Alpha-9 nicotinic acetylcholine receptors mediate hypothermic responses elicited by provocative motion in mice

Tu, Longlong; Poppi, Lauren A.; Rudd, John A.; Cresswell, Ethan T; Dw, Smith; Brichta, Alan M.; Nalivaiko, Eugene

doi:10.1016/j.physbeh.2017.03.012

Cited by 25 publications

(33 citation statements)

References 31 publications

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“…In initial studies, it was concluded that the deletion of α9 was sufficient to render the α9α10 nAChR incapable of carrying current (Vetter et al, 2007 ; Taranda et al, 2009 ). Subsequent studies comparing α9 KOs with WTs (e.g., Mohammadi and Christie, 2014 ; Terreros et al, 2016 ; Mohammadi et al, 2017 ; Tu et al, 2017 ), have typically not used α10 KO mice, but presumed that deletion of α9 is equivalent to a deletion of the α9α10 receptor. Thus, any contribution of α10 would not have been detected.…”

Section: Discussionmentioning

confidence: 99%

Generation and Characterization of α9 and α10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background

et al. 2017

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We generated constitutive knockout mouse models for the α9 and α10 nicotinic acetylcholine receptor (nAChR) subunits by derivation from conditional knockouts by breeding with CRE deleter mice. We then backcrossed them onto a C57BL/6J genetic background. In this manuscript, we report the generation of the strains and an auditory phenotypic characterization of the constitutive α9 and α10 knockouts and a double α9α10 constitutive knockout. Although the α9 and α10 nAChR subunits are relevant to a number of physiological measures, we chose to characterize the mouse with auditory studies to compare them to existing but different α9 and α10 nAChR knockouts (KOs). Auditory brainstem response (ABR) measurements and distortion product otoacoustic emissions (DPOAEs) showed that all constitutive mouse strains had normal hearing. DPOAEs with contralateral noise (efferent adaptation measurements), however, showed that efferent strength was significantly reduced after deletion of both the α9 and α10 subunits, in comparison to wildtype controls. Animals tested were 3–8 weeks of age and efferent strength was not correlated with age. Confocal studies of single and double constitutive KOs showed that all KOs had abnormal efferent innervation of cochlear hair cells. The morphological results are similar to those obtained in other strains using constitutive deletion of exon 4 of α9 or α10 nAChR. The results of our physiological studies, however, differ from previous auditory studies using a α9 KO generated by deletion of the exon 4 region and backcrossed onto a mixed CBA/CaJ X 129Sv background.

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Section: Discussionmentioning

confidence: 99%

Generation and Characterization of α9 and α10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background

et al. 2017

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“…Nevertheless, any potential contribution of an increase in respiratory rate with links to forebrain functioning (e.g., anxiety or “nausea”) needs to be made cautiously since such changes also occur prior to emetic episodes induced by electrical or chemical stimulation of brain pathways and can be seen in anesthetized and decerebrate animals (Bradley et al, 1987; Koga and Fukuda, 1990; Howard and Sears, 1991). As regards GMA, motion induced a reduction in normogastria (Percie du Sert et al, 2010) and there was also a slight fall in body temperature (Ngampramuan et al, 2014; Tu et al, 2017); the latter effect has been documented consistently across several species and has been suggested to be associated with nausea (Nalivaiko et al, 2014). Whilst motion clearly affected the % of power partitioning of GMA, MFDFA revealed that the actual structure of the slow waves themselves did not appear to be disrupted.…”

Section: Discussionmentioning

confidence: 99%

Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew)

Dieser

et al. 2017

Front. Physiol.

