Nozomi Asaoka

From Yasunori Hayashi Laboratory
Jump to navigation Jump to search
Nozomi Asaoka.jpg

Bibliography

  • 2015 Graduated with a degree in Pharmaceutical Science, Faculty of Pharmaceutical Science, Kyoto University.
  • 2018 Ph.D. Graduate School of Pharmaceutical Science, Kyoto University. (Prof. Shuji Kaneko)
  • 2018-2021 Assistant Professor. Dept. Pharmacology, Graduate School of Medicine, Kyoto Prefectural University of Medicine. (Prof. Chihiro Yabe-Nishimura)
  • 2021-present Assistant Professor. Dept. Pharmacology, Graduate School of Medicine, Kyoto University. (Prof. Yasunori Hayashi)

Research topics

Regulation of dorsal raphe serotonergic neurons by pharmacological treatments for psychiatric disorders

The raphe serotonergic system plays an important role in regulating a wide variety of brain functions, such as mood and cognition. It is widely accepted that facilitation of serotonergic system is one of the effective therapeutic targets for mental illnesses. Long-term administration of selective serotonin reuptake inhibitors (SSRIs) are the first-choice therapies for treating major depression, anxiety disorders and obsessive-compulsive disorder; however, their mechanisms of action, especially why “long-term” administration is required, are still being elucidated. We have revealed “the effects of SSRIs and other therapeutic agents on raphe serotonergic neurons and their action mechanisms” by organotypic slice cultures, ex vivo electrophysiology and behavioral analysis. [1-7, 11]
While raphe serotonergic neurons have intrinsic pacemaker activity, synaptic inputs to these neurons are also critical regulators of serotonergic neuronal activity. Like most neurons, local GABAergic inhibitory inputs act as a brake on serotonergic neurons. We have reported that medications for mental disorders weaken GABAergic inhibition of serotonergic neurons and facilitate serotonergic intrinsic activity/serotonin release.

  • Olanzapine facilitates serotonergic function through inhibiting 5-HT6 receptors [4]

Clinical studies indicate that the combination of an SSRI and an atypical antipsychotic agent, such as olanzapine, can enhance the therapeutic efficacy for treatment-resistant depression. Olanzapine inhibited firing activity of raphe GABAergic interneurons and disinhibit serotonergic activity through 5-HT6 receptor inhibition.

  • Long-term administration of an SSRI facilitates serotonergic intrinsic activity [6]

L-type voltage dependent Ca2+ channel (VDCC) plays a significant role in intrinsic activity of raphe serotonergic neurons. Long-term administration of an SSRI decreases GABAB receptor signaling in raphe serotonergic neurons and increased L-type VDCC-mediated current and serotonergic intrinsic activity.

Cortico-striatal dysfunctions in a novel mouse model for obsessive-compulsive disorders

Though SSRIs are commonly used therapeutic agents, the percentage of “SSRI-resistant” cases is still high. Especially, for treating obsessive-compulsive disorder (OCD), which requires longer administration and higher dose than treating depression, about 50% of patients did not respond to SSRI therapy. Clinical studies suggest that treatment efficacy of SSRIs varies between the types of OCD symptoms (e.g. washing, repeating rituals…).
While OCD was classified as an anxiety disorder, dysfunction of decision making is also accepted as a main symptom of OCD. We have developed a novel experimental model of OCD, which shows OCD-related neurological and behavioral abnormalities, including dysfunction of decision making. By using this model, we have addressed the following questions: “What is the action mechanisms of SSRI?”, “What could be novel therapeutic targets for SSRI-resistant OCD?”, “What is the neurological mechanisms for compulsive decision making?”

  • Repeated stimulation of dopamine D2 receptors induced both SSRI-responsive and SSRI-resistant OCD-like abnormalities [9]

Mice received repeated injection of a dopamine D2 receptor agonist showed neurological and behavioral abnormalities reflecting those reported in OCD patients. Long-term administration of an SSRI inhibited a part of these abnormalities (e.g. perseverative behavior), while the same treatment did not show any effect on other OCD-like abnormalities (e.g. behavior repetition). We also reported that an adenosine A2A receptor antagonist, istradefylline (clinically used as an anti-parkinsonian drug), can improve both SSRI-responsive and SSRI-resistant OCD-like behaviors.

  • Abnormal D2 receptor signaling in the central striatum regulates compulsive behavioral repetition [14]

Acute and repeated stimulation of D2 receptors induce different behaviors: sedation and compulsive behavioral repetition, respectively. This suggests that D2 receptor signaling is changed after repeated stimulation. After repeated injection of a D2 receptor agonist, ex vivo stimulation of D2 receptors induce excitatory synaptic facilitation in indirect pathway projecting neurons of the central striatum. D2 receptor-β arrestin signaling was necessary for induction of such synaptic facilitation (ex vivo) and behavior repetition (in vivo). We also found that repeated stimulation of D2 receptors upregulates expression of NADPH oxidase 1 in the central striatum and NADPH oxidase 1-derived reactive oxygen species plays a key role for facilitation of D2 receptor-β arrestin signaling in the striatal neurons.

