Potential of Multiscale Astrocyte Imaging for Revealing Mechanisms Underlying Neurodevelopmental Disorders

Abstract

Astrocytes provide trophic and metabolic support to neurons and modulate circuit formation during development. In addition, astrocytes help maintain neuronal homeostasis through neurovascular coupling, blood–brain barrier maintenance, clearance of metabolites and nonfunctional proteins via the glymphatic system, extracellular potassium buffering, and regulation of synaptic activity. Thus, astrocyte dysfunction may contribute to a myriad of neurological disorders. Indeed, astrocyte dysfunction during development has been implicated in Rett disease, Alexander’s disease, epilepsy, and autism, among other disorders. Numerous disease model mice have been established to investigate these diseases, but important preclinical findings on etiology and pathophysiology have not translated into clinical interventions. A multidisciplinary approach is required to elucidate the mechanism of these diseases because astrocyte dysfunction can result in altered neuronal connectivity, morphology, and activity. Recent progress in neuroimaging techniques has enabled noninvasive investigations of brain structure and function at multiple spatiotemporal scales, and these technologies are expected to facilitate the translation of preclinical findings to clinical studies and ultimately to clinical trials. Here, we review recent progress on astrocyte contributions to neurodevelopmental and neuropsychiatric disorders revealed using novel imaging techniques, from microscopy scale to mesoscopic scale.

Research Progress on the Role of RNA m6A Modification in Glial Cells in the Regulation of Neurological Diseases

“…Microglia are activated, to perform synapsis pruning and phagocytosis of broken neurons, and inhibit the release of neurotrophic factors, to induce the death of gray matter neurons [ 112 ]. The autopsy results of some SCZ patients showed increased astrocytes, which might be associated with neurotransmitter response, synaptic dysfunction, and inflammatory response [ 113 , 114 ].…”

Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders

“…There are numerous factors that are involved in many brain disorders such as oxidative stress, neuroinflammation, and apoptosis, which could be the reason for the accumulation of extracellular amyloid-beta peptides [ 24 ]. It has been found that tauopathy in animals is caused by an impaired glymphatic system [ 25 ], and neuroinflammation, cytokines, chemokines, and the complement system also play a major role in MDD [ 26 ].…”

Translational Magnetic Resonance Imaging in Autism Spectrum Disorder From the Mouse Model to Human

“…Depending on the method of resting-state analysis, functional connectivity analysis can indirectly indicate several neural networks, which are strongly functionally connected at rest and are related to cognitive function ( Li et al, 2017 ). Diffusion tensor imaging (DTI) detects the displacement of a water molecule in white matter ( Le Bihan et al, 2001 ; Kumamoto and Tsurugizawa, 2021 ) and can indirectly measure the degree of anisotropy and the structural orientation of projecting fiber ( Basser et al, 1994 ; Figure 1B ). DTI estimates the mean diffusivity (MD) and fractional anisotropy (FA), indicating the degree of water diffusion in the tissue and degree of anisotropy of the fiber projection, respectively ( Peeters et al, 2001 ).…”