文章基本信息

标题：Two distinct evolutionary conserved neural degeneration pathways characterized in a colonial chordate
本地全文：下载
作者：Chiara Anselmi ; Mark Kowarsky ; Fabio Gasparini 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：29
DOI：10.1073/pnas.2203032119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance Loss of the brain’s functional ability is a common symptom of aging across diverse phyla. While the genetic and molecular mechanisms underlying mammalian neurodegeneration have been studied in depth, very little is known about the evolutionary origin of these traits and their involvement in loss of nervous system function in aged-invertebrate species. Here, we present Botryllus schlosseri, a marine colonial tunicate, as a model system for evolutionary neuroscience and the study of neurogenesis, neurodegeneration, and aging. The organism’s unique life cycle, as characterized by two distinct yet connected neurodegenerative pathways, offers a novel platform for comparative studies designed to identify the cellular and molecular mechanisms regulating such processes across phylogeny. Colonial tunicates are marine organisms that possess multiple brains simultaneously during their colonial phase. While the cyclical processes of neurogenesis and neurodegeneration characterizing their life cycle have been documented previously, the cellular and molecular changes associated with such processes and their relationship with variation in brain morphology and individual (zooid) behavior throughout adult life remains unknown. Here, we introduce Botryllus schlosseri as an invertebrate model for neurogenesis, neural degeneration, and evolutionary neuroscience. Our analysis reveals that during the weekly colony budding (i.e., asexual reproduction), prior to programmed cell death and removal by phagocytes, decreases in the number of neurons in the adult brain are associated with reduced behavioral response and significant change in the expression of 73 mammalian homologous genes associated with neurodegenerative disease. Similarly, when comparing young colonies (1 to 2 y of age) to those reared in a laboratory for ∼20 y, we found that older colonies contained significantly fewer neurons and exhibited reduced behavioral response alongside changes in the expression of 148 such genes (35 of which were differentially expressed across both timescales). The existence of two distinct yet apparently related neurodegenerative pathways represents a novel platform to study the gene products governing the relationship between aging, neural regeneration and degeneration, and loss of nervous system function. Indeed, as a member of an evolutionary clade considered to be a sister group of vertebrates, this organism may be a fundamental resource in understanding how evolution has shaped these processes across phylogeny and obtaining mechanistic insight.
关键词：encolonial chordateneurodegenerationregenerationagingneural stem cells