Circular RNAs (circRNAs) are extraordinarily enriched in the brain, the majority of them are generated from neuronal specific genes. Their expression is regulated by neuronal activity and they might feed-back modulating neuronal plasticity. Growing experimental evidence suggests their implication in the etiology of several human developmental and neurological diseases. Recently, we identified the differential expression profile of circRNAs in the BTBR T + tf/J (BTBR) mouse model for Autism Spectrum Disorder (ASD) Gasparini et al., 2020). BTBR mice are a valuable model for idiopathic autism, that recapitulates several human core symptoms. As ASD has recently defined a "synaptic" disease, in which key effectors of synaptic signaling are dysregulated, we hypothesized that the identified ASD-related circRNAs might be implicated in neuronal signaling. To verify this hypothesis, in the present study selected ASD-related circRNAs were further characterized during development, neuronal differentiation and synaptic plasticity. Ex vivo expression pattern of circCdh9 and circRmst was compared in different brain regions of BTBR and control mice. Levels of selected circRNAs were characterized ex vivo during prenatal and postnatal development, and in primary neuronal cultures at different stages of differentiation in control mice. Finally, expression changes of circRNAs were assessed in a neuronal paradigm of homeostatic plasticity. Experiments are in progress to define the molecular function of selected ASD-related circRNAs
Characterization of circular RNAs dysregulated in autism spectrum disorder
Cecilia Mannironi
2020
Abstract
Circular RNAs (circRNAs) are extraordinarily enriched in the brain, the majority of them are generated from neuronal specific genes. Their expression is regulated by neuronal activity and they might feed-back modulating neuronal plasticity. Growing experimental evidence suggests their implication in the etiology of several human developmental and neurological diseases. Recently, we identified the differential expression profile of circRNAs in the BTBR T + tf/J (BTBR) mouse model for Autism Spectrum Disorder (ASD) Gasparini et al., 2020). BTBR mice are a valuable model for idiopathic autism, that recapitulates several human core symptoms. As ASD has recently defined a "synaptic" disease, in which key effectors of synaptic signaling are dysregulated, we hypothesized that the identified ASD-related circRNAs might be implicated in neuronal signaling. To verify this hypothesis, in the present study selected ASD-related circRNAs were further characterized during development, neuronal differentiation and synaptic plasticity. Ex vivo expression pattern of circCdh9 and circRmst was compared in different brain regions of BTBR and control mice. Levels of selected circRNAs were characterized ex vivo during prenatal and postnatal development, and in primary neuronal cultures at different stages of differentiation in control mice. Finally, expression changes of circRNAs were assessed in a neuronal paradigm of homeostatic plasticity. Experiments are in progress to define the molecular function of selected ASD-related circRNAsI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.