Abstract
Ependymal cells line the brain ventricles and separate the CSF from the underlying neuronal tissue. The function of ependymal cilia is largely unclear however they are reported to be involved in the regulation of CSF homeostasis and host defence against pathogens. Here we present data that implicates a role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the inhibition of ependymal ciliary function, and also that the PACAP effects are not entirely dependent on adenylyl cyclase activation. Primary ependymal cultures were treated with increasing doses of PACAP27 or adenylyl cyclase toxin (ACT), and ciliary beating was recorded using high-speed digital video imaging. Ciliary beat frequency (CBF) and amplitude were determined from the videos. Ependymal CBF and ciliary amplitude were attenuated by PACAP27 in a concentration- and time-dependent manner. The peptide antagonist PACAP6-27 blocked PACAP27-induced decreases in amplitude and CBF. Treatment with ACT caused a decrease in amplitude but had no effect on CBF, this suggests that the inhibition of CBF and amplitude seen with PACAP27 may not be completely explained by G(s)-AC-cAMP pathway. We present here the first observational study to show that activation of PAC1 receptors with PACAP27 has an important role to play in the regulation of ependymal ciliary function.
Highlights
Ependymal cells lining the ventricular cavities form a protective interface between brain parenchyma and the circulating cerebrospinal fluid (CSF)
PACAP27 caused a decrease in Ciliary beat frequency (CBF) and amplitude
This study aimed to clarify whether pituitary adenylate cyclase-activating polypeptide (PACAP) has a role in controlling ependymal ciliary function
Summary
Ependymal cells lining the ventricular cavities form a protective interface between brain parenchyma and the circulating cerebrospinal fluid (CSF). Ependymal cells bear approximately 40 motile cilia per cell which beat in the coordinated pattern at approximately 40 Hz (Del Bigio, 1995; O'Callaghan et al, 1999) that rapidly move CSF adjacent to the ventricular walls. Ependymal cilia have been shown to play an important role in host defence against pathogens (Hirst et al, 2003; Hirst et al, 2000; Mohammed et al, 1999). A recent study (Sawamoto et al, 2006) has shown that ependymal cilia are responsible for the formation of gradients of CSF guidance molecules that direct neuroblast movement in the brain parenchyma. Few studies have addressed the question of hormonal regulation of the ciliary function
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