Ependymal cells and neurodegenerative disease: outcomes of compromised ependymal barrier function

Abstract

Within the CNS, ependymal cells form critical components of the blood-CSF barrier and the CSF-brain barrier. These barriers provide biochemical, immunological, and physical protection against the entry of molecules and foreign substances into the CSF while also regulating CSF dynamics, such as the composition, flow, and removal of waste from the CSF. Previous research has demonstrated that several neurodegenerative diseases, such as Alzheimer’s disease and multiple sclerosis, display irregularities in ependymal cell function, morphology, gene expression, and metabolism. Despite playing key roles in maintaining overall brain health, ependymal barriers are largely overlooked and understudied in the context of disease, thus limiting the development of novel diagnostic and treatment options. Therefore, this review explores the anatomical properties, functions, and structures that define ependymal cells in the healthy brain, as well as the ways in which ependymal cell dysregulation manifests across several neurodegenerative diseases. Specifically, we will address potential mechanisms, causes, and consequences of ependymal cell dysfunction and describe how compromising the integrity of ependymal barriers may initiate, contribute to, or drive widespread neurodegeneration in the brain.

MMCCI: multimodal integrative analysis of single-cell and spatial cell-type communications to uncover overarching and condition-specific ligand-receptor interaction pathways

“…Interactions within ependymal cells and oligodendrocytes were shown to decrease significantly with age, while interactions within astrocytes and from astrocytes to neurons significantly increased with age. This reflects the current understanding that the ependymal layer thins during aging and reactive astrocytes proliferate and interpose themselves within the ependymal cell layer [25, 26]. Oligodendrocyte numbers and function are also known to decrease with age while astrocyte interactions increase, which is shown in our findings [27, 28, 29].…”

“…In the aging brain, astrocytes were shown to become more active, not only increasing their interaction strength but also the types of LR interactions, which is consistent with the current understanding of the roles of astrocytes in aging [27,28,29,30,31,32,33,34,35]. The thinning of the ependymal layer expected in aging was also shown by the observed decrease in ependymal interactions in aging [25,26].…”

Cerebral furin deficiency causes hydrocephalus in mice

“…Ependymal cells are essential for neuronal development. 61 It is reported that hydrocephalus can be caused by mutations in MPDZ gene that leads to ependymal malformation, 62 and by deletion of SNX27 or YAP that impairs ependymal cell differentiation. 37 , 63 Importantly, in mutant hydrocephalus with hop gait (hyh) mice, 64 ependymal denudation develops before the onset of hydrocephalus.…”

Role of caveolin-1 in metabolic programming of fetal brain

“… 100 Deregulated ependyma can impair these process during brain development leading to increased risk for neurodegenerative diseases. 101 Cav1 is known to influence cell proliferation and death 11 , 24 , 102 by controlling specific apoptosis genes. 103 , 104 Cav1 is regarded as a master regulator of cellular senescence.…”