Maternal separation with early weaning impairs neuron-glia integrity: non-invasive evaluation and substructure demonstration

Haiyan Zeng,Haiyun Xu,Zhijia Yu,Zhiwei Shen,Qingjun Huang,Shuqin Xu,Zhuozhi Dai,Wenqiang Wang,Xi Chen,Xiaolei Zhang,Renhua Wu,Gen Yan

doi:10.1038/s41598-020-76640-y

Abstract

Astrocytes and oligodendrocytes play essential roles in regulating neural signal transduction along neural circuits in CNS. The perfect coordination of neuron/astrocyte and neuron/oligodendrocyte entities was termed as neuron-glia integrity recently. Here we monitored the status of neuron-glia integrity via non-invasive neuroimaging methods and demonstrated the substructures of it using other approaches in an animal model of maternal separation with early weaning (MSEW), which mimics early life neglect and abuse in humans. Compared to controls, MSEW rats showed higher glutamate level, but lower GABA in prefrontal cortex (PFC) detected by chemical exchange saturation transfer and 1H-MRS methods, lower levels of glial glutamate transporter-1 and ATP-α, but increased levels of glutamate decarboxylase-65 and glutamine synthetase in PFC; reduced fractional anisotropy in various brain regions revealed by diffusion tensor imaging, along with increased levels of N-acetyl-aspartate measured by 1H-MRS; and hypomyelination in PFC as evidenced by relevant cellular and molecular changes.

Highlights

Astrocytes and oligodendrocytes play essential roles in regulating neural signal transduction along neural circuits in central nervous system (CNS)
For the first time we measured the integrity of neuron-glia entities in brains of living rats by non-invasive neuroimaging techniques of 1H-MRS, chemical exchange saturation transfer (CEST) of glutamate (GluCEST), and diffusion tensor imaging (DTI). 1H-MRS has been extensively used in clinical practice and psychiatric research[11], but no prior studies applied it to evaluate the neuron-glia entities
On postnatal day 60 (PD 60), rats in the maternal separation with early weaning (MSEW) and Control groups were subjected to open field test to measure their locomotor activity, exploratory behavior, and anxiety level

Summary

Introduction

Astrocytes and oligodendrocytes play essential roles in regulating neural signal transduction along neural circuits in CNS. N-acetyl-aspartate (NAA) is considered the neurochemical correlate of axon-myelin entity because it involves in myelination and axon-glial signaling, in addition to a role in osmoregulation[9,10] All these brain metabolites (Glu, Gln, GABA, and NAA), along with the others, can be measured and quantified in living subjects by means of non-invasive neuroimaging methods including proton magnetic resonance spectroscopy (1H-MRS)[11] and chemical exchange saturation transfer (CEST)[12]. The goals of this study were to evaluate the neuron-glia integrity in living rats by non-invasive neuroimaging methods and to demonstrate the substructure of neuron-astrocyte and neuron-OL entities at cellular and molecular levels. For the first time we measured the integrity of neuron-glia entities in brains of living rats by non-invasive neuroimaging techniques of 1H-MRS, CEST of glutamate (GluCEST), and diffusion tensor imaging (DTI). This study presented the behavioral data from open field test that measures locomotor activity, exploratory behavior, and anxiety level of subjects

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