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Motion sickness occurs under a variety of circumstances and is common in the general population. It is usually associated with changes in gastric motility, and hypothermia, which are argued to be surrogate markers for nausea; there are also reports that respiratory function is affected. As laboratory rodents are incapable of vomiting, Suncus murinus was used to model motion sickness and to investigate changes in gastric myoelectric activity (GMA) and temperature homeostasis using radiotelemetry, whilst also simultaneously investigating changes in respiratory function using whole body plethysmography. The anti-emetic potential of the highly selective histamine H1 receptor antagonists, mepyramine (brain penetrant), and cetirizine (non-brain penetrant), along with the muscarinic receptor antagonist, scopolamine, were investigated in the present study. On isolated ileal segments from Suncus murinus, both mepyramine and cetirizine non-competitively antagonized the contractile action of histamine with pKb values of 7.5 and 8.4, respectively; scopolamine competitively antagonized the contractile action of acetylcholine with pA2 of 9.5. In responding animals, motion (1 Hz, 4 cm horizontal displacement, 10 min) increased the percentage of the power of bradygastria, and decreased the percentage power of normogastria whilst also causing hypothermia. Animals also exhibited an increase in respiratory rate and a reduction in tidal volume. Mepyramine (50 mg/kg, i.p.) and scopolamine (10 mg/kg, i.p.), but not cetirizine (10 mg/kg, i.p.), significantly antagonized motion-induced emesis but did not reverse the motion-induced disruptions of GMA, or hypothermia, or effects on respiration. Burst analysis of plethysmographic-derived waveforms showed mepyramine also had increased the inter-retch+vomit frequency, and emetic episode duration. Immunohistochemistry demonstrated that motion alone did not induce c-fos expression in the brain. Paradoxically, mepyramine increased c-fos in brain areas regulating emesis control, and caused hypothermia; it also appeared to cause sedation and reduced the dominant frequency of slow waves. In conclusion, motion-induced emesis was associated with a disruption of GMA, respiration, and hypothermia. Mepyramine was a more efficacious anti-emetic than cetirizine, suggesting an important role of centrally-located H1 receptors. The ability of mepyramine to elevate c-fos provides a new perspective on how H1 receptors are involved in mechanisms of emesis control.

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“…Notably, there is a body temperature decrease in animals subjected to restraint or immobilization stress. Further, other stress forms, including food deprivation [72], hypoxia [73], and rotation [74], lead to torpor and decreased oxygen consumption. Hypergravity-induced hypothermia could result from two synergistic effects; namely, increased heat dissipation and reduced thermogenesis.…”

Section: Gravity Sickness and Hypothermiamentioning

confidence: 99%

“…Additionally, some studies have suggested the involvement of the vestibular efferents, which terminate on the vestibular hair cells and release acetylcholine. Shaking-induced hypothermia is suppressed in mice lacking the α9 cholinoreceptor subunit, which is predominantly expressed in the vestibular hair cells [74]. In humans, rotation with enhanced head movements, which facilitates motion sickness, was reported to result in decreased body temperature compared to that after rotation only [87].…”

Section: Gravity Sickness and Hypothermiamentioning

confidence: 99%

Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment

et al. 2020

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The peripheral vestibular organs are sensors for linear acceleration (gravity and head tilt) and rotation. Further, they regulate various body functions, including body stability, ocular movement, autonomic nerve activity, arterial pressure, body temperature, and muscle and bone metabolism. The gravitational environment influences these functions given the highly plastic responsiveness of the vestibular system. This review demonstrates that hypergravity or microgravity induces changes in vestibular-related physiological functions, including arterial pressure, muscle and bone metabolism, feeding behavior, and body temperature. Hopefully, this review contributes to understanding how human beings can adapt to a new gravitational environment, including the moon and Mars, in future.

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Alpha-9 nicotinic acetylcholine receptors mediate hypothermic responses elicited by provocative motion in mice

Cited by 25 publications

References 31 publications

Generation and Characterization of α9 and α10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background

Generation and Characterization of α9 and α10 Nicotinic Acetylcholine Receptor Subunit Knockout Mice on a C57BL/6J Background

Brain Activation by H1 Antihistamines Challenges Conventional View of Their Mechanism of Action in Motion Sickness: A Behavioral, c-Fos and Physiological Study in Suncus murinus (House Musk Shrew)

Understanding vestibular-related physiological functions could provide clues on adapting to a new gravitational environment

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