P2.29. THE ROLE OF LIPID METABOLISM AND CIRCULATING MIRNAS IN THE INTERGENERATIONAL TRANSMISSION OF THE EFFECTS OF PARENTAL ADVERSE CHILDHOOD EXPERIENCES
Magdalena Gomółka1, Weronika Tomaszewska1, Sandra Binias2, Regina Nadalinska1, Ali Jawaid1
1 Translational Neuropsychiatry Research Group (TREND Lab) Life Sciences & Biotechnology Center Łukasiewicz Research Network PORT – Polish Centre of Technology Development, Wrocław, Poland
2 Laboratory of Sequencing, Nencki Institute of Experimental Biology PAS, Warsaw, Poland
INTRODUCTION: Childhood trauma is an important risk factor for psychiatric and physical ailments during adulthood. Emerging evidence suggests that some of its behavioral and metabolic symptoms are transmissible across generations. Intergenerational transmission of the effects of trauma is postulated to involve changes in germline non-coding RNAs. However, it is unclear how childhood trauma affects ncRNAs in the gametes. Circulating ncRNAs, such as miRNAs, majorly carried by lipid-associated factors in the body fluids, appear as important candidates for carrying the trauma effects to the gametes for intergenerational transmission.
AIM(S): Synergizing investigation in a mouse model of ACE induced via unpredictable maternal separation and unpredictable maternal stress (MSUS) and cross-injections, we hypothesize that lipid-associated miRNAs communicate the effects of ACE to the germline for intergenerational transmission.
METHOD(S): Intergenerational behavioral and metabolic phenotyping was performed, supplemented with small RNA sequencing followed by qPCR. Cross-injections of lipid-associated carriers into the tail vein of mice performed.
RESULTS: Offspring of both MSUS- and HFD-exposed male mice showed impaired glucose tolerance, depressive-like behavior and anxiety. Cross-injections from MSUS into CTRL mice prolonged the offspring latency to enter open arms in Elevated Plus Maze test. Cross-injections from MSUS into CTRL mice recapitulated the offspring metabolic phenotype associated with MSUS in Glucose tolerance test. Cross-injections from VE mice into MSUS mice partially mitigated the metabolic MSUS phenotype.
CONCLUSIONS: Injections of MSUS-material is sufficient and necessary to induce the intergenerational metabolic phenotype associated with MSUS while lipid-modifying interventions can potentially alter the intergenerational metabolic MSUS phenotype. This research provides proof-of-concept for a role of lipids and circulating miRNAs in communicating the effects of ACE to the germline for intergenerational sequelae.
FINANCIAL SUPPORT: LIPITRATE: National Science Centre (NCN) Poland (SONATA; DEC-2020/39/D/NZ3/01887)