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Full-Text Articles in Medicine and Health Sciences

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov Jan 2019

Forebrain Cholinergic Signaling Regulates Innate Immune Responses And Inflammation, Ashbeel Roy, Vania F. Prado, Marco A.M Prado, Robert Gros, Kurt R. Lehner, Harold A. Silvernman, Meghan E. Addorissio, Mohammed A. Al-Onaizi, Yaakov Levine, Peder S. Olofsson, Sangeeta S. Chavan, Neil M. Nathanson, Yousef Al-Abed, Christine N. Metz, Kevin J. Tracey, Valentin A. Pavlov

Anatomy and Cell Biology Publications

The brain regulates physiological functions integral to survival. However, the insight into brain neuronal regulation of peripheral immune function and the neuromediator systems and pathways involved remains limited. Here, utilizing selective genetic and pharmacological approaches, we studied the role of forebrain cholinergic signaling in the regulation of peripheral immune function and inflammation. Forebrain-selective genetic ablation of acetylcholine release and vagotomy abolished the suppression of serum TNF by the centrally-acting cholinergic drug galantamine in murine endotoxemia. Selective stimulation of acetylcholine action on the M1 muscarinic acetylcholine receptor (M1 mAChR) by central administration of the positive allosteric modulator benzyl quinolone carboxylic acid …


The Role Of Cholinergic Signaling In Cardiac Function, Rachel Reingold Sep 2018

The Role Of Cholinergic Signaling In Cardiac Function, Rachel Reingold

Electronic Thesis and Dissertation Repository

Cardiovascular disease is one of the leading causes of death in Canada. Treatment currently focuses on preventing the increase of sympathetic signaling seen in heart failure. However, it has recently been noted that cardiac function is dependent on parasympathetic tone. Previous studies have demonstrated the development of heart failure when cholinergic targets are knocked out in cardiomyocytes. Transgenic mouse models that have increased cholinergic transmission show protection against cardiovascular insults. We have shown that transgenic mice overexpressing vesicular acetylcholine transporter in cholinergic cells show cardiovascular protection in response to ex vivo insults. As well, this protection is seen when cholinergic …


Vacht Overexpression Increases Acetylcholine At The Synaptic Cleft And Accelerates Aging Of Neuromuscular Junctions, Satoshi Sugita, Leland L. Fleming, Caleb Wood, Sydney K. Vaughan, Matheus P. S. M. Gomes, Wallace Camargo, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim, Gregorio Valdez Oct 2016

Vacht Overexpression Increases Acetylcholine At The Synaptic Cleft And Accelerates Aging Of Neuromuscular Junctions, Satoshi Sugita, Leland L. Fleming, Caleb Wood, Sydney K. Vaughan, Matheus P. S. M. Gomes, Wallace Camargo, Ligia A. Naves, Vania F. Prado, Marco A. M. Prado, Cristina Guatimosim, Gregorio Valdez

Anatomy and Cell Biology Publications

Background: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age-and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS). Methods: Chat-ChR2-EYFP (VAChTHyp) mice containing multiple copies of the vesicular acetylcholine transporter (VAChT), mutant superoxide dismutase 1 (SOD1G93A), and Chat-IRES-Cre and tdTomato transgenic mice were used in this …