Diacylglycerol lipase alpha in astrocytes is involved in maternal care and affective behaviors. Issue 2 (2nd September 2020)

• Record Type: Journal Article
• Authors: Schuele, Lena‐Louise; Glasmacher, Sandra; Gertsch, Jürg; Roggan, Marie Denise; Transfeld, Janis‐Lisa; Bindila, Laura; Lutz, Beat; Kolbe, Carl‐Christian; Bilkei‐Gorzo, Andras; Zimmer, Andreas; Leidmaa, Este
• Is Part Of: Glia. Volume 69:Issue 2(2021)
• Page Start: 377
• Page End: 391
• Publication Date: 2020-09-02
• Subjects: 2‐arachidonoylglycerol -- astrocyte‐specific knockout -- depression -- maternal behavior -- targeted lipidomics -- tripartite synapse; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23903
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Genetic deletion of cannabinoid CB1 receptors or diacylglycerol lipase alpha (DAGLa), the main enzyme involved in the synthesis of the endocannabinoid (eCB) 2‐arachidonoylglycerol (2‐AG), produced profound phenotypes in animal models of depression‐related behaviors. Furthermore, clinical studies have shown that antagonists of CB1 can increase the incidence and severity of major depressive episodes. However, the underlying pathomechanisms are largely unknown. In this study, we have focused on the possible involvement of astrocytes. Using the highly sensitive RNAscope technology, we show for the first time that a subpopulation of astrocytes in the adult mouse brain expresses Dagla, albeit at low levels. Targeted lipidomics revealed that astrocytic DAGLa only accounts for a minor percentage of the steady‐state brain 2‐AG levels and other arachidonic acid derived lipids like prostaglandins. Nevertheless, the deletion of Dagla in adult mouse astrocytes had profound behavioral consequences with significantly increased depressive‐like behavioral responses and striking effects on maternal behavior, corresponding with increased levels of serum progesterone and estradiol. Our findings therefore indicate that lipids from the DAGLa metabolic axis in astrocytes play a key regulatory role in affective behaviors. Main points: DAGLa is expressed in a subpopulation of astrocytes, albeit at low levels. Astrocytic DAGLa only accounts for a small percentage of overall brain 2‐AG levels. Astrocytic knockout of Dagla leads to depression‐like behavior and maternal care deficits.