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Article ; Online: Reduced serotonergic transmission alters sensitivity to cost and reward via 5-HT1A and 5-HT1B receptors in monkeys

Yukiko Hori / Koki Mimura / Yuji Nagai / Yuki Hori / Katsushi Kumata / Ming-Rong Zhang / Tetsuya Suhara / Makoto Higuchi / Takafumi Minamimoto

PLoS Biology, Vol 22, Iss

2024 Volume 1

Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Reduced serotonergic transmission alters sensitivity to cost and reward via 5-HT1A and 5-HT1B receptors in monkeys.

Hori, Yukiko / Mimura, Koki / Nagai, Yuji / Hori, Yuki / Kumata, Katsushi / Zhang, Ming-Rong / Suhara, Tetsuya / Higuchi, Makoto / Minamimoto, Takafumi

PLoS biology

2024 Volume 22, Issue 1, Page(s) e3002445

Abstract: Serotonin (5-HT) deficiency is a core biological pathology underlying depression and other psychiatric disorders whose key symptoms include decreased motivation. However, the exact role of 5-HT in motivation remains controversial and elusive. Here, we ... ...

Abstract	Serotonin (5-HT) deficiency is a core biological pathology underlying depression and other psychiatric disorders whose key symptoms include decreased motivation. However, the exact role of 5-HT in motivation remains controversial and elusive. Here, we pharmacologically manipulated the 5-HT system in macaque monkeys and quantified the effects on motivation for goal-directed actions in terms of incentives and costs. Reversible inhibition of 5-HT synthesis increased errors and reaction times on goal-directed tasks, indicating reduced motivation. Analysis found incentive-dependent and cost-dependent components of this reduction. To identify the receptor subtypes that mediate cost and incentive, we systemically administered antagonists specific to 4 major 5-HT receptor subtypes: 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4. Positron emission tomography (PET) visualized the unique distribution of each subtype in limbic brain regions and determined the systemic dosage for antagonists that would achieve approximately 30% occupancy. Only blockade of 5-HT1A decreased motivation through changes in both expected cost and incentive; sensitivity to future workload and time delay to reward increased (cost) and reward value decreased (incentive). Blocking the 5-HT1B receptor also reduced motivation through decreased incentive, although it did not affect expected cost. These results suggest that 5-HT deficiency disrupts 2 processes, the subjective valuation of costs and rewards, via 5-HT1A and 5-HT1B receptors, thus leading to reduced motivation.
MeSH term(s)	Brain/metabolism ; Carrier Proteins/metabolism ; Receptor, Serotonin, 5-HT1B ; Serotonin ; Serotonin Antagonists/pharmacology ; Macaca ; Animals
Chemical Substances	Carrier Proteins ; Receptor, Serotonin, 5-HT1B ; Serotonin (333DO1RDJY) ; Serotonin Antagonists
Language	English
Publishing date	2024-01-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2126776-5
ISSN	1545-7885 ; 1544-9173
ISSN (online)	1545-7885
ISSN	1544-9173
DOI	10.1371/journal.pbio.3002445
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Article ; Online: Promotion in the Clearance of Aggregated Aβ In Vivo Using Amyloid Selective Photo-Oxygenation Technology.

Hori, Yukiko / Sohma, Youhei / Kanai, Motomu / Tomita, Taisuke

Neuroscience insights

2022 Volume 17, Page(s) 26331055221126179

Abstract: Alzheimer's disease (AD) is characterized by the aggregation and deposition of 2 amyloid proteins: amyloid β peptide (Aβ) and tau protein. Immunotherapies using anti-Aβ antibodies to promote the clearance of aggregated Aβ have recently been highlighted ... ...

