研究チーム

Research Programs

Autonomic Neuroscience

 

Members

Theme Leader :
Harumi Hotta, Ph.D.
Researcher :
Sae Uchida, Ph.D., Nobuhiro Watanabe, Ph.D.
Adjunct Researcher :
Akiko Onda, Ph.D.

Keywords

autonomic nervous system, hormone, somatosensory stimulation, aging, basal forebrain cholinergic system, acetylcholine, blood flow, nerve growth factor,

Major Research Titles

  1. Autonomic nervous system function in the elderly
  2. Cholinergic neurons and cognitive function

Profile

We perform research activity using electrophysiological and imaging techniques mainly on anesthetized animals (and humans in some cases).
Our goal is to characterize autonomic function in the elderly, and to identify strategies to regulate autonomic nervous system activity. We have studied neural mechanisms for somatosensory stimulation to influence autonomic functions. Recently we showed: (1) a method of subtle skin stimulation that suppresses micturition reflex via activating the endogenous opioid system, may be applicable to improve incontinence; (2) a novel role of ovarian sympathetic nerve is ovarian estradiol secretion regulation and the nerve activity is facilitated by noxious skin stimulation, causing estradiol secretion decrease.
Cognitive decline in patients with dementia and the elderly is related to the dysfunction of cholinergic basal forebrain neurons. Another goal is to define the roles of cholinergic system in the regulation of cortical arteries and nerve growth factor (NGF) secretion. We showed: (1) tactile stimulation activates the cholinergic system, thereby facilitates cerebral blood flow and NGF secretion; (2) chronic nicotine infusion enhances responses of cortical ACh release and vasodilation during basal forebrain stimulation in adult, but not aged, rats, suggesting that a reduction of nicotinic receptors may relate to dysfunction of the cholinergic system during aging.

References

1. Uchida, S., Kagitani, F. (2016) Sympathetic regulation of ovarian functions under chronic estradiol treatment in rats. Auton. Neurosci., in press.

2. Iimura, K., Watanabe, N., Masunaga, K., Miyazaki, S., Hotta, H., Kim, H., Hisajima, H., Takahashi, H., Kasuya, Y. (2016) Effects of a gentle, self-administered stimulation of perineal skin for nocturia in elderly women: a randomized, placebo-controlled, double-blind crossover trial. PLoS One, 11, e0151726

3. Hotta, H., Watanabe, N. (2015) Gentle mechanical skin stimulation inhibits micturition contractions via the spinal opioidergic system and by decreasing both ascending and descending transmissions of the micturition reflex in the spinal cord. PLoS One, 10, e0135185.

4. Uchida, S., Kagitani, F., Hotta, H. (2015) Afferent fibers involved in the bradykinin-induced cardiovascular reflexes from the ovary in rats. Auton. Neurosci., 193, 57-62

5. Watanabe, N., Piché, M., Hotta, H. (2015) Types of skin afferent fibers and spinal opioid receptors that contribute to touch-induced inhibition of heart rate changes evoked by noxious cutaneous heat stimulation. Mol. Pain, 11, 4

6. Uchida, S., Kagitani, F. (2014) Effect of acupuncture-like stimulation on cortical cerebral blood flow in aged rats. J Physiol Sci, 65, 67-75

7. Piché, M., Watanabe, N., Sakata, M., Oda, K., Toyohara, J., Ishii, K., Ishiwata, K., Hotta, H. (2014) Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation. Neurosci. Res., 81-82, 78-84

8. Hotta, H., Watanabe, N., Piché, M., Hara, S., Yokawa, T., Uchida, S. (2014) Non-noxious skin stimulation activates the nucleus basalis of Meynert and promotes NGF secretion in the parietal cortex via nicotinic ACh receptors. J. Physiol. Sci., 64, 253-260

9. Uchida, S., Kagitani, F. (2014) Effects of electrical stimulation of autonomic nerves to the ovary on the ovarian testosterone secretion rate in rats. Auton. Neurosci., 180, 48-52

10. Piché, M., Watanabe, N., Hotta, H. (2014) Regulation of gastric motility and blood flow during acute nociceptive stimulation of the paraspinal muscles in urethane-anaesthetised rats. J. Physiol. Sci., 64, 37-46

11. Hotta, H., Masamoto, K., Uchida, S., Sekiguchi, Y., Takuwa, H., Kawaguchi, H., Shigemoto, K., Sudo, R., Tanishita, K., Ito, H., Kanno, I. (2013) Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex. J Cereb Blood Flow Metab., 33, 1440-1447

12. Watanabe, N., Ishii, K., Hotta, H., Oda, K., Sakata, M., Toyohara, J., Ishiwata, K. (2013) Differential human brain activity induced by two perceptually indistinguishable gentle cutaneous stimuli. Neuroreport, 24, 425-430

13. Uchida, S., Hotta, H., Misawa, H., Kawashima, K. (2013) The missing link between long-term stimulation of nicotinic receptors and the increases of acetylcholine release and vasodilation in the cerebral cortex of aged rats. J Physiol Sci., 63, 95-101

14. Uchida, S., Kagitani, F., Hotta, H. (2012) Reflex modulation of ovarian estradiol secretion by noxious mechanical stimulation of a hindpaw in anesthetized rats. Auton. Neurosci., 171, 14-20

15. Naggar, I., Uchida, S., Kamran, H., Lazar, J., Stewart, M. (2012) Autonomic boundary conditions for ventricular fibrillation and their implications for a novel defibrillation technique. J Physiol Sci., 62, 479-492

16. Watanabe, N., Miyazaki, S., Mukaino, Y., Hotta, H. (2012) Effect of gentle cutaneous stimulation on heat-induced autonomic response and subjective pain intensity in healthy humans. J Physiol Sci., 62, 343-350

17. Hotta, H., Masunaga, K., Miyazaki, S., Watanabe, N., Kasuya, Y. (2012) A gentle mechanical skin stimulation technique for inhibition of micturition contractions of the urinary bladder. Auton. Neurosci., 167, 12-20.

