DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance

Brain Sciences

Rebecca Pratt¹  Elahé Crockett²  Gina Leinninger³  Jaylyn Kelly³  Raluca Bugescu³  Morgan Sotzen³  Anna Makela³  Tatiyana Harris³  Graham Atkin⁴  Cheryl Sisk⁵ 

[1] Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA;Department of Medicine, Michigan State University, East Lansing, MI 48824, USA;Department of Physiology, Michigan State University, East Lansing, MI 48824, USA;Department of Radiology, Michigan State University, East Lansing, MI 48824, USA;Neuroscience Program, Department of Psychology, Michigan State University, East Lansing, MI 48824, USA;

关键词: lateral hypothalamic area;    orexin/hypocretin;    delta-like-1 homolog (DLK1);    feeding;    body weight;    anxiety;   

DOI  :  10.3390/brainsci10120975

来源: DOAJ

【 摘 要 】

Lateral hypothalamic area (LHA) neurons expressing the neuropeptide orexin (OX) are implicated in obesity and anxio-depression. However, these neurons release OX as well as a host of other proteins that might contribute to normal physiology and disease states. We hypothesized that delta-like homolog 1 (DLK1), a protein reported to be co-expressed by all OX neurons, contributes to the regulation of energy balance and/or anxio-depression. Consistent with previous reports, we found that all rat OX neurons co-express DLK1. Yet, in mice and humans only a subset of OX neurons co-expressed DLK1. Since human OX-DLK1 distribution is more similar to mice than rats, mice are a comparable model to assess the human physiologic role of DLK1. We therefore used a viral lesion strategy to selectively delete DLK1 within the LHA of adult mice (DLK1^Null) to reveal its role in body weight and behavior. Adult-onset DLK1 deletion had no impact on body weight or ingestive behavior. However, DLK1^Null mice engaged in more locomotor activity than control mice and had decreased anxiety and depression measured via the elevated plus maze and forced swim tests. These data suggest that DLK1 expression via DLK1-expressing OX neurons primarily contributes to anxio-depression behaviors without impacting body weight.

【 授权许可】

Unknown