Abstract	Alzheimer's disease (AD) is characterized by the aggregation and deposition of 2 amyloid proteins: amyloid β peptide (Aβ) and tau protein. Immunotherapies using anti-Aβ antibodies to promote the clearance of aggregated Aβ have recently been highlighted as a promising disease-modifying approach against AD. However, immunotherapy has still some problems, such as low efficiency of delivery into the brain and high costs. We have developed the "amyloid selective photo-oxygenation technology" as a comparable to immunotherapy for amyloids. The photo-oxygenation can artificially attach the oxygen atoms to specific amino acids in amyloid proteins using photocatalyst and light irradiation. We revealed that in vivo photo-oxygenation for living AD model mice reduced the aggregated Aβ in the brain. Moreover, we also showed that microglia were responsible for this promoted clearance of photo-oxygenated Aβ from the brain. These results indicated that our photo-oxygenation technology has the potential as a disease-modifying therapy against AD to promote the degradation of amyloids, resulting in being comparable to immunotherapy. Here, we introduce our technology and its effects in vivo that we showed previously in Ozawa et al.,
Language	English
Publishing date	2022-09-28
Publishing country	United States
Document type	Journal Article ; Comment
ISSN	2633-1055
ISSN (online)	2633-1055
DOI	10.1177/26331055221126179
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Article ; Online: Association between organizational justice and serious psychological distress among hospital nursing staff during the COVID-19 pandemic: A cross-sectional study.

Ikeda, Satoshi / Masumitsu, Makoto / Aomoto, Satomi / Yamashita, Masanori / Kakeda, Haruka / Nagatomo, Eri / Kiyota, Yukiko / Matsueda, Michiko / Hori, Hikaru

Japan journal of nursing science : JJNS

2024 , Page(s) e12595

Abstract: Aim: Amidst the COVID-19 pandemic, the association between organizational justice and psychological distress among hospital nursing staff is underexplored. Thus, this cross-sectional study, conducted in Fukuoka Prefecture, Japan, examined the ... ...

Abstract	Aim: Amidst the COVID-19 pandemic, the association between organizational justice and psychological distress among hospital nursing staff is underexplored. Thus, this cross-sectional study, conducted in Fukuoka Prefecture, Japan, examined the relationship between organizational justice and serious psychological distress (SPD) among hospital nursing staff during COVID-19. Methods: The study surveyed 783 hospital nursing staff using the Organizational Justice Questionnaire and Effort-Reward Imbalance Questionnaire. The Kessler K6 scale was used to measure SPD. Sociodemographic and occupational characteristics were controlled for as potential confounders. Results: The prevalence of SPD was 14.4%, with a mean K6 score of 6.5. Moderate procedural justice (odds ratio [OR] = 2.38, 95% confidence interval [CI] = 1.14-4.94, p = .021) and low distributive justice (effort-reward imbalance) (OR = 3.66, 95% CI = 2.01-6.67, p < .001) were associated with SPD, even after adjustment for confounders. Interactional justice showed significance only in the crude model. Effort-reward imbalance had the strongest association with SPD. Conclusions: The findings showed that moderate procedural justice and low distributive justice were associated with SPD, highlighting the need for organizational interventions to address these factors. Imbalances in effort/reward had the greatest impact, highlighting the critical role of distributive justice in mental health. Thus, in the context of a pandemic, extreme procedural justice is not necessarily associated with mental health, and efforts to ensure distributive justice are critical to improving the mental health of hospital nursing staff. Moreover, organizational stressors should be addressed during disruptive conditions such as infectious disease outbreaks.
Language	English
Publishing date	2024-03-08
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2156618-5
ISSN	1742-7924 ; 1742-7932
ISSN (online)	1742-7924
ISSN	1742-7932
DOI	10.1111/jjns.12595
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Article: Photo-Oxygenation: An Innovative New Therapeutic Approach Against Amyloidoses.

Ikeda, Tetsuo / Hori, Yukiko / Sohma, Youhei / Kanai, Motomu / Tomita, Taisuke

Advances in experimental medicine and biology

2022 Volume 1339, Page(s) 415–422

Abstract: Many types of amyloidoses are pathologically characterized by the deposition of amyloid, which is comprised of fibrils formed by abnormally aggregated proteins, in various peripheral tissues and the central nervous system (CNS). Neurodegenerative ... ...

