Alcohol consumption impairs the ependymal cilia motility in the brain ventricles

Alzahra J Al Omran,Alexander Wisner,Yusuf S Althobaiti,Wissam A Aboualaiwi,Youssef Sari,Surya M Nauli,Hannah C Saternos

doi:10.1038/s41598-017-13947-3

Alzahra J Al Omran, Alexander Wisner + Show 5 more

Open Access

https://doi.org/10.1038/s41598-017-13947-3

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Abstract

Ependymal cilia protrude into the central canal of the brain ventricles and spinal cord to circulate the cerebral spinal fluid (CSF). Ependymal cilia dysfunction can hinder the movement of CSF leading to an abnormal accumulation of CSF within the brain known as hydrocephalus. Although the etiology of hydrocephalus was studied before, the effects of ethanol ingestion on ependymal cilia function have not been investigated in vivo. Here, we report three distinct types of ependymal cilia, type-I, type-II and type-III classified based upon their beating frequency, their beating angle, and their distinct localization within the mouse brain-lateral ventricle. Our studies show for the first time that oral gavage of ethanol decreased the beating frequency of all three types of ependymal cilia in both the third and the lateral rat brain ventricles in vivo. Furthermore, we show for the first time that hydin, a hydrocephalus-inducing gene product whose mutation impairs ciliary motility, and polycystin-2, whose ablation is associated with hydrocephalus are colocalized to the ependymal cilia. Thus, our studies reinforce the presence of three types of ependymal cilia in the brain ventricles and demonstrate the involvement of ethanol as a risk factor for the impairment of ependymal cilia motility in the brain.

Highlights

The motile ciliated cells are ubiquitous in the lung airways, the fallopian tubes in the uterus, the efferent ducts in the testes and sperm tail, as well as in the brain ventricles and spinal cord canal
The cerebral spinal fluid (CSF) flows in a unilateral direction starting in the lateral ventricle, moving through the third ventricle, and the fourth ventricle where it passes into the subarachnoid space insulating the brain and spinal cord
We show for the first time that oral gavage of ethanol alters the beating of ependymal cilia in the rat brain lateral and third ventricles

Summary

Introduction

The motile ciliated cells are ubiquitous in the lung airways, the fallopian tubes in the uterus, the efferent ducts in the testes and sperm tail, as well as in the brain ventricles and spinal cord canal. This disparity leads to an extreme accumulation of fluid causing the brain ventricular cavities and the subarachnoid spaces to expand in response to the increase in CSF1,2. Hy3/hy[3] mutant mice show early hydrocephalous onset and an enlargement of the lateral and third ventricles, as a result of abnormal CSF flow caused by the impairment of cilia movement. The beating frequency of ependymal cilia in the hydin mutant mice declines significantly due to changes in the location of the central pair microtubules leading to ineffective fluid movement[13]. Polycystin-2 serves as a sensory protein that detects changes in fluid flow within the respiratory ciliated cells and contributes to the development of brain planar cell polarity (PCP) and prevention of hydrocephalus[18]

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