Hypothalamic GABAergic Neurons Expressing Cellular Retinoic Acid Binding Protein 1 (CRABP1) Are Sensitive to Metabolic Status and Liraglutide in Male Mice.

INTRODUCTION: Owing to their privileged anatomical location, neurons of the arcuate nucleus of the hypothalamus (ARC) play critical roles in sensing and responding to metabolic signals such as leptin and glucagon-like peptide 1 (GLP-1). In addition to the well-known proopiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neurons, subpopulations of GABAergic neurons are emerging as key regulators of energy balance. However, the precise identity of these metabolic neurons is still elusive. Here, we identified and characterized the molecular signature of a novel population of GABAergic neurons of the ARC expressing Cellular retinoic acid binding protein 1 (Crabp1). METHODS: Using a combination of immunohistochemistry and in situ hybridization techniques, we investigated the expression of Crabp1 across the mouse brain and characterized the molecular identity of Crabp1ARC neurons. We also determined whether Crabp1ARC neurons are sensitive to fasting, leptin, and GLP1R agonism by assessing cFOS immunoreactivity as a marker of neuronal activity. RESULTS: Crabp1ARC neurons represent a novel GABAergic neuronal population robustly enriched in the ARC and are distinct from the prototypical melanocortin neurons. Crabp1ARC neurons overlap with three subpopulations of yet uncharacterized ARC neurons expressing Htr3b, Tbx19, and Tmem215. Notably, Crabp1ARC neurons express receptors for metabolic hormones and their activity is modulated by the nutritional state and GLP1R agonism. CONCLUSION: Crabp1ARC neurons represent a novel heterogeneous population of GABAergic neurons sensitive to metabolic status.

Environmental conditions of recognition memory testing induce neurovascular changes in the hippocampus in a sex-specific manner in mice.

Experiences are linked to emotions impacting memory consolidation and associated brain neuronal circuits. Posttraumatic stress disorder is an example of strong negative emotions affecting memory processes by flashbacks of past traumas. Stress-related memory deficits are also observed in major depressive disorder (MDD). We recently highlighted that sex-specific blood-brain barrier (BBB) alterations underlie stress responses in mice and human depression. However, little is known about the relationship between emotional valence, memory encoding and BBB gene expression. Here, we investigated the effects of novel object recognition (NOR) test, an experience considered of neutral emotional valence, on BBB properties in dorsal vs ventral hippocampus (HIPP) in the context of various environmental conditions (arena size, handling, age). The HIPP is a brain area central for learning and memory processes with the dorsal and ventral subregions being associated with working memory vs reference memory retrieval, respectively. Expression of genes related to BBB integrity are altered in line with learning and memory processes in a region- and sex-specific manner. We observed correlations between poor learning, anxiety, stress-induced corticosterone release and changes in BBB-associated gene expression. Comparison of BBB transcriptomes between sexes also revealed profound differences at baseline in both ventral and dorsal HIPP. Finally, we identified circulating vascular biomarkers, such as sE-selectin and matrix metallopeptidase 9 (MMP-9), altered following NOR exposure supporting that recognition memory formation has an impact on the neurovasculature. Although deemed as a neutral valence test, NOR experimental conditions can shift it toward a negative valence, impacting performance and highlighting the need to minimize anxiety when performing this commonly used test in mice.

Strategies to engage family physicians in primary care research: A systematic review.

RATIONALE: Moving towards high quality primary health care, involving family physicians in primary care research becomes an essential prerequisite to ensures a better adoption and routinization of patient-centred, evidence-based practices. AIM: To assess the effectiveness of strategies to engage family physicians in primary care research. METHODS: We systematically reviewed evidence for strategies used to engage family physicians in primary care research. We included any study design that reported at least one quantitative outcome. Searches were carried out on MEDLINE, Embase, PsycINFO and Web of Science. Pairs of reviewers independently screened for publications in two stages using standardized forms. We performed data analysis through a narrative synthesis approach, using the Reasoned-action approach as framework. RESULTS: A total of 4859 deduped records were identified of which 41 studies met the eligibility criteria and were included for analysis. The majority of studies (n = 35) investigated family physician's participation in a research project. They aimed to influence family physicians' intention (n = 7) or their ability (n = 3) to participate in a research project. Three types of strategies (compensation/incentive, recruitment by a peer and support from a research network or an academic institution) demonstrated a significant increase in participation rate. Methodological quality of the studies evaluating these strategies was relatively low. Few studies (n = 6) targeted research capacity-building programmes with no significant impact noted. CONCLUSION: Numerous strategies have been used to engage family physicians in primary care research, but few studies evaluated their effectiveness in a rigorous way. REGISTRATION: The protocol of this review was registered with the SPOR Evidence Alliance and on the PROSPERO platform (registration number: CRD42020189322).