Abstract	Many types of amyloidoses are pathologically characterized by the deposition of amyloid, which is comprised of fibrils formed by abnormally aggregated proteins, in various peripheral tissues and the central nervous system (CNS). Neurodegenerative disorders, such as Alzheimer disease (AD), Parkinson disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), are well-known CNS amyloidoses that are characterized by amyloid deposition both inside and outside of cells. The amyloidogenic proteins of each disease have distinct primary sequences, and they normally function as soluble proteins. However, these proteins all aggregate and form amyloid with a common intermolecular tertiary structure, namely, a cross-β-sheet structure, finally leading to the onset of each disease. Therefore, inhibition of the aggregation of amyloid proteins or efficient clearance of the already formed amyloids are thought to be promising therapeutic strategies against amyloidoses.
MeSH term(s)	Alzheimer Disease ; Amyloid ; Amyloidosis/therapy ; Frontotemporal Dementia ; Humans ; Parkinson Disease
Chemical Substances	Amyloid
Language	English
Publishing date	2022-01-13
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-030-78787-5_52
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Article ; Online: Soluble form of the APP fragment, sAPPβ, positively regulates tau secretion.

Sato, Haruaki / Kasuga, Kensaku / Isoo, Noriko / Hayashi, Toshihiro / Ikeuchi, Takeshi / Hori, Yukiko / Tomita, Taisuke

Neuroscience research

2023 Volume 193, Page(s) 63–70

Abstract: Extracellular tau has been highlighted in the pathogenesis of Alzheimer disease (AD), which is the most common neurodegenerative disease. Pathological analyses as well as model animal studies suggest that amyloid-β peptide (Aβ) deposition facilitates the ...

Abstract	Extracellular tau has been highlighted in the pathogenesis of Alzheimer disease (AD), which is the most common neurodegenerative disease. Pathological analyses as well as model animal studies suggest that amyloid-β peptide (Aβ) deposition facilitates the spreading of tau aggregation pathology via extracellular tau. However, the precise mechanism of tau secretion remains unknown. Here, we show that the overexpression of amyloid precursor protein (APP) enhances the secretion of tau phosphorylated at threonine 181 in mouse neuroblastoma Neuro2a cells. Moreover, we found that soluble amyloid precursor protein β (sAPPβ), which is generated by β-site APP cleaving enzyme 1 (BACE1), mediates tau secretion. Our results demonstrate that BACE1-mediated cleavage of APP plays pathological roles in AD pathogenesis by not only Aβ production, but by the spreading of tau aggregation pathology via sAPPβ in AD patients.
MeSH term(s)	Animals ; Mice ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Amyloid beta-Protein Precursor/metabolism ; Amyloid Precursor Protein Secretases/metabolism ; Aspartic Acid Endopeptidases/metabolism ; Neurodegenerative Diseases ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Amyloid Precursor Protein Secretases (EC 3.4.-) ; Aspartic Acid Endopeptidases (EC 3.4.23.-) ; tau Proteins ; Mapt protein, mouse ; APP protein, mouse
Language	English
Publishing date	2023-03-24
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	605842-5
ISSN	1872-8111 ; 0168-0102 ; 0921-8696
ISSN (online)	1872-8111
ISSN	0168-0102 ; 0921-8696
DOI	10.1016/j.neures.2023.03.002
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Article ; Online: Attenuation of α-synuclein aggregation by catalytic photo-oxygenation.

Iwai, Atsushi / Nakamura, Reito / Tomizawa, Ikumi / Mitsunuma, Harunobu / Hori, Yukiko / Tomita, Taisuke / Sohma, Youhei / Kanai, Motomu

Chemical communications (Cambridge, England)

2023 Volume 59, Issue 38, Page(s) 5745–5748

Abstract: We developed catalyst 11 to promote selective photo-oxygenation of α-synuclein amyloid and attenuate its aggregation. Catalyst 11 effectively oxygenated both small and large aggregates. The oxygenated α-synuclein exhibited lower seeding activity than ... ...

