Journal Article

SRF depletion in early life contributes to social interaction deficits in the adulthood

Pekala, Martyna, Michaluk, Piotr, Krysiak, Anna, Nader, Karolina, Jaworski, Jacek, Roszkowska, Matylda, Kondrakiewicz, Ludwika, Puścian, Alicja, Majchrowicz, Lena, Knapska, Ewelina, Kalita, Katarzyna, Kaczmarek, Leszek, Beroun, Anna

2022

Overview

Alterations in social behavior are core symptoms of major developmental neuropsychiatric diseases such as autism spectrum disorders or schizophrenia. Hence, understanding their molecular and cellular underpinnings constitutes the major research task. Dysregulation of the global gene expression program in the developing brain leads to modifications in a number of neuronal connections, synaptic strength and shape, causing unbalanced neuronal plasticity, which may be important substrate in the pathogenesis of neurodevelopmental disorders, contributing to their clinical outcome. Serum response factor (SRF) is a major transcription factor in the brain. The behavioral influence of SRF deletion during neuronal differentiation and maturation has never been studied because previous attempts to knock-out the gene caused premature death. Herein, we generated mice that lacked SRF from early postnatal development to precisely investigate the role of SRF starting in the specific time window before maturation of excitatory synapses that are located on dendritic spine occurs. We show that the time-controlled loss of SRF in neurons alters specific aspects of social behaviors in SRF knock-out mice, and causes deficits in developmental spine maturation at both the structural and functional levels, including downregulated expression of the AMPARs subunits GluA1 and GluA2, and increases the percentage of filopodial/immature dendritic spines. In aggregate, our study uncovers the consequences of postnatal SRF elimination for spine maturation and social interactions revealing novel mechanisms underlying developmental neuropsychiatric diseases.

• Publisher: Springer International Publishing,Springer Nature B.V
• Subject: adulthood / Animals / Autism / Biochemistry / Biomedical and Life Sciences / Biomedicine / blood serum / Brain / Cell Biology / death / dendrites / Dendritic spines / Dendritic Spines - physiology / Depletion / Disorders / Gene expression / genes / Life Sciences / Maturation / Mental disorders / Mice / Neurodevelopmental disorders / Neuronal Plasticity / Neuroplasticity / Original / Original Article / Pathogenesis / postnatal development / Schizophrenia / Serum response factor / Serum Response Factor - genetics / Serum Response Factor - metabolism / Signs and symptoms / Social behavior / Social factors / Social Interaction / Social interactions / Spine / Structure-function relationships / Substrates / Synapses / Synapses - metabolism / Synaptic plasticity / Synaptic strength / transcription factors / Windows (intervals)