Topics

Cell-Genotype Specific Effects of Mecp2 Mutation on Spontaneous and Nicotinic Acetylcholine Receptor-Evoked Currents in Medial Prefrontal Cortical Pyramidal Neurons in Female Rett Model Mice.

08:00 EDT 9th July 2019 | BioPortfolio

Summary of "Cell-Genotype Specific Effects of Mecp2 Mutation on Spontaneous and Nicotinic Acetylcholine Receptor-Evoked Currents in Medial Prefrontal Cortical Pyramidal Neurons in Female Rett Model Mice."

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene. Random X-inactivation produces a mosaic of mutant (MT) and wild-type (WT) neurons in female Mecp2+/- (het) mice. Many RTT symptoms are alleviated by increasing activity in medial prefrontal cortex (mPFC) in RTT model mice (Howell et al., 2017). Using a GFP-MeCP2 fusion protein to distinguish WT from MT pyramidal neurons in mPFC we found cell autonomous (cell genotype specific) and non-autonomous effects of MeCP2 deficiency on spontaneous excitatory/inhibitory balance, nicotinic acetylcholine receptor (nAChR) currents and evoked activity. MT Layer 5 and 6 (L5, L6) neurons of male nulls, and MT L6 of het mice had reduced spontaneous excitatory synaptic input compared to WT in wild-type male (WTm), female (WTf) and het mice. Inhibitory synaptic charge in MT L6 equaled WT in 2-4-month hets. At 6-7 months inhibitory charge in WT in het slices was increased compared to both MT in het and WT in WTf; however, in hets the excitatory/inhibitory charge ratio was still greater in WT compared to MT. nAChR currents were reduced in L6 of nulls and MT L6 in het slices compared to WT neurons of het, WTm and WTf. At 2-4 months, ACh perfusion increased frequency of inhibitory currents to L6 neurons equally in all genotypes but increased excitatory inputs to MT and WT in hets less than WT in WTfs. Unexpectedly ACh perfusion evoked greater sustained IPSC and EPSC input to L5 neurons of nulls compared to WTm.

Affiliation

Journal Details

This article was published in the following journal.

Name: Neuroscience
ISSN: 1873-7544
Pages:

Links

DeepDyve research library

PubMed Articles [38599 Associated PubMed Articles listed on BioPortfolio]

P152R Mutation Within MeCP2 Can Cause Loss of DNA-Binding Selectivity.

MeCP2 is a protein highly expressed in the brain that participates in the genetic expression and RNA splicing regulation. MeCP2 binds preferably to methylated DNA and other nuclear corepressors to alt...

Accelerated Hyper-Maturation of Parvalbumin Circuits in the Absence of MeCP2.

Methyl-CpG-binding protein 2 (MeCP2) mutations are the primary cause of Rett syndrome, a severe neurodevelopmental disorder. Cortical parvalbumin GABAergic interneurons (PV) make exuberant somatic con...

MeCP2 promotes endothelial-to-mesenchymal transition in human endothelial cells by downregulating BMP7 expression.

Endothelial-to-mesenchymal transition (EndMT) plays a pivotal role in the development of organ fibrosis and can be induced by TGF-β. It is characterized by the loss of endothelial cell markers and th...

Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex.

Nicotine activates nicotinic acetylcholine receptors and improves cognitive and sensory function, in part by its actions in cortical regions. Physiological studies show that nicotine amplifies stimulu...

Intraspecific Variation in Microsatellite Mutation Profiles in Daphnia magna.

Microsatellite loci (tandem repeats of short nucleotide motifs) are highly abundant in eukaryotic genomes and often used as genetic markers because they can exhibit variation both within and between p...

Clinical Trials [14601 Associated Clinical Trials listed on BioPortfolio]

Biobanking of Rett Syndrome and Related Disorders

The overarching purpose of this study is to advance understanding of the natural history of Rett syndrome (RTT), MECP2-duplication disorder (MECP2 Dup), RTT-related disorders including CDK...

Rare Diseases Clinical Research Network: Neurophysiological Correlates

The overall purpose of this project is to advance understanding of the neurophysiological features of Rett syndrome (RTT), MECP2 Duplication (MECP2 Dup) and RTT-related disorders (CDKL5, F...

The Effectiveness of Kuvan in Amish PKU Patients

The purpose of this study is to determine if Amish patients with PKU show responsiveness after a high dose, prolonged Saproterin trial. The population of interest has a high frequency of a...

Effect of Nicotinic Acid on Adipose Tissue Inflammation in Obese Subjects

Our working hypothesis postulates that lipolysis is a determinant of inflammation in adipose tissue (AT). Inhibition of lipolysis, e.g. using the oldest normolipidemic drug, nicotinic acid...

PET Study of the Nicotinic Receptors in Human

The purpose of this study is to quantify the brain distribution of the nicotinic receptors in human volunteers and their alterations in patients suffering from neurological diseases such a...

Medical and Biotech [MESH] Definitions

Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).

Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.

Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.

Concept which describes the incremental effects of MUTATION in living organisms.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

Quick Search


DeepDyve research library

Relevant Topic

Bioinformatics
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...


Searches Linking to this Article