Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain

Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear’s vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes

Effects of gravity changes on gene expression of BDNF and serotonin receptors in the mouse brain.

Spaceflight entails various stressful environmental factors including microgravity. The effects of gravity changes have been studied extensively on skeletal, muscular, cardiovascular, immune and vestibular systems, but those on the nervous system are not well studied. The alteration of gravity in ground-based animal experiments is one of the approaches taken to address this issue. Here we investigated the effects of centrifugation-induced gravity changes on gene expression of brain-derived neurotrophic factor (BDNF) and serotonin receptors (5-HTRs) in the mouse brain. Exposure to 2g hypergravity for 14 days showed differential modulation of gene expression depending on regions of the brain. BDNF expression was decreased in the ventral hippocampus and hypothalamus, whereas increased in the cerebellum. 5-HT1BR expression was decreased in the cerebellum, whereas increased in the ventral hippocampus and caudate putamen. In contrast, hypergravity did not affect gene expression of 5-HT1AR, 5-HT2AR, 5-HT2CR, 5-HT4R and 5-HT7R. In addition to hypergravity, decelerating gravity change from 2g hypergravity to 1g normal gravity affected gene expression of BDNF, 5-HT1AR, 5-HT1BR, and 5-HT2AR in various regions of the brain. We also examined involvement of the vestibular organ in the effects of hypergravity. Surgical lesions of the inner ear's vestibular organ removed the effects induced by hypergravity on gene expression, which suggests that the effects of hypergravity are mediated through the vestibular organ. In summary, we showed that gravity changes induced differential modulation of gene expression of BDNF and 5-HTRs (5-HT1AR, 5-HT1BR and 5-HT2AR) in some brain regions. The modulation of gene expression may constitute molecular bases that underlie behavioral alteration induced by gravity changes

Glucose Metabolic Changes in the Brain and Muscles of Patients with Nonspecific Neck Pain Treated by Spinal Manipulation Therapy: A [18F]FDG PET Study

Objective. The aim of this study was to investigate changes in brain and muscle glucose metabolism that are not yet known, using positron emission tomography with [18F]fluorodeoxyglucose ([18F]FDG PET). Methods. Twenty-one male volunteers were recruited for the present study. [18F]FDG PET scanning was performed twice on each subject: once after the spinal manipulation therapy (SMT) intervention (treatment condition) and once after resting (control condition). We performed the SMT intervention using an adjustment device. Glucose metabolism of the brain and skeletal muscles was measured and compared between the two conditions. In addition, we measured salivary amylase level as an index of autonomic nervous system (ANS) activity, as well as muscle tension and subjective pain intensity in each subject. Results. Changes in brain activity after SMT included activation of the dorsal anterior cingulate cortex, cerebellar vermis, and somatosensory association cortex and deactivation of the prefrontal cortex and temporal sites. Glucose uptake in skeletal muscles showed a trend toward decreased metabolism after SMT, although the difference was not significant. Other measurements indicated relaxation of cervical muscle tension, decrease in salivary amylase level (suppression of sympathetic nerve activity), and pain relief after SMT. Conclusion. Brain processing after SMT may lead to physiological relaxation via a decrease in sympathetic nerve activity

Effects of gravity changes on the mRNA expression of 5-HT1AR.

<p>The mRNA expression of 5-HT1A receptor in the medial prefrontal cortex (A), caudate putamen (B), amygdala (C), dorsal hippocampus (D), ventral hippocampus (E), hypothalamus (F), dorsal raphe (G) and cerebellum (H). 2<i>g</i>-14d:14-day exposure to 2<i>g</i>, 2<i>g</i>-14d+1<i>g</i>-3d:3-day recovery after 14-day exposure to 2<i>g</i>. * p<0.05, ** p<0.01.</p

Effects of gravity changes the mRNA expression of 5-HT2AR.

<p>The mRNA expression of 5-HT2A receptor in the medial prefrontal cortex (A), caudate putamen (B), amygdala (C), dorsal hippocampus (D), ventral hippocampus (E), hypothalamus (F), and cerebellum (G). 2<i>g</i>-14d:14-day exposure to 2<i>g</i>, 2<i>g</i>-14d+1<i>g</i>-3d:3-day recovery after 14-day exposure to 2<i>g</i>. * p<0.05, ** p<0.01.</p

Effects of gravity changes on the mRNA expression of 5-HT1BR.

<p>The mRNA expression of 5-HT1B receptor in the medial prefrontal cortex (A), caudate putamen (B), amygdala (C), dorsal hippocampus (D), ventral hippocampus (E), hypothalamus (F), and cerebellum (G). 2<i>g</i>-14d:14-day exposure to 2<i>g</i>, 2<i>g</i>-14d+1<i>g</i>-3d:3-day recovery after 14-day exposure to 2<i>g</i>. * p<0.05, ** p<0.01.</p

Effects of gravity change on the mRNA expression in the vestibular lesioned mice.

<p>The mRNA expression of BDNF in the ventral hippocampus (A), hypothalamus (B) and cerebellum (C), and that of 5-HT1B receptor in the caudate putamen (D), ventral hippocampus (E) and cerebellum (F). VL; Control: Vestibular lesioned mice under normal gravity, VL; 2<i>g</i>-14d: Vestibular lesioned mice exposed to 2<i>g</i> for 14 days.</p

Effects of vestibular lesion on the mRNA expression of BDNF and 5-HT1BR.

<p>The mRNA expression of BDNF in the ventral hippocampus (A), hypothalamus (B) and cerebellum (C) and that of 5-HT1B receptor in the caudate putamen (D), ventral hippocampus (E) and cerebellum (F). Control: mice with intact vestibular organ, VL: mice with vestibular lesion. 0.05≦ # p<0.07, * p<0.05.</p