Atrial Natriuretic Peptide Alleviates Motion Sickness Potentially through Regulating Endolymph Volume in the Inner Ear Increased by Arginine Vasopressin.

INTRODUCTION: Dimenhydrinate and scopolamine are frequently used drugs, but they cause drowsiness and performance decrement. Therefore, it is crucial to find peripheral targets and develop new drugs without central side effects. This study aimed to investigate the anti-motion sickness action and inner ear-related mechanisms of atrial natriuretic peptide (ANP). METHODS: Endolymph volume in the inner ear was measured with magnetic resonance imaging and expression of AQP2 and p-AQP2 was detected with Western blot analysis and immunofluorescence method. RESULTS: Both rotational stimulus and intraperitoneal arginine vasopressin (AVP) injection induced conditioned taste aversion (CTA) to 0.15% sodium saccharin solution and an increase in the endolymph volume of the inner ear. However, intraperitoneal injection of ANP effectively alleviated the CTA behaviour and reduced the increase in the endolymph volume after rotational stimulus. Intratympanic injection of ANP also inhibited rotational stimulus-induced CTA behaviour, but anantin peptide, an inhibitor of ANP receptor A (NPR-A), blocked this inhibitory effect of ANP. Both rotational stimulus and intraperitoneal AVP injection increased the expression of AQP2 and p-AQP2 in the inner ear of rats, but these increases were blunted by ANP injection. In in vitro experiments, ANP addition decreased AVP-induced increases in the expression and phosphorylation of AQP2 in cultured endolymphatic sac epithelial cells. CONCLUSION: Therefore, the present study suggests that ANP could alleviate motion sickness through regulating endolymph volume of the inner ear increased by AVP, and this action of ANP is potentially mediated by activating NPR-A and antagonising the increasing effect of AVP on AQP2 expression and phosphorylation.

Association of Lymphatic Fluid Volume in the Inner Ear of Beagle Dogs with the Susceptibility to Motion Sickness.

BACKGROUND: This study aimed to quantify total lymphatic fluid spaces of the inner ears volumetrically in the dog in order to find a correlation between the lymphatic volume of the inner ears and motion sickness susceptibility. METHODS: A total of 16 healthy adult Beagle dogs were used to delineate the lymphatic fluid spaces of inner ears by magnetic resonance imag- ing with a 3-dimensional-constructive interference steady-state sequence. Manual segmentation was applied for 3-dimensional reconstruction and volumetric quantification of total lymphatic space. The susceptibility of Beagle dogs to motion sickness was judged by latency of vomiting during rotatory stimulus. RESULTS: The volume range of total fluid space in the vestibule and cochlea of Beagle dogs is 55.07 ± 6.2 mm3. There is no significant difference in the total lymphatic volume of bilateral inner ears between 2 different motion sickness susceptibility groups (i.e., sensitive group and insensi- tive group), but the difference of lymphatic volume in the cochlea and vestibule between bilateral inner ears in insensitive group is greater than that of sensitive group. Moreover, a significant positive correlation was found between bilateral inner ear difference in lymphatic volume and vomiting latency. CONCLUSION: Magnetic resonance imaging could be used as a method to evaluate the inner ear lymphatic fluid volume of Beagle dogs with different susceptibilities to motion sickness, through which we found that motion sickness susceptibility is related to the difference in lymphatic volume in the vestibule and cochlea between bilateral inner ears, and the larger the volume difference, the lower the susceptibility.

The Aptamer Ob2, a novel AChE inhibitor, restores cognitive deficits and alleviates amyloidogenesis in 5×FAD transgenic mice.

Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer's disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5×FAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5×FAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5×FAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Aß by lowering the expression of ß-secretase (BACE1), and activation of astrocytes in the brains of 5×FAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD.