Psychiatric behaviors associated with cytoskeletal defects in radial neuronal migration

Abstract

Normal development of the cerebral cortex is an important process for higher brain functions, such as language, and cognitive and social functions. Psychiatric disorders, such as schizophrenia and autism, are thought to develop owing to various dysfunctions occurring during the development of the cerebral cortex. Radial neuronal migration in the embryonic cerebral cortex is a complex process, which is achieved by strict control of cytoskeletal dynamics, and impairments in this process are suggested to cause various psychiatric disorders. Our recent findings indicate that radial neuronal migration as well as psychiatric behaviors is rescued by controlling microtubule stability during the embryonic stage. In this review, we outline the relationship between psychiatric disorders, such as schizophrenia and autism, and radial neuronal migration in the cerebral cortex by focusing on the cytoskeleton and centrosomes. New treatment strategies for psychiatric disorders will be discussed.

FLRTing Neurons in Cortical Migration During Cerebral Cortex Development

“…During this phase, pyramidal neurons have to translate extracellular signals coming from substrates (neighboring neurons, ECM, radial glia fibers) and guidance cues into cytoskeletal arrangements and signal transduction modifications to follow their proper migratory route. This process is fundamental to establish the different cortical layers and appropriate cellular distribution, and thus alterations can lead to several types of cortical malformations including cortical heterotopias (subcortical and periventricular) and abnormal folding, such as lissencephaly, in humans (see Buchsbaum and Cappello, 2019;Subramanian et al, 2019 for recent reviews), that have been associated with several neuropsychiatric disorders such as schizophrenia and autism spectrum disorders (Fukuda and Yanagi, 2017;Guarnieri et al, 2018). Finally, recent studies in mouse and ferret models have demostrated the impact of neuronal migration on cortical folding.…”

Cannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration

“…The cerebral cortex is composed of a complex network of excitatory projection neurons and inhibitory interneurons that are generated, migrate to predetermined destination and establish specific synaptic connections through precisely orchestrated processes, and dysfunction during assembly may cause neuropsychiatric disorders such as lissencephaly, polymicrogyria and autism spectrum disorder [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. Neural progenitors undergoing repeated cycles of proliferation in the ventricular zone (VZ) undergo interkinetic nuclear translocation whereby the postmitotic nucleus moves within the vertically elongated cell body to the basal region of the VZ during the S phase of the cell cycle and then it returns to the apical region for mitosis [ 8 ].…”

A Peptide Link Between Human Cytomegalovirus Infection, Neuronal Migration, and Psychosis

“…Clinically, disruption of this process has been related not only to severe malformations of cortical development (lissencephaly, schizencephaly, neuronal eterotopia, polymicrogyria) (7) but also to psychosis (8)(9)(10). However, the relationship between macroand microscopic structural brain anomalies and psychosis appears to be unclear, and disruption of cellular function has been hypothesized (11,12).…”