A1 Refereed original research article in a scientific journal
The supramammillary nucleus controls anxiety-like behavior; key role of GLP-1R
Authors: Lopez-Ferreras L, Eerola K, Shevchouk OT, Richard JE, Nilsson FH, Jansson LE, Hayes MR, Skibicka KP
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Publication year: 2020
Journal: Psychoneuroendocrinology
Journal name in source: PSYCHONEUROENDOCRINOLOGY
Journal acronym: PSYCHONEUROENDOCRINO
Article number: ARTN 104720
Volume: 119
Number of pages: 12
ISSN: 0306-4530
DOI: https://doi.org/10.1016/j.psyneuen.2020.104720
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/48913801
Anxiety disorders are among the most prevalent categories of mental illnesses. The gut-brain axis, along with gastrointestinally-derived neuropeptides, like glucagon-like peptide-1 (GLP-1), are emerging as potential key regulators of emotionality, including anxiety behavior. However, the neuroanatomical substrates from which GLP-1 exerts its anxiogenic effect remain poorly characterized. Here we focus on a relatively new candidate nucleus, the supramammillary nucleus (SuM), located just caudal to the lateral hypothalamus and ventral to the ventral tegmental area. Our focus on the SuM is supported by previous data showing expression of GLP-1R mRNA throughout the SuM and activation of the SuM during anxiety-inducing behaviors in rodents. Data show that chemogenetic activation of neurons in the SuM results in an anxiolytic response in male and female rats. In contrast, selective activation of SuM GLP-1R, by microinjection of a GLP-1R agonist exendin-4 into the SuM resulted in potent anxiety-like behavior, measured in both open field and elevated plus maze tests in male and female rats. This anxiogenic effect of GLP-1R activation persisted after high-fat diet exposure. Importantly, reduction of GLP-1R expression in the SuM, by AAV-shRNA GLP-1R knockdown, resulted in a clear anxiolytic response; an effect only observed in female rats. Our data identify a new neural substrate for GLP-1 control of anxiety-like behavior and indicate that the SuM GLP-1R are sufficient for anxiogenesis in both sexes, but necessary only in females.
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