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

Area of Science:

• Neuroscience
• Endocrinology
• Behavioral Science

Background:

• Orexin (OX) neurons in the lateral hypothalamic area (LHA) are linked to obesity and mood disorders.
• These OX neurons co-express various proteins, including delta-like homolog 1 (DLK1), which may play a role in physiological regulation.

Purpose of the Study:

• To investigate the role of DLK1, co-expressed in OX neurons, in regulating energy balance and anxio-depressive behaviors.
• To determine if DLK1 contributes to the physiological functions of OX neurons.

Main Methods:

• Investigated DLK1 co-expression with OX neurons across species (rats, mice, humans).
• Utilized a viral lesion strategy to selectively delete DLK1 in the LHA of adult mice (DLK1^Null).
• Assessed body weight, ingestive behavior, locomotor activity, anxiety, and depression in DLK1^Null mice.

Main Results:

• DLK1 co-expression with OX neurons varies across species; mice models are relevant for human physiology.
• Adult-onset DLK1 deletion in the LHA did not alter body weight or ingestive behavior.
• DLK1^Null mice exhibited increased locomotor activity and reduced anxiety and depression behaviors.

Conclusions:

• DLK1 expressed by OX neurons in the LHA significantly influences anxio-depressive behaviors.
• DLK1's primary role appears to be in behavioral regulation, not energy balance.
• These findings highlight DLK1 as a potential target for mood disorder therapies.