Biology subjects

Bedenbaugh, M. N.

Publications and source records attributed to Bedenbaugh, M. N..

4 recordsLinked to original sources

bioRxiv2026

Sex-specific control of feeding and defensive behaviors by MC3R neurons in the bed nuclei of the stria terminalis

The bed nuclei of the stria terminalis (BST) is a nuclear complex that coordinates neuroendocrine, autonomic, and behavioral responses associated with maintaining homeostasis. Here, we demonstrate that melanocortin 3 receptor (MC3R) neurons in the BST (BSTMC3R) play a key role in modulating feeding behaviors and responses to stressful events. BSTMC3R neurons are primarily GABAergic and colocalize with neuropeptides known to regulate feeding and affective behaviors. Chemogenetic activation of BSTMC3R neurons causes reduced feeding, particularly in males. BSTMC3R neurons are also robustly activated by stress and can control responses to stress and defensive behaviors in both sexes. Whole-brain monosynaptic rabies tracing identified multiple sexually dimorphic inputs to BSTMC3R neurons that may contribute to observed functional sexual dimorphisms. Altogether, these data reveal that BSTMC3R neurons participate in sexually dimorphic circuits that influence feeding and defensive behaviors, responses to stress, and may represent a potential therapeutic target for stress- and eating-related disorders.

neuroscience↗

bioRxiv2024

Endothelial β1 Integrins are Necessary for Microvascular Function and Glucose Uptake

Microvascular insulin delivery to myocytes is rate limiting for the onset of insulin-stimulated muscle glucose uptake. The structural integrity of capillaries of the microvasculature is regulated, in part, by a family of transmembrane adhesion receptors known as integrins, which are composed of an and {beta} subunit. The integrin {beta}1 (itg{beta}1) subunit is highly expressed in endothelial cells (EC). EC itg{beta}1 is necessary for the formation of capillary networks during embryonic during development and its knockdown in adult mice blunts the reactive hyperemia that manifests during ischemia reperfusion. In this study we investigated the contribution of skeletal muscle EC itg{beta}1 in microcirculatory function and glucose uptake. We hypothesized that loss of EC itg{beta}1 would impair microvascular hemodynamics and glucose uptake during insulin stimulation, creating delivery-mediated insulin resistance. An itg{beta}1 knockdown mouse model was developed to avoid lethality of embryonic gene knockout and the deteriorating health resulting from early post-natal inducible gene deletion. We found that mice with (itg{beta}1fl/flSCLcre) and without (itg{beta}1fl/fl) inducible stem cell leukemia cre recombinase (SLCcre) expression at 10 days post cre induction have comparable exercise tolerance and pulmonary and cardiac functions. We quantified microcirculatory hemodynamics using intravital microscopy and the ability of mice to respond to the high metabolic demands of insulin-stimulated muscle using a hyperinsulinemic-euglycemia clamp. We show that itg{beta}1fl/flSCLcre mice compared to itg{beta}1fl/fl littermates have, i) deficits in capillary flow rate, flow heterogeneity, and capillary density; ii) impaired insulin-stimulated glucose uptake despite sufficient transcapillary insulin efflux; and iii) reduced insulin-stimulated glucose uptake due to perfusion-limited glucose delivery. Thus, EC itg{beta}1 is necessary for microcirculatory function and to meet the metabolic challenge of insulin stimulation.

physiology↗

bioRxiv2024

Microglia are Required for Developmental Specification of AgRP Innervation in the Hypothalamus of Offspring Exposed to Maternal High Fat Diet During Lactation

Agouti-related peptide (AgRP) neurons in the arcuate nucleus of the hypothalamus respond to multiple metabolic signals and distribute neuroendocrine information to other brain regions such as the paraventricular hypothalamic nucleus (PVH), which plays a central role in metabolic homeostasis. Neural projections from AgRP neurons to the PVH form during the postnatal lactational period in mice and these projections are reduced in offspring of dams that consumed a high-fat diet (HFD) during lactation (MHFD-L). Here we used immunohistochemistry to visualize microglial morphology in MHFD-L offspring and identified changes that were regionally localized to the PVH and appeared temporally restricted to the period when AgRP neurons innervate this region. In addition, axon labeling experiments revealed that microglia engulf AgRP terminals in the PVH, and that the density of AgRP innervation to the PVH in MHFD-L offspring may be dependent on microglia, because microglial depletion blocked the decrease in PVH AgRP innervation observed in MHFD-L offspring, as well as prevented the increased body weight exhibited at weaning. Together, these findings suggest that microglia are activated by exposure to MHFD-L and interact directly with AgRP axons during postnatal development to permanently alter innervation of the PVH, with implications for developmental programming of metabolic phenotype. Impact StatementMicroglia appear to play an essential role in specifying patterns of hypothalamic innervation during development in response to maternal HFD exposure, which may contribute to developmental programming of metabolic phenotype.

neuroscience↗

bioRxiv2024

BNST GluN2D-containing NMDARs contribute to ethanol intake but not negative affective behaviors in female mice

Alcohol use disorder (AUD) is a chronic, relapsing disease, highly comorbid with anxiety and depression. The bed nucleus of the stria terminalis (BNST), and Crh+ neurons in this region are thought to play a key role in chronic ethanol-induced increases in volitional ethanol intake. This role has been hypothesized to be driven by emergent BNST-dependent negative affective behaviors. Indeed, we report here that in female mice undergoing a home cage chronic drinking forced abstinence model (CDFA), excitatory transmission undergoes time-dependent upregulation in BNST Crh+ cells. Excitatory NMDA receptors (NMDARs) are a major target of ethanol, and chronic ethanol exposure has been shown to regulate NMDAR function and expression. GluN2D subunit-containing NMDARs have emerged as a target of interest due to their limited distribution and potential roles in affective behavior. We find that knockdown of dorsal BNST (dBNST) GluN2D expression significantly decreases ethanol intake in female, but not male, mice. While BNST Grin2b expression was significantly increased in protracted abstinence following CDFA, no differences in Grin2d expression were observed in dBNST or specifically in dBNST Crh+ neurons. Finally, to determine the impact of GluN2D expression on negative affective behaviors, open field, elevated zero maze, and forced swim tasks were used to measure anxiety- and depressive-like behaviors in constitutive and conditional BNST GluN2D knockout mice. Surprisingly, we find that deletion of GluN2D fails to alter negative affect in ethanol-naive female mice. Together, these data suggest a role for BNST GluN2D-containing NMDARs in ethanol drinking behaviors but not abstinence from ethanol, highlighting potential sex differences and behavioral specificity in the context of AUD behaviors. Overall, these data further suggest roles for BNST synaptic signaling in volitional ethanol intake that are partially independent of actions on affective behavior.

neuroscience↗