Neuronal mechanisms for experience-memory relationship regulating compulsive decision making

Compulsive decision making is a common problem in several psychiatric disorders, such as OCD, addiction and eating disorder. Even in healthy persons, compulsive thoughts/behaviors (e.g. “I know that this is unnecessary, but I usually do”, “I don’t want to do this, but I have to do”) can be appeared. However, how such compulsive thoughts/behaviors is acquired remains to be elucidated.
To address this issue, we are now studying neuronal mechanisms underlying compulsive thoughts/behaviors by utilizing a “workaholic”-like behavior as a model of compulsive decision making. Workaholic is defined as compulsive “I have to work” thinking as well as heavy work. Such compulsivity is gradually formed by everyday working experience; however whether one becomes workaholic or not seems to be defined not only “What is experienced” but also “what is learned/memorized from the experience”. We hypothesize that the memory of working experience is stored in the prefrontal cortex as long-term memory and regulates the mode of decision making. We are now testing this hypothesis by behavioral and electrophysiological analysis.

Publications

  1. Nagayasu, K., Kitaichi, M., Nishitani, N., Asaoka, N., Shirakawa, H., Nakagawa, T., & Kaneko, S. (2013).
    Chronic effects of antidepressants on serotonin release in rat raphe slice cultures: high potency of milnacipran in the augmentation of serotonin release. The international journal of neuropsychopharmacology, 16(10), 2295-306. [PubMed:23920436] [WorldCat] [DOI]
  2. Nishitani, N., Nagayasu, K., Asaoka, N., Yamashiro, M., Shirakawa, H., Nakagawa, T., & Kaneko, S. (2014).
    Raphe AMPA receptors and nicotinic acetylcholine receptors mediate ketamine-induced serotonin release in the rat prefrontal cortex. The international journal of neuropsychopharmacology, 17(8), 1321-6. [PubMed:24852262] [WorldCat] [DOI]
  3. Asaoka, N., Nagayasu, K., Nishitani, N., Yamashiro, M., Shirakawa, H., Nakagawa, T., & Kaneko, S. (2015).
    Inhibition of histone deacetylases enhances the function of serotoninergic neurons in organotypic raphe slice cultures. Neuroscience letters, 593, 72-7. [PubMed:25796177] [WorldCat] [DOI]
  4. Asaoka, N., Nagayasu, K., Nishitani, N., Yamashiro, M., Shirakawa, H., Nakagawa, T., & Kaneko, S. (2015).
    Olanzapine augments the effect of selective serotonin reuptake inhibitors by suppressing GABAergic inhibition via antagonism of 5-HT₆ receptors in the dorsal raphe nucleus. Neuropharmacology, 95, 261-8. [PubMed:25863120] [WorldCat] [DOI]
  5. Asaoka, N., Kawai, H., Nishitani, N., Kinoshita, H., Shibui, N., Nagayasu, K., Shirakawa, H., & Kaneko, S. (2016).
    A new designer drug 5F-ADB activates midbrain dopaminergic neurons but not serotonergic neurons. The Journal of toxicological sciences, 41(6), 813-816. [PubMed:27853110] [WorldCat] [DOI]
  6. Nozomi Asaoka, Naoya Nishitani, Haruko Kinoshita, Hiroyuki Kawai, Norihiro Shibui, Kazuki Nagayasu, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko
    Chronic antidepressant potentiates spontaneous activity of dorsal raphe serotonergic neurons by decreasing GABABreceptor-mediated inhibition of L-type calcium channels. Scientific reports: 2017, 7(1), 13609 [PubMed:29051549] [PMC] [WorldCat] [DOI]
  7. Kinoshita, H., Nishitani, N., Nagai, Y., Andoh, C., Asaoka, N., Kawai, H., Shibui, N., Nagayasu, K., Shirakawa, H., Nakagawa, T., & Kaneko, S. (2018).
    Ketamine-Induced Prefrontal Serotonin Release Is Mediated by Cholinergic Neurons in the Pedunculopontine Tegmental Nucleus. The international journal of neuropsychopharmacology, 21(3), 305-310. [PubMed:29370396] [PMC] [WorldCat] [DOI]
  8. Hiroyuki Kawai, Nozomi Asaoka, Takahito Miyake, Kazuki Nagayasu, Takayuki Nakagawa, Hisashi Shirakawa, Shuji Kaneko
    Neurotropin inhibits neuronal activity through potentiation of sustained K vcurrents in primary cultured DRG neurons.Journal of pharmacological sciences: 2018, 137(3), 313-316.[PubMed:29907377] [WorldCat] [DOI]
