Laurent gautron

Activated microglia have been implicated in the pathogenesis of age-related macular degeneration (AMD), diabetic retinopathy, and other neurodegenerative and neuroinflammatory disorders, but our understanding of the mechanisms behind their activation is in infant stages. With the goal of identifying novel genes associated with microglial activation in the retina, we applied a semiquantitative fundus spot scoring scale to an unbiased, state-of-the-science mouse forward genetics pipeline. A mutation in the gene encoding the E3 ubiquitin ligase Herc3 led to prominent accumulation of fundus spots...

GPR149 is an orphan receptor about which little is known. Accordingly, in the present study, we mapped the tissue expression of Gpr149 in mice using three complementary approaches: quantitative PCR, in situ hybridization, and a newly generated Gpr149-Cre reporter mouse model. The strongest expressions of Gpr149 were observed in neurons of the islands of Calleja, the ventromedial hypothalamus, and the rostral interpeduncular nucleus. Moderate-to-low expression was also observed in the basal forebrain, striatum, hypothalamus, brainstem, and spinal cord...

The glucagon receptor (GCGR) in the kidney is expressed in nephron tubules. In humans and animal models with chronic kidney disease, renal GCGR expression is reduced. However, the role of kidney GCGR in normal renal function and in disease development has not been addressed. Here, we examined its role by analyzing mice with constitutive or conditional kidney-specific loss of the Gcgr. Adult renal Gcgr knockout mice exhibit metabolic dysregulation and a functional impairment of the kidneys. These mice exhibit hyperaminoacidemia associated with reduced kidney glucose output, oxidative stress, enhanced inflammasome activity, and excess lipid accumulation in the kidney...

Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed in cell types beyond adipocytes, particularly in kidney tubular cells, but its local renal role is unknown. We assessed the impact of renal adiponectin by utilizing male inducible kidney tubular cell-specific adiponectin overexpression or knockout mice. Kidney-specific adiponectin overexpression induces a doubling of phosphoenolpyruvate carboxylase expression and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates and an upregulation of fatty acid oxidation (FAO)...

Vagal afferent neuronal somas are in the nodose and jugular ganglia. In this study, we identified extraganglionic neurons in whole-mount preparations of the vagus nerves from Phox2b-Cre-ZsGreen transgenic mice. These neurons are typically arranged in small clusters and monolayers along the cervical vagus nerve. Although infrequent, these neurons were sometimes observed along the thoracic and esophageal vagus. We performed RNAscope in situ hybridization and confirmed that the extraganglionic neurons detected in this transgenic mouse strain expressed vagal afferent markers (i...

Immunohistochemistry is a commonly used technique in research and pathology laboratories worldwide. However, in recent years, there has been a significant decrease in the number of Pubmed entries using the term immunohistochemistry. This decline can be attributed to two factors: increased awareness of the issue of unreliable research antibodies and the availability of novel RNA in situ hybridization techniques. Using the example of immunohistochemistry, this text discusses the factors that can affect good laboratory and publishing practices, or their lack thereof...

Microglia play a role in the pathogenesis of many retinal diseases. Fundus spots in mice often correlate with the accumulation of activated subretinal microglia. Here we use a semiquantitative fundus spot scoring scale in combination with an unbiased, state-of-the-science forward genetics pipeline to identify causative associations between chemically induced mutations and fundus spot phenotypes. Among several associations, we focus on a missense mutation in Lipe linked to an increase in yellow fundus spots in C57BL/6J mice...

Animals that consume fermenting fruit and nectar are at risk of exposure to ethanol and the detrimental effects of inebriation. In this report, we show that the hormone FGF21, which is strongly induced by ethanol in murine and human liver, stimulates arousal from intoxication without changing ethanol catabolism. Mice lacking FGF21 take longer than wild-type littermates to recover their righting reflex and balance following ethanol exposure. Conversely, pharmacologic FGF21 administration reduces the time needed for mice to recover from ethanol-induced unconsciousness and ataxia...

This article reflects on the disastrous effects that the managerial model had on contemporary biomedical research. It is argued that the time has come to reinvent an "antibureaucratic laboratory" which favors decision-making based on the intrinsic values of the researcher rather than the need to please external committees. Towards achieving this goal, governmental agencies should rely less on peer review and adopt new funding mechanisms. It is also predicted that the advent of the antibureaucratic laboratory" will only come at the cost of a revolution in the mentalities of all those involved in research...

