many sex-specific changes in gene expression, it increased several signaling molecules in both sexes.
2020-05-01 | GSE147806 | GEO
Project description:Acetylcholine (ACh) has been considered a neurotransmitter residing in central, parasympathetic and neuromuscular synapses of mammals. Here, experiments using crypt-villus organoids that lack nerve and immune cells in culture led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). The extracts of the cultured organoids exhibit a noticeable capacity for ACh synthesis that is sensitive to a potent inhibitor of choline acetyltransferase (ChAT). Imaging mass spectrometry reveals distribution of endogenous ACh that is localized in intestinal epithelial layer in the cultured organoids as well as in mouse small intestinal epithelium in vivo, suggesting non-neural resources of ACh. Treatment of organoids with carbachol down-regulates growth of organoids and expression of marker gene for each epithelial cell. On the other hand, antagonists for mAChRs enhances growth and differentiation of organoids, indicating involvement of mAChRs in regulating proliferation and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from intestinal epithelium maintains homeostasis of intestinal epithelial cell growth and differentiation via mAChRs in mice. Gene expression patters of gut, crypt, y-organoid and o-organoid, respectively
2013-08-15 | E-GEOD-49864 | biostudies-arrayexpress
Project description:Acetylcholine (ACh) has been considered a neurotransmitter residing in central, parasympathetic and neuromuscular synapses of mammals. Here, experiments using crypt-villus organoids that lack nerve and immune cells in culture led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). The extracts of the cultured organoids exhibit a noticeable capacity for ACh synthesis that is sensitive to a potent inhibitor of choline acetyltransferase (ChAT). Imaging mass spectrometry reveals distribution of endogenous ACh that is localized in intestinal epithelial layer in the cultured organoids as well as in mouse small intestinal epithelium in vivo, suggesting non-neural resources of ACh. Treatment of organoids with carbachol down-regulates growth of organoids and expression of marker gene for each epithelial cell. On the other hand, antagonists for mAChRs enhances growth and differentiation of organoids, indicating involvement of mAChRs in regulating proliferation and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from intestinal epithelium maintains homeostasis of intestinal epithelial cell growth and differentiation via mAChRs in mice.
2013-08-15 | GSE49864 | GEO
Project description:Nair2015 - Interaction between
neuromodulators via GPCRs - Effect on cAMP/PKA signaling (D2
Neuron)
This model is described in the article:
Sensing Positive versus
Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs
in Direct and Indirect Pathway Striatal Medium Spiny
Neurons.
Nair AG, Gutierrez-Arenas O,
Eriksson O, Vincent P, Hellgren Kotaleski J.
J. Neurosci. 2015 Oct; 35(41):
14017-14030
Abstract:
Transient changes in striatal dopamine (DA) concentration
are considered to encode a reward prediction error (RPE) in
reinforcement learning tasks. Often, a phasic DA change occurs
concomitantly with a dip in striatal acetylcholine (ACh),
whereas other neuromodulators, such as adenosine (Adn), change
slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs
for these neuromodulators in striatal medium spiny neurons
(MSNs), which play important roles in plasticity. However,
little is known about the interaction between these
neuromodulators via GPCRs. The interaction between these
transient neuromodulator changes and the effect on cAMP/PKA
signaling via Golf- and Gi/o-coupled GPCR are studied here
using quantitative kinetic modeling. The simulations suggest
that, under basal conditions, cAMP/PKA signaling could be
significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an
ACh dip is required to gate a subset of D1R/Golf-dependent PKA
activation. Furthermore, the interaction between ACh dip and DA
peak, via D1R and M4R, is synergistic. In a similar fashion,
PKA signaling in D2+ MSNs is under basal inhibition via
D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting
A2aR/Golf, but D2+ MSNs could also respond to the DA peak via
other intracellular pathways. This study highlights the
similarity between the two types of MSNs in terms of high basal
AC inhibition by Gi/o and the importance of interactions
between Gi/o and Golf signaling, but at the same time predicts
differences between them with regard to the sign of RPE
responsible for PKA activation.Dopamine transients are
considered to carry reward-related signal in reinforcement
learning. An increase in dopamine concentration is associated
with an unexpected reward or salient stimuli, whereas a
decrease is produced by omission of an expected reward. Often
dopamine transients are accompanied by other neuromodulatory
signals, such as acetylcholine and adenosine. We highlight the
importance of interaction between acetylcholine, dopamine, and
adenosine signals via adenylyl-cyclase coupled GPCRs in shaping
the dopamine-dependent cAMP/PKA signaling in striatal neurons.
Specifically, a dopamine peak and an acetylcholine dip must
interact, via D1 and M4 receptor, and a dopamine dip must
interact with adenosine tone, via D2 and A2a receptor, in
direct and indirect pathway neurons, respectively, to have any
significant downstream PKA activation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000636.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000636 | BioModels
Project description:Nair2015 - Interaction between
neuromodulators via GPCRs - Effect on cAMP/PKA signaling (D1
Neuron)
This model is described in the article:
Sensing Positive versus
Negative Reward Signals through Adenylyl Cyclase-Coupled GPCRs
in Direct and Indirect Pathway Striatal Medium Spiny
Neurons.
Nair AG, Gutierrez-Arenas O,
Eriksson O, Vincent P, Hellgren Kotaleski J.