  9. Nozomi Asaoka, Naoya Nishitani, Haruko Kinoshita, Yuma Nagai, Hikari Hatakama, Kazuki Nagayasu, Hisashi Shirakawa, Takayuki Nakagawa, Shuji Kaneko
    An Adenosine A2A Receptor Antagonist Improves Multiple Symptoms of Repeated Quinpirole-Induced Psychosis.eNeuro: 2019, 6(1).[PubMed:30834304 ] [PMC] [WorldCat] [DOI]
  10. Wen, X., Iwata, K., Ikuta, K., Zhang, X., Zhu, K., Ibi, M., Matsumoto, M., Asaoka, N., Liu, J., Katsuyama, M., & Yabe-Nishimura, C. (2019).
    NOX1/NADPH oxidase regulates the expression of multidrug resistance-associated protein 1 and maintains intracellular glutathione levels. The FEBS journal, 286(4), 678-687. [PubMed:30653821] [WorldCat] [DOI]
  11. Nishitani, N., Nagayasu, K., Asaoka, N., Yamashiro, M., Andoh, C., Nagai, Y., Kinoshita, H., Kawai, H., Shibui, N., Liu, B., Hewinson, J., Shirakawa, H., Nakagawa, T., Hashimoto, H., Kasparov, S., & Kaneko, S. (2019).
    Manipulation of dorsal raphe serotonergic neurons modulates active coping to inescapable stress and anxiety-related behaviors in mice and rats. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 44(4), 721-732. [PubMed:30377380] [PMC] [WorldCat] [DOI]
  12. Liu, J., Iwata, K., Zhu, K., Matsumoto, M., Matsumoto, K., Asaoka, N., Zhang, X., Ibi, M., Katsuyama, M., Tsutsui, M., Kato, S., & Yabe-Nishimura, C. (2020).
    NOX1/NADPH oxidase in bone marrow-derived cells modulates intestinal barrier function. Free radical biology & medicine, 147, 90-101. [PubMed:31838229] [WorldCat] [DOI]
  13. Katsuyama, M., Kimura, E., Ibi, M., Iwata, K., Matsumoto, M., Asaoka, N., & Yabe-Nishimura, C. (2021).
    Clioquinol inhibits dopamine-β-hydroxylase secretion and noradrenaline synthesis by affecting the redox status of ATOX1 and copper transport in human neuroblastoma SH-SY5Y cells. Archives of toxicology, 95(1), 135-148. [PubMed:33034664] [WorldCat] [DOI]
  14. Zhang, X., Ibi, M., Haga, R., Iwata, K., Matsumoto, M., Asaoka, N., Liu, J., Katsuyama, M., & Yabe-Nishimura, C. (2021).
    NOX1/NADPH oxidase affects the development of autism-like behaviors in a maternal immune activation model. Biochemical and biophysical research communications, 534, 59-66. [PubMed:33310189] [WorldCat] [DOI]
  15. Nozomi Asaoka, Masakazu Ibi, Hikari Hatakama, Koki Nagaoka, Kazumi Iwata, Misaki Matsumoto, Masato Katsuyama, Shuji Kaneko, Chihiro Yabe-Nishimura
    NOX1/NADPH Oxidase Promotes Synaptic Facilitation Induced by Repeated D2 Receptor Stimulation: Involvement in Behavioral Repetition. The Journal of neuroscience : the official journal of the Society for Neuroscience: 2021, 41(12), 2780-2794.[PubMed:33563722] [PMC] [WorldCat] [DOI]
  16. Nagaoka, K., Nagashima, T., Asaoka, N., Yamamoto, H., Toda, C., Kayanuma, G., Siswanto, S., Funahashi, Y., Kuroda, K., Kaibuchi, K., Mori, Y., Nagayasu, K., Shirakawa, H., & Kaneko, S. (2021).
    Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonist-induced orofacial dyskinesia. JCI insight, 6(10). [PubMed:33857021] [PMC] [WorldCat] [DOI]
  17. Matsumoto, M., Liu, J., Iwata, K., Ibi, M., Asaoka, N., Zhang, X., Katsuyama, M., Matsuda, M., Nabe, T., Schröder, K., & Yabe-Nishimura, C. (2021).
    NOX1/NADPH oxidase is involved in the LPS-induced exacerbation of collagen-induced arthritis. Journal of pharmacological sciences, 146(2), 88-97. [PubMed:33941325] [WorldCat] [DOI]

Teaching experience

B11a/b Pharmacology lecture and practice

Academic Society

The Japanese Pharmacological Society
The Pharmaceutical Society of Japan
The Japanese Neuroscience Society
The Japanese Society of Neuropsychopharmacology
Society for Neuroscience

Personal Aspects

Hobbies:
Reading (Mystery, SF and fantasy novels), blood donation

Contact address

Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Room 403, Building A, Department of pharmacology, Graduate School of Medicine, Kyoto University
E-mail address: asaoka.nozomi.3s [at] kyoto-u.ac.jp

External Links

Retrieved from "http://glutamate.med.kyoto-u.ac.jp/e/index.php?title=Nozomi_Asaoka&oldid=156"