Mobilisation of jerboa kidney gene networks during dehydration and opportunistic rehydration.

Desert animals have evolved systems that enable them to thrive under dry conditions. Focusing on the kidney, we have investigated the transcriptomic adaptations that enable a desert rodent, the Lesser Egyptian Jerboa (), to withstand water deprivation and opportunistic rehydration. Analysis of the whole kidney transcriptome showed many differentially expressed genes in the Jerboa kidney, 6.

Transcriptomics of the Carotid Body.

The carotid body (CB) has emerged as a potential therapeutic target for treating sympathetically mediated cardiovascular, respiratory, and metabolic diseases. In adjunct to its classical role as an arterial O sensor, the CB is a multimodal sensor activated by a range of stimuli in the circulation. However, consensus on how CB multimodality is achieved is lacking; even the best studied O-sensing appears to involve multiple convergent mechanisms.

Isoflurane Rapidly Modifies Synaptic and Cytoskeletal Phosphoproteomes of the Supraoptic Nucleus of the Hypothalamus and the Cortex.

Introduction: Despite the widespread use of general anaesthetics, the mechanisms mediating their effects are still not understood. Although suppressed in most parts of the brain, neuronal activity, as measured by FOS activation, is increased in the hypothalamic supraoptic nucleus (SON) by numerous general anaesthetics, and evidence points to this brain region being involved in the induction of general anaesthesia (GA) and natural sleep. Posttranslational modifications of proteins, including changes in phosphorylation, enable fast modulation of protein function which could be underlying the rapid effects of GA.

Ageing restructures the transcriptome of the hypothalamic supraoptic nucleus and alters the response to dehydration.

Ageing is associated with altered neuroendocrine function. In the context of the hypothalamic supraoptic nucleus, which makes the antidiuretic hormone vasopressin, ageing alters acute responses to hyperosmotic cues, rendering the elderly more susceptible to dehydration. Chronically, vasopressin has been associated with numerous diseases of old age, including type 2 diabetes and metabolic syndrome.

Translational and Posttranslational Dynamics in a Model Peptidergic System.

The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus, whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses to neuronal stimulation are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt.

Carotid body: an emerging target for cardiometabolic co-morbidities.

New Findings: What is the topic of this review? Regarding the global metabolic syndrome crisis, this review focuses on common mechanisms for high blood sugar and high blood pressure. Connections are made between the homeostatic regulation of blood pressure and blood sugar and their dysregulation to reveal signalling mechanisms converging on the carotid body. What advances does it highlight? The carotid body plays a major part in the generation of excessive sympathetic activity in diabetes and also underpins diabetic hypertension.

Reproducing extracellular matrix adverse remodelling of non-ST myocardial infarction in a large animal model.

The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for an investigation into therapeutics and interventions directed at this subset of MI.

Transcriptomic plasticity of the hypothalamic osmoregulatory control centre of the Arabian dromedary camel.

Water conservation is vital for life in the desert. The dromedary camel (Camelus dromedarius) produces low volumes of highly concentrated urine, more so when water is scarce, to conserve body water. Two hormones, arginine vasopressin and oxytocin, both produced in the supraoptic nucleus, the core hypothalamic osmoregulatory control centre, are vital for this adaptive process, but the mechanisms that enable the camel supraoptic nucleus to cope with osmotic stress are not known.

Cellular basis of learning and memory in the carotid body.

The carotid body is the primary peripheral chemoreceptor in the body, and critical for respiration and cardiovascular adjustments during hypoxia. Yet considerable evidence now implicates the carotid body as a multimodal sensor, mediating the chemoreflexes of a wide range of physiological responses, including pH, temperature, and acidosis as well as hormonal, glucose and immune regulation. How does the carotid body detect and initiate appropriate physiological responses for these diverse stimuli? The answer to this may lie in the structure of the carotid body itself.

GLP1R Attenuates Sympathetic Response to High Glucose via Carotid Body Inhibition.

Background: Aberrant sympathetic nerve activity exacerbates cardiovascular risk in hypertension and diabetes, which are common comorbidities, yet clinically sympathetic nerve activity remains poorly controlled. The hypertensive diabetic state is associated with increased reflex sensitivity and tonic drive from the peripheral chemoreceptors, the cause of which is unknown. We have previously shown hypertension to be critically dependent on the carotid body (CB) input in spontaneously hypertensive rat, a model that also exhibits a number of diabetic traits.

In the balance: how do thrombospondins contribute to the cellular pathophysiology of cardiovascular disease?

Thrombospondins (TSPs) are multidomain, secreted proteins that associate with cell surfaces and extracellular matrix. In mammals, there is a large body of data on functional roles of various TSP family members in cardiovascular disease (CVD), including stroke, cardiac remodeling and fibrosis, atherosclerosis, and aortic aneurysms. Coding single nucleotide polymorphisms (SNPs) of TSP1 or TSP4 are also associated with increased risk of several forms of CVD.

Corticosterone pattern-dependent glucocorticoid receptor binding and transcriptional regulation within the liver.

Ultradian glucocorticoid rhythms are highly conserved across mammalian species, however, their functional significance is not yet fully understood. Here we demonstrate that pulsatile corticosterone replacement in adrenalectomised rats induces a dynamic pattern of glucocorticoid receptor (GR) binding at ~3,000 genomic sites in liver at the pulse peak, subsequently not found during the pulse nadir. In contrast, constant corticosterone replacement induced prolonged binding at the majority of these sites.

