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

Harris, Tatiyana; Bugescu, Raluca; Kelly, Jaylyn; Makela, Anna; Sotzen, Morgan; Sisk, Cheryl; Atkin, Graham; Pratt, Rebecca; Crockett, Elahé; Leinninger, Gina

doi:10.3390/brainsci10120975

Open AccessArticle

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

by

Tatiyana Harris

¹,

Raluca Bugescu

¹,

Jaylyn Kelly

¹,

Anna Makela

¹,

Morgan Sotzen

¹,

Cheryl Sisk

²,

Graham Atkin

³,

Rebecca Pratt

⁴

,

Elahé Crockett

⁵ and

Gina Leinninger

^1,*

¹

Department of Physiology, Michigan State University, East Lansing, MI 48824, USA

²

Neuroscience Program, Department of Psychology, Michigan State University, East Lansing, MI 48824, USA

³

Department of Radiology, Michigan State University, East Lansing, MI 48824, USA

⁴

Department of Foundational Medical Studies, Oakland University William Beaumont School of Medicine, Rochester, MI 48309, USA

⁵

Department of Medicine, Michigan State University, East Lansing, MI 48824, USA

^*

Author to whom correspondence should be addressed.

Brain Sci. 2020, 10(12), 975; https://doi.org/10.3390/brainsci10120975

Submission received: 17 November 2020 / Revised: 8 December 2020 / Accepted: 9 December 2020 / Published: 12 December 2020

(This article belongs to the Special Issue Neuropeptides and Psychiatric Disorders)

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Abstract

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.

Keywords: lateral hypothalamic area; orexin/hypocretin; delta-like-1 homolog (DLK1); feeding; body weight; anxiety; depression; locomotor activity

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MDPI and ACS Style

Harris, T.; Bugescu, R.; Kelly, J.; Makela, A.; Sotzen, M.; Sisk, C.; Atkin, G.; Pratt, R.; Crockett, E.; Leinninger, G. DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance. Brain Sci. 2020, 10, 975. https://doi.org/10.3390/brainsci10120975

AMA Style

Harris T, Bugescu R, Kelly J, Makela A, Sotzen M, Sisk C, Atkin G, Pratt R, Crockett E, Leinninger G. DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance. Brain Sciences. 2020; 10(12):975. https://doi.org/10.3390/brainsci10120975

Chicago/Turabian Style

Harris, Tatiyana, Raluca Bugescu, Jaylyn Kelly, Anna Makela, Morgan Sotzen, Cheryl Sisk, Graham Atkin, Rebecca Pratt, Elahé Crockett, and Gina Leinninger. 2020. "DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance" Brain Sciences 10, no. 12: 975. https://doi.org/10.3390/brainsci10120975

APA Style

Harris, T., Bugescu, R., Kelly, J., Makela, A., Sotzen, M., Sisk, C., Atkin, G., Pratt, R., Crockett, E., & Leinninger, G. (2020). DLK1 Expressed in Mouse Orexin Neurons Modulates Anxio-Depressive Behavior but Not Energy Balance. Brain Sciences, 10(12), 975. https://doi.org/10.3390/brainsci10120975

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

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