J. Neurosci. 2015 Oct; 35(41):
14017-14030
Abstract:
Transient changes in striatal dopamine (DA) concentration
are considered to encode a reward prediction error (RPE) in
reinforcement learning tasks. Often, a phasic DA change occurs
concomitantly with a dip in striatal acetylcholine (ACh),
whereas other neuromodulators, such as adenosine (Adn), change
slowly. There are abundant adenylyl cyclase (AC) coupled GPCRs
for these neuromodulators in striatal medium spiny neurons
(MSNs), which play important roles in plasticity. However,
little is known about the interaction between these
neuromodulators via GPCRs. The interaction between these
transient neuromodulator changes and the effect on cAMP/PKA
signaling via Golf- and Gi/o-coupled GPCR are studied here
using quantitative kinetic modeling. The simulations suggest
that, under basal conditions, cAMP/PKA signaling could be
significantly inhibited in D1R+ MSNs via ACh/M4R/Gi/o and an
ACh dip is required to gate a subset of D1R/Golf-dependent PKA
activation. Furthermore, the interaction between ACh dip and DA
peak, via D1R and M4R, is synergistic. In a similar fashion,
PKA signaling in D2+ MSNs is under basal inhibition via
D2R/Gi/o and a DA dip leads to a PKA increase by disinhibiting
A2aR/Golf, but D2+ MSNs could also respond to the DA peak via
other intracellular pathways. This study highlights the
similarity between the two types of MSNs in terms of high basal
AC inhibition by Gi/o and the importance of interactions
between Gi/o and Golf signaling, but at the same time predicts
differences between them with regard to the sign of RPE
responsible for PKA activation.Dopamine transients are
considered to carry reward-related signal in reinforcement
learning. An increase in dopamine concentration is associated
with an unexpected reward or salient stimuli, whereas a
decrease is produced by omission of an expected reward. Often
dopamine transients are accompanied by other neuromodulatory
signals, such as acetylcholine and adenosine. We highlight the
importance of interaction between acetylcholine, dopamine, and
adenosine signals via adenylyl-cyclase coupled GPCRs in shaping
the dopamine-dependent cAMP/PKA signaling in striatal neurons.
Specifically, a dopamine peak and an acetylcholine dip must
interact, via D1 and M4 receptor, and a dopamine dip must
interact with adenosine tone, via D2 and A2a receptor, in
direct and indirect pathway neurons, respectively, to have any
significant downstream PKA activation.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000635.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000635 | BioModels
Project description:Ehrenstein2000 - Positive-Feedback model for
the loss of acetylcholine in Alzheimer's disease
Curated model derived from
BIOMD0000000553
This model is described in the article:
A positive-feedback model
for the loss of acetylcholine in Alzheimer's disease.
Ehrenstein G, Galdzicki Z, Lange
GD.
Ann. N. Y. Acad. Sci. 2000; 899:
283-291
Abstract:
We describe a two-component positive-feedback system that
could account for the large reduction of acetylcholine that is
characteristic of patients with Alzheimer's disease (AD). One
component is beta-amyloid-induced apoptosis of cholinergic
cells, leading to a decrease in acetylcholine. The other
component is an increase in the concentration of beta-amyloid
in response to a decrease in acetylcholine. We describe each
mechanism with a differential equation, and then solve the two
equations numerically. The solution provides a description of
the time course of the reduction of acetylcholine in AD
patients that is consistent with epidemiological data. This
model may also provide an explanation for the significant, but
lesser, decrease of other neurotransmitters that is
characteristic of AD.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000552.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2024-09-02 | BIOMD0000000552 | BioModels
Project description:Group 2 innate lymphoid cells (ILC2s) reside in multiple tissues including lymphoid organs and barrier surfaces, and secrete type 2 cytokines including interleukin (IL)-5, IL-9 and IL-13. These cells participate in multiple physiological processes including allergic inflammation, tissue repair, metabolic homeostasis and host defense against helminth infections. Recent studies indicate that neuropeptides can play an important role in regulating ILC2 responses, however, the mechanisms that underlie these processes in vivo remain incompletely defined. Here, we identify that activated ILC2s upregulate choline acetyltransferase (ChAT)—the enzyme responsible for the biosynthesis of acetylcholine (ACh)—following infection with the helminth parasite Nippostrongylus brasiliensis or treatment with alarmins or cytokines including IL-25, IL-33 and thymic stromal lymphopoietin (TSLP). ILC2s also express acetylcholine receptors (AChRs), and ACh administration promotes ILC2 cytokine production and elicits expulsion of helminth infection. In accordance with this, ChAT deficiency in ILC2s leads to defective ILC2 responses and impaired immunity against helminth infection. Together, these results reveal a previously unrecognized role of the ChAT-ACh pathway in promoting type 2 innate immunity to helminth infection.
2021-03-05 | GSE164705 | GEO
Project description:MicroRNAs (miRs) contribute to both neuronal and immune cell fate, but their involvement in inter-tissue communication remained unexplored. The brain, via vagal secretion of acetylcholine (ACh), suppresses peripheral inflammation by intercepting cytokine production; therefore, we predicted that microRNAs targeting acetylcholinesterase (AChE) can attenuate inflammation. Here, we report that inflammatory stimuli induce leukocyte over-expression of the AChE-targeting miR-132. Injected LNA-modified anti-miR-132 oligonucleotide depleted miR-132 levels while elevating AChE in mouse circulation and tissues. In transfected cells, a mutated 3’UTR miR-132 binding site increased AChE mRNA expression, whereas cells infected with a lentivirus expressing pre-miR-132 showed suppressed AChE. Transgenic mice over-expressing 3'UTR-null AChE showed excessive inflammatory mediators and impaired cholinergic anti-inflammatory regulation, in spite of substantial miR-132 up-regulation in brain and bone marrow. Our findings identify the AChE mRNA-targeting miR-132 as a functional regulator of the brain-to-body resolution of inflammation, opening new avenues for study and therapeutic manipulations of the neuro-immune dialogue.
2009-11-24 | GSE19094 | GEO