Ghrelin is a stomach-derived peptide hormone that acts via the growth hormone secretagogue receptor (GHSR) and displays a plethora of neuroendocrine, metabolic, autonomic and behavioral actions. It has been proposed that some actions of ghrelin are exerted via the vagus nerve, which provides a bidirectional communication between the central nervous system and peripheral systems. The vagus nerve comprises sensory fibers, which originate from neurons of the nodose and jugular ganglia, and motor fibers, which originate from neurons of the medulla...

Trypanozoon infections in equids are caused by three parasite species in the Trypanozoon subgenus: Trypanosoma equiperdum, T. brucei and T. evansi. They are respectively responsible for infectious diseases dourine, nagana and surra. Due to the threat that Trypanozoon infection represents for international horse trading, accurate diagnostic tests are crucial. Current tests suffer from poor sensitivity and specificity, due in the first case to the transient presence of parasites in the blood and in the second, to antigenic cross-reactivity among Trypanozoon subspecies...

OBJECTIVE: The vagus nerve provides a direct line of communication between the gut and the brain for proper regulation of energy balance and glucose homeostasis. Short-chain fatty acids (SCFAs) produced via gut microbiota fermentation of dietary fiber have been proposed to regulate host metabolism and feeding behavior via the vagus nerve, but the molecular mechanisms have not yet been elucidated. We sought to identify the G-protein-coupled receptors within vagal neurons that mediate the physiological and therapeutic benefits of SCFAs...

This study describes a protocol for the multiplex in situ hybridization (ISH) of the mouse jugular-nodose ganglia, with a particular emphasis on detecting the expression of G protein-coupled receptors (GPCRs). Formalin-fixed jugular-nodose ganglia were processed with the RNAscope technology to simultaneously detect the expression of two representative GPCRs (cholecystokinin and ghrelin receptors) in combination with one marker gene of either nodose (paired-like homeobox 2b, Phox2b) or jugular afferent neurons (PR domain zinc finger protein 12, Prdm12)...

Iron overload is positively associated with diabetes risk. However, the role of iron in adipose tissue remains incompletely understood. Here, we report that transferrin-receptor-1-mediated iron uptake is differentially required for distinct subtypes of adipocytes. Notably, adipocyte-specific transferrin receptor 1 deficiency substantially protects mice from high-fat-diet-induced metabolic disorders. Mechanistically, low cellular iron levels have a positive impact on the health of the white adipose tissue and can restrict lipid absorption from the intestine through modulation of vesicular transport in enterocytes following high-fat diet feeding...

Designing and synthesising new metastable compounds is a major challenge of today's material science. While exploration of metastable oxides has seen decades-long advancement thanks to the topochemical deintercalation of oxygen as recently spotlighted with the discovery of nickelate superconductor, such unique synthetic pathway has not yet been found for chalcogenide compounds. Here we combine an original soft chemistry approach, structure prediction calculations and advanced electron microscopy techniques to demonstrate the topochemical deintercalation/reintercalation of sulfur in a layered oxychalcogenide leading to the design of novel metastable phases...

The excitation of vagal mechanoreceptors located in the stomach wall directly contributes to satiation. Thus, a loss of gastric innervation would normally be expected to result in abrogated satiation, hyperphagia, and unwanted weight gain. While Roux-en-Y-gastric bypass (RYGB) inevitably results in gastric denervation, paradoxically, bypassed subjects continue to experience satiation. Inspired by the literature in neurology on phantom limbs, I propose a new hypothesis in which damage to the stomach innervation during RYGB, including its vagal supply, leads to large-scale maladaptive changes in viscerosensory nerves and connected brain circuits...

In 1883, a case of daring plagiarism was revealed during a session of the Biology Society in Paris. This article discusses the details of this plagiarism and the identity of its perpetrator, a physician by the name of Spiridion Kanellis.

There has been a long-standing debate regarding the role of peripheral afferents in mediating rapid-onset anorexia among other responses elicited by peripheral inflammatory insults. Thus, the current study assessed the sufficiency of peripheral afferents expressing toll-like receptor 4 (TLR4) to the initiation of the anorexia caused by peripheral bacterial lipopolysaccharide (LPS). We generated a Tlr4 null (Tlr4LoxTB ) mouse in which Tlr4 expression is globally disrupted by a loxP-flanked transcription blocking cassette...

The mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging...

The mouse accessory olfactory system (AOS) supports social and reproductive behavior through the sensation of environmental chemosignals. A growing number of excreted steroids have been shown to be potent AOS cues, including bile acids (BAs) found in feces. As is still the case with most AOS ligands, the specific receptors used by vomeronasal sensory neurons (VSNs) to detect BAs remain unknown. To identify VSN BA receptors, we first performed a deep analysis of VSN BA tuning using volumetric GCaMP6f/s Ca2+ imaging...