Motion sickness brain circuit may provide new options for treating obesity
“When Dr. Longlong Tu, a postdoctoral fellow in my lab, proposed to investigate the brain circuits involved in motion sickness, a condition for which he is highly susceptible, I was not very excited about the idea because it’s not one of the main interests of my lab,” said Dr. Yong Xu, professor of pediatrics – nutrition and associate director for basic sciences at the USDA/ARS Children’s Nutrition Research Center at Baylor. “However, I became more interested and supported Tu’s idea when he explained the emerging evidence suggesting a link between motion sickness and metabolic balance, which is one of my research interests.”
The Xu lab works with mouse models to investigate how the brain regulates metabolism and how this may be related to obesity and inform the development of more effective obesity drugs. Mouse models offer an abundance of molecular and genetic tools, as well as relevant behavioral assays to elucidate the neural mechanisms underlying physiological responses. But there was a challenge – mice are incapable of vomiting, one of the main manifestations of motion sickness in people.
Interestingly, mice and humans subjected to motion sickness stimuli, such as experiencing horizontal motion back and forth for some time, show hypothermia, a reduction in body temperature. “This allowed us to develop a mouse model of motion sickness in which we measured core body temperature, physical activity and brain activity as the animals experienced motion stimuli,” Xu explained.
The team reported in a study published in Nature Metabolism that motion activates glutamatergic neurons – neurons that produce glutamate, the primary excitatory neurotransmitter in the central nervous system – in the medial vestibular nucleus parvocellular part (MVePCGlu) of the brain. Activation of these neurons is required and sufficient to mediate motion-induced thermal adaptations. The researchers validated the model by showing that motion sickness-induced hypothermia does not occur when the mice are given the anti-nausea drug scopolamine.
“We further studied this motion sickness circuit by inhibiting the MVePCGlu neurons in the absence of motion stimuli,” Xu said. “Inhibiting these neurons led to an increase in body temperature, along with increased physical activity. These physiological alterations suggest that chronic inhibition of MVePCGlu neurons may result in a higher energy expenditure in mice.”
When the researchers investigated the potential metabolic benefits of the chronic inhibition of MVePCGlu neurons they found that, although the mice ate more, they gained less weight and exhibited better glucose tolerance and enhanced insulin sensitivity, physiological responses associated with better health.
These results highlight the underappreciated function of the brain’s vestibular system in metabolic balance and further raise the possibility that better understanding of the neural basis for thermoregulation during motion sickness may provide unconventional targets for the treatment of obesity,” Xu said.
And for first author Tu, the findings offer hope that a better understanding of the brain circuit for motion sickness could also lead to improved medications for his condition.
Other contributors to this work include Xing Fang, Yongjie Yang, Meng Yu, Hailan Liu, Hesong Liu, Na Yin, Jonathan C. Bean, Kristine Marie Conde, Mengjie Wang, Yongxiang Li, Olivia Z. Ginnard, Qingzhuo Liu, Yuhan Shi, Junying Han, Yi Zhu, Makoto Fukuda, Qingchun Tong, Benjamin Arenkiel, Mingshan Xue, Yang He and Chunmei Wang. The authors are affiliated with one or more of the following institutions: Baylor College of Medicine, the University of Texas Health Science Center at Houston and the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.
This study was supported by grants from the NIH (P01DK113954, R01DK115761, R01DK117281, R01DK125480 and R01DK120858, R01DK104901, R01DK12665, R01MH117089), USDA/CRIS (51000-064-01S, 51000-064-02S, 3092-51000-062-04(B)S, 1F32DK13868501A1), the McKnight Foundation and an American Heart Association Postdoctoral Fellowship (2020AHA000POST000204188).
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