Abstract	We developed catalyst 11 to promote selective photo-oxygenation of α-synuclein amyloid and attenuate its aggregation. Catalyst 11 effectively oxygenated both small and large aggregates. The oxygenated α-synuclein exhibited lower seeding activity than intact α-synuclein. This study corroborates the feasibility of catalytic photo-oxygenation as an anti-synucleinopathy strategy.
MeSH term(s)	alpha-Synuclein ; Amyloid
Chemical Substances	alpha-Synuclein ; Amyloid
Language	English
Publishing date	2023-05-09
Publishing country	England
Document type	Journal Article
ZDB-ID	1472881-3
ISSN	1364-548X ; 1359-7345 ; 0009-241X
ISSN (online)	1364-548X
ISSN	1359-7345 ; 0009-241X
DOI	10.1039/d3cc00665d
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Article: Photo-Oxygenation as a New Therapeutic Strategy for Neurodegenerative Proteinopathies by Enhancing the Clearance of Amyloid Proteins.

Tomizawa, Ikumi / Nakagawa, Hanako / Sohma, Youhei / Kanai, Motomu / Hori, Yukiko / Tomita, Taisuke

Frontiers in aging neuroscience

2022 Volume 14, Page(s) 945017

Abstract: Alzheimer disease (AD) is associated with the aggregation of two amyloid proteins: tau and amyloid-β (Aβ). The results of immunotherapies have shown that enhancing the clearance and suppressing the aggregation of these two proteins are effective ... ...

Abstract	Alzheimer disease (AD) is associated with the aggregation of two amyloid proteins: tau and amyloid-β (Aβ). The results of immunotherapies have shown that enhancing the clearance and suppressing the aggregation of these two proteins are effective therapeutic strategies for AD. We have developed photocatalysts that attach oxygen atoms to Aβ and tau aggregates
Language	English
Publishing date	2022-06-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2022.945017
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Article ; Online: Acute Cholesterol-Lowering Effect of Exendin-4 in Ldlr

Hori, Mika / Hasegawa, Yukiko / Hayashi, Yoshitaka / Nakagami, Tomoko / Harada-Shiba, Mariko

Journal of atherosclerosis and thrombosis

2022 Volume 30, Issue 1, Page(s) 74–86

Abstract: Aims: We previously reported that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduced serum low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus receiving statins, which increased LDL receptor (LDLR) ... ...

Abstract	Aims: We previously reported that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduced serum low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus receiving statins, which increased LDL receptor (LDLR) expression. Nevertheless, it remains unclear how much LDLR expression contributes to the LDL-C-lowering effect of GLP-1RAs. We examined the effect of a GLP-1RA, namely, exendin-4, on serum LDL-C levels and its mechanism in Ldlr Methods: Ten-week-old Ldlr Results: Exendin-4 treatment significantly decreased serum very-low-density lipoprotein cholesterol (VLDL-C) and LDL-C levels and mature hepatic SREBP2 levels and increased hepatic Insig1/2 mRNA expression in both mouse strains. In Ldlr Conclusions: Our findings demonstrate that exendin-4 treatment decreased serum VLDL-C and LDL-C levels in a manner that was independent of LDLR. Exendin-4 treatment might decrease serum cholesterol levels by lowering hepatic SREBP2 levels and cholesterol absorption in Ldlr
MeSH term(s)	Mice ; Animals ; Exenatide ; Cholesterol, LDL ; Diabetes Mellitus, Type 2/drug therapy ; Mice, Inbred C57BL ; Cholesterol ; Receptors, LDL/genetics ; Receptors, LDL/metabolism ; RNA, Messenger
Chemical Substances	Exenatide (9P1872D4OL) ; Cholesterol, LDL ; Cholesterol (97C5T2UQ7J) ; Receptors, LDL ; RNA, Messenger
Language	English
Publishing date	2022-03-19
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2011474-6
ISSN	1880-3873 ; 1340-3478
ISSN (online)	1880-3873
ISSN	1340-3478
DOI	10.5551/jat.60921
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Article ; Online: Stable Neural Population Dynamics in the Regression Subspace for Continuous and Categorical Task Parameters in Monkeys.

Chen, He / Kunimatsu, Jun / Oya, Tomomichi / Imaizumi, Yuri / Hori, Yukiko / Matsumoto, Masayuki / