Lipin1 as a therapeutic target for respiratory insufficiency of duchenne muscular dystrophy.

In Duchenne muscular dystrophy (DMD), diaphragm muscle dysfunction results in respiratory insufficiency which is a leading cause of death in patients. Mutations to the dystrophin gene result in myocyte membrane instability, contributing to the structural deterioration of the diaphragm muscle tissues. With previous works suggesting the importance of lipin1 for maintaining skeletal muscle membrane integrity, we explored the roles of lipin1 in the dystrophic diaphragm.

Pharmacological and behavioural effects of tryptamines present in psilocybin-containing mushrooms.

Background And Purpose: Demand for new antidepressants has resulted in a re-evaluation of the therapeutic potential of psychedelic drugs. Several tryptamines found in psilocybin-containing "magic" mushrooms share chemical similarities with psilocybin. Early work suggests they may share biological targets.

Differential consumption of alcohol, caffeine, and caffeinated alcohol by adolescent rats, and effects on post-adolescent gene expression signatures in the nucleus accumbens and orbitofrontal cortex.

Caffeinated alcoholic beverages (CABs) are widely consumed despite little known about their behavioral and biological effects. Furthermore, CABs are also popular among adolescents, a particularly vulnerable and maturing demographic. In this preliminary study, we compared levels of daily adolescent voluntary consumption of caffeine (0.

Acute Oxygen-Sensing Mitochondria-Generated Temperature Transients in Rat Carotid Body Type I Cells.

The Carotid Bodies (CB) are peripheral chemoreceptors that detect changes in arterial oxygenation and, via afferent inputs to the brainstem, correct the pattern of breathing to restore blood gas homeostasis. Herein, preliminary evidence is presented supporting a novel oxygen-sensing hypothesis which suggests CB Type I cell "hypoxic signaling" may in part be mediated by mitochondria-generated thermal transients in TASK-channel-containing microdomains. Distances were measured between antibody-labeled mitochondria and TASK-potassium channels in primary rat CB Type I cells.

High Fat Feeding in Rats Alters Respiratory Parameters by a Mechanism That Is Unlikely to Be Mediated by Carotid Body Type I Cells.

The carotid bodies (CB) respond to changes in blood gases with neurotransmitter release, thereby increasing carotid sinus nerve firing frequency and ultimately correcting the pattern of breathing. It has previously been demonstrated that acute application of the adipokine leptin augments the hypoxic sensory response of the intact in-vitro CB (Pye RL, Roy A, Wilson RJ, Wyatt CN. FASEB J 30(1 Supplement):983.

Acute oxygen sensing by the carotid body: a rattlebag of molecular mechanisms.

The molecular underpinnings of the oxygen sensitivity of the carotid body Type I cells are becoming better defined as research begins to identify potential interactions between previously separate theories. Nevertheless, the field of oxygen chemoreception still presents the general observer with a bewildering array of potential signalling pathways by which a fall in oxygen levels might initiate Type I cell activation. The purpose of this brief review is to address five of the current oxygen sensing hypotheses: the lactate-Olfr 78 hypothesis of oxygen chemotransduction; the role mitochondrial ATP and metabolism may have in chemotransduction; the AMP-activated protein kinase hypothesis and its current role in oxygen sensing by the carotid body; reactive oxygen species as key transducers in the oxygen sensing cascade; and the mechanisms by which H S, reactive oxygen species and haem oxygenase may integrate to provide a rapid oxygen sensing transduction system.