Osmoregulation of the transcriptome of the hypothalamic supraoptic nucleus: A resource for the community.

The hypothalamic supraoptic nucleus (SON) is a core osmoregulatory control centre that deciphers information about the metabolic state of the organism and orchestrates appropriate homeostatic (endocrine) and allostatic (behavioural) responses. We have used RNA sequencing to describe the polyadenylated transcriptome of the SON of the male Wistar Han rat. These data have been mined to generate comprehensive catalogues of functional classes of genes (enzymes, transcription factors, endogenous peptides, G protein coupled receptors, transporters, catalytic receptors, channels and other pharmacological targets) expressed in this nucleus in the euhydrated state, and that together form the basal substrate for its physiological interactions.

Multiomic analysis of the Arabian camel (Camelus dromedarius) kidney reveals a role for cholesterol in water conservation.

The Arabian camel (Camelus dromedarius) is the most important livestock animal in arid and semi-arid regions and provides basic necessities to millions of people. In the current context of climate change, there is renewed interest in the mechanisms that enable camelids to survive in arid conditions. Recent investigations described genomic signatures revealing evolutionary adaptations to desert environments.

cAMP-dependent regulation of HCN4 controls the tonic entrainment process in sinoatrial node pacemaker cells.

It is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in the sinoatrial node (SAN) is involved in heart rate regulation by the autonomic nervous system. We addressed this question using a knockin mouse line expressing cyclic adenosine monophosphate-insensitive HCN4 channels. This mouse line displayed a complex cardiac phenotype characterized by sinus dysrhythmia, severe sinus bradycardia, sinus pauses and chronotropic incompetence.

Ultrastructural changes of the human enteric nervous system and interstitial cells of Cajal in diverticular disease.

Background: In spite of numerous advances in understanding diverticular disease, its pathogenesis remains one of the main problems to be solved. We aimed to investigate the ultrastructural changes of the enteric nervous system in unaffected individuals, in asymptomatic patients with diverticulosis and in patients with diverticular disease.

Methods: Transmission electron microscopy was used to analyse samples of the myenteric, outer submucosal and inner submucosal plexuses from patients without diverticula (n=9), asymptomatic patients with diverticulosis (n=7) and in patients with complicated diverticular disease (n=9).

Neuroanatomy of the Pig Cardiac Ventricles. A Stereomicroscopic, Confocal and Electron Microscope Study.

Although the pig is a model for heart disease, the neuroanatomy of cardiac ventricles (CV) in this species remains undetailed. We aimed to define the innervation pattern of pig CV, combining histochemistry for acetylcholinesterase, immunofluorescent labeling and electron microscopy. Forty nine examined pig hearts show that the major nerves supplying the ventral side of CV descend from the venous part of the heart hilum.

Innervation of the rabbit cardiac ventricles.

The rabbit is widely used in experimental cardiac physiology, but the neuroanatomy of the rabbit heart remains insufficiently examined. This study aimed to ascertain the architecture of the intrinsic nerve plexus in the walls and septum of rabbit cardiac ventricles. In 51 rabbit hearts, a combined approach involving: (i) histochemical acetylcholinesterase staining of intrinsic neural structures in total cardiac ventricles; (ii) immunofluorescent labelling of intrinsic nerves, nerve fibres (NFs) and neuronal somata (NS); and (iii) transmission electron microscopy of intrinsic ventricular nerves and NFs was used.

A combined acetylcholinesterase and immunohistochemical method for precise anatomical analysis of intrinsic cardiac neural structures.

A significant challenge when investigating autonomic neuroanatomy is being able to reliably obtain tissue that contains neuronal structures of interest. Currently, histochemical staining for acetylcholinesterase (AChE) remains the most feasible and reliable method to visualize intrinsic nerves and ganglia in whole organs. In order to precisely visualize and sample intrinsic cardiac nerves and ganglia for subsequent immunofluorescent labeling, we developed a modified histochemical AChE method using material from pig and sheep hearts.

Innervation of sinoatrial nodal cardiomyocytes in mouse. A combined approach using immunofluorescent and electron microscopy.

Fluorescent immunohistochemistry on the cardiac conduction system in whole mount mouse heart preparations demonstrates a particularly dense and complex network of nerve fibres and cardiomyocytes which are positive to the hyperpolarization activated cyclic nucleotide-gated potassium channel 4 (HCN4-positive cardiomyocytes) in the sinoatrial node region and adjacent areas around the root of right cranial vein. The present study was designed to investigate the morphologic and histochemical pattern of nerve fibres and HCN4-positive cardiomyocytes using fluorescent techniques and/or electron microscopy. Adrenergic and cholinergic nerve fibres together with HCN4-positive cardiomyocytes were identified using primary antibodies for tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), and the HCN4 channel respectively.

Morphological pattern of intrinsic nerve plexus distributed on the rabbit heart and interatrial septum.

Although the rabbit is routinely used as the animal model of choice to investigate cardiac electrophysiology, the neuroanatomy of the rabbit heart is not well documented. The aim of this study was to examine the topography of the intrinsic nerve plexus located on the rabbit heart surface and interatrial septum stained histochemically for acetylcholinesterase using pressure-distended whole hearts and whole-mount preparations from 33 Californian rabbits. Mediastinal cardiac nerves entered the venous part of the heart along the root of the right cranial vein (superior caval vein) and at the bifurcation of the pulmonary trunk.