title: Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.
abstract: Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2) that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive) control, and a 90-min tail suspension was used as a stress (negative) control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC), ventromedial hypothalamus (VMH), and brain stem (BS). We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.
authors.affiliation: Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Joon W
authors.initials: JW
authors.lastname: Shim
authors.affiliation: Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, United States of America.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Dodge
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, United States of America.
authors.forename: Max A
authors.initials: MA
authors.lastname: Hammond
authors.affiliation: Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, United States of America ; Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wallace
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America ; Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
authors.affiliation: Department of Biomedical Engineering, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, United States of America ; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, United States of America.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yokota
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D005080:Exercise Test; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D015870:Gene Expression; D006614:Hindlimb / Q000502:physiology*; D019417:Hindlimb Suspension; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013312:Stress, Physiological; D014365:Tryptophan Hydroxylase / Q000235:genetics* / Q000378:metabolism; D016474:Weight-Bearing
chemical_list: D012333:RNA, Messenger; D012701:Serotonin; C487802:Tph2 protein, mouse; D014365:Tryptophan Hydroxylase