Physiology is a wide spanning discipline, and it is interesting to follow its journey into the unknown in different organs, and with ever more sophisticated methods. This research is reflected by high quality publications in physiological journals. Have a look!
The results of this research as well as of comparative physiology and mathematical modelling, provide ever growing insight into the body’s functions, mechanisms of disease and new therapies, including gene therapy and development of vaccines. The close interaction between basic physiological research and clinical work, has improved human health and life span and holds even more promises for the future.
A most interesting aspect of current physiology is that, unlike in past centuries, novel models and techniques have reduced or replaced the need to destroy or dissect organs and tissues to improve understanding of function. Now we can learn from growing cells and stimulating them to form tissues and even “organs”. It has become almost routine for physiologists to manipulate gene expression to study function in the intact animal. We are obtaining novel and unique insights into the principles of self-organisation of cells and their mutual interactions. Exciting times, indeed!
Physiology is a wide spanning discipline, and it is interesting to follow its journey into the unknown in different organs, and with ever more sophisticated methods. This research is reflected by high quality publications in physiological journals. Have a look!
Yun-Ju Fang et al.
Maternal exercise may influence long-term cardiovascular health in offspring, yet its effects on intrinsic myocardial performance and mitochondrial metabolism remain incompletely defined.
NEW & NOTEWORTHY Maternal voluntary exercise before and during pregnancy was associated with altered load-independent systolic reserve and substrate-dependent mitochondrial respiratory adaptations in adult offspring, with the clearest and most interpretable phenotype observed in females. Female offspring from exercise dams showed greater dobutamine-induced recruitment of end-systolic elastance together with changes in mitochondrial respiratory control. These findings suggest that maternal exercise may produce persistent functional and metabolic adaptations in the adult offspring heart.
Christelinda Laureijs and Karen M. Crosby
NEW & NOTEWORTHY Although insulin is well known for regulating blood glucose levels and energy metabolism, its role in the dorsomedial hypothalamus (DMH) is not well understood. This study shows that insulin reduces glutamatergic transmission in the DMH of both sexes, through both insulin receptors and insulin-like growth factor 1 receptors. Endogenous insulin also decreases glutamate transmission, primarily through insulin receptors. These findings demonstrate insulin’s actions at a key site of appetite regulation and energy metabolism.
Aaron A. Jones et al.
Circadian clock protein Bmal1 regulates respiratory motor plasticity in male rats
Acute intermittent hypoxia (AIH) elicits respiratory motor plasticity in the phrenic, intercostal, and hypoglossal motor pools and has emerged as a promising therapeutic strategy to improve respiratory function in people with neuromuscular disorders that compromise breathing.
NEW & NOTEWORTHY Although diurnal cycle influences respiratory motor plasticity elicited by acute intermittent hypoxia (AIH), it is unknown how endogenous circadian clock mechanisms contribute to time-of-day effects on plasticity. We report that knockdown of the circadian clock protein Bmal1 within respiratory motor neurons attenuates phrenic and ventilatory long-term facilitation in a manner dependent on diurnal phase. Thus, circadian biology is an important consideration for studies of respiratory motor plasticity.
Much more can be found in this month’s selection of articles from APS journals!
These new and engaging video feature from The Journal of Physiology aims to deliver short and informative research snapshots directly from the authors of research papers selected by the Editors of the journal!
You will find the “Science Topics” on the main page, scrolling down to “News” and clicking “Science Topics”.
The latest topic relates to an article published by Hirohito Kuno et al in Cell Reports: Intralaminar thalamus relays basal ganglia output to the insular cortex to drive tic generation
Significance
The authors have demonstrated that the basal ganglia-intralaminar thalamo-insular pathway plays an important role in the generation of tics, using a mouse model that exhibits prominent tic-like movements. Tic disorders are characterized by sudden, repetitive movements (“motor tics”) and vocalizations including inappropriate words or sounds (“vocal tics”). Many patients experience unpleasant sensations that precede tics, known as premonitory urges, and frequently have comorbid psychiatric conditions such as obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). These clinical features suggest that tic disorders arise from dysfunction beyond motor brain regions. Instead, brain areas involved in uncomfortable internal sensations and emotional processing may also contribute to the pathophysiology of tics. However, the underlying neuronal mechanisms have remained unclear.
Our study revealed that the intralaminar thalamic nuclei connect motor domains of the basal ganglia to the insular cortex, a brain region involved in sensory and emotional processing. We further showed that chemogenetic inhibition of the intralaminar thalamo-insular pathway in the tic mouse model reduced tic-like movements and abnormal neuronal activities associated with tics. These findings provide new insight into the neuronal mechanisms underlying tic disorders and can contribute to the future development of novel therapeutic strategies
DPG’s latest paper of the month (Johanna K Freundt et al) was recently published in Nat Cardiovasc Res
Selective titin cleavage disrupts cardiac mechanical homeostasis to drive heart failure and fibrosis
From the abstract:Titin, the largest human protein, forms the elastic sarcomeric backbone, providing passive stiffness and length-dependent activation in cardiomyocytes. Whereas titin mutations cause inherited cardiomyopathies, ischemic and chemotherapy-induced injury also provoke proteolytic cleavage of titin’s elastic segment. However, the effects of acute titin stiffness loss remain unknown. Here we develop a knock-in mouse enabling in vivo cleavage of cardiac titin springs and use multimodal analysis (cardiac magnetic resonance imaging, echocardiography, microscopy, omics) to show that titin cleavage does not dilate the heart but reduces chamber size and impairs ventricular filling. Mechanical assays of isolated cardiomyocytes reveal diminished restoring forces causing a loss of elastic recoil. In vivo cleavage disrupts junctions, including integrin linkages and connexin 43 gap junctions, widens intermyocyte space without hypertrophy or hyperplasia and drives fibroblast activation, extracellular matrix remodeling and fibrosis. Compensatory mechanisms fail, leading to decompensated heart failure. These findings establish that proteolytic titin cleavage perturbs cardiac mechanical homeostasis, driving disease and matrix stiffening.