18. Hanada, T., Uchida, S., Hotta, H., Aikawa, Y. (2011) Number, size, conduction, and vasoconstrictor ability of unmyelinated fibers of the ovarian nerve in adult and aged rats. Auton. Neurosci., 164, 6-12.

19. Watanabe, N., Uchida, S., Hotta, H. (2011) Age-related change in the effect of gentle mechanical cutaneous stimulation on the somato-cardiac sympathetic C-reflex. J. Physiol. Sci., 61, 287-91.

20. Hotta, H., Uchida, S., Kagitani, F., Maruyama, N. (2011) Control of cerebral cortical blood flow by stimulation of basal forebrain cholinergic areas in mice. J. Physiol. Sci., 61, 201-209

21. Kagitani, F., Uchida, S., Hotta, H. (2011) The role of alpha adrenoceptors in the vascular and estradiol secretory responses to stimulation of the superior ovarian nerve. J. Physiol. Sci., 61, 247-251

22. Uchida, S., Hotta, H., Misawa, H., Kawashima, K. (2011) Sustained subcutaneous infusion of nicotine enhances cholinergic vasodilation in the cerebral cortex induced by stimulation of the nucleus basalis of Meynert in rats. Eur. J. Pharmacol., 654,235-240

23. Gotoh, M., Hotta, H., Murakami-Murofushi, K. (2010) Effects of cyclic phosphatidic acid on delayed neuronal death following transient ischemia in rat hippocampal CA1. Eur. J. Pharmacol., 649, 206-209

24. Piché, M., Uchida, S., Hara, S., Aikawa, Y., Hotta, H. (2010) Modulation of somatosensory-evoked cortical blood flow changes by GABAergic inhibition of the nucleus basalis of Meynert in urethane-anesthetized rats. J. Physiol., 588 (Pt 12), 2163-2171.

25. Hotta, H., Watanabe, N., Orman, R., Stewart, M. (2010) Efferent and afferent vagal actions on cortical blood flood flow and kainic acid-induced seizure activity in urethanized rats. Auton. Neurosci., 156, 144-148.

26. Fischer, M.J., Uchida, S., Messlinger, K. (2010) Measurement of meningeal blood vessel diameter in vivo with a plug-in for ImageJ. Microvasc. Res., 80,258-266

27. Hotta, H., Schmidt, R.F., Uchida, S., Watanabe, N. (2010) Gentle mechanical skin stimulation inhibits the somatocardiac sympathetic C-reflex elicited by excitation of unmyelinated C-afferent fibers. Europ. J. Pain, 14, 806-813.

28. Uchida, S., Kagitani, F., Watanabe, N., Hotta, H. (2010) Sympatho-inhibitory response of the heart as a result of short-term acupuncture-like stimulation of the rat hindlimb is not augmented when sympathetic tone is high due to hypercapnia. J. Physiol. Sci., 60: 221-225.

29. Hotta, H., Lazar, J., Orman, R., Koizumi, K., Shiba, K., Kamran, H., Stewart, M. (2009) Vagus nerve stimulation-induced bradyarrhythmias in rats. Auton. Neurosci., 151: 98-105.

30. Uchida, S., Hotta, H., Kawashima, K. (2009) Long-term nicotine treatment reduces cerebral cortical vasodilation mediated by α4β2-like nicotinic acetylcholine receptors in rats. Eur. J. Pharmacol., 609, 100-104.

31. Shiba, K., Machida, T., Uchida, S., Hotta, H. (2009) Sympathetic neural regulation of olfactory bulb blood flow in adult and aged rats. Auton. Neurosci., 147, 75-79.

32. Hotta, H., Koizumi, K., Stewart, M. (2009) Cardiac sympathetic nerve activity during kainic acid-induced limbic cortical seizures in rats. Epilepsia, 50, 923-927.

33. Hotta, H., Kagitani, F., Kondo, M., Uchida, S. (2009) Basal forebrain stimulation induces NGF secretion in ipsilateral parietal cortex via nicotinic receptor activation in adult, but not aged rats. Neurosci. Res., 63, 122-128.

34. Uchida, S., Kagitani, F., Hotta, H. (2008) Mechanism of the reflex inhibition of heart rate elicited by acupuncture-like stimulation in anesthetized rats. Auton. Neurosci., 143, 12-19.

35. Kagitani, F., Uchida, S., Hotta, H. (2008) Effects of electrical stimulation of the superior ovarian nerve and the ovarian plexus nerve on the ovarian estradiol secretion rate in rats. J. Physiol. Sci., 58, 133-138.

36. Uchida, S., Shimura, M., Ohsawa, H., Suzuki, A. (2007) Neural mechanism of bradycardiac responses elicited by acupuncture-like stimulation to a hind limb in anesthetized rats. J. Physiol. Sci., 57, 377-382.

37. Hotta, H., Uchida, S., Kagitani, F. (2007) Stimulation of the nucleus basalis of Meynert produces an increase in the extracellular release of nerve growth factor in the rat cerebral cortex. J. Physiol. Sci., 57, 383-387.

38. Uchida, S., Hotta, H., Hanada, T., Okuno, Y., Aikawa, Y. (2007) Effects of thermal stimulation, applied to the hindpaw via a hot water bath, upon ovarian blood flow in anesthetized nonpregnant rats. J. Physiol. Sci., 57, 227-233.

39. Hotta, H., Uchida, S., Shiba, K. (2007) Cerebral cortical blood flow response during basal forebrain stimulation in cats. NeuroReport, 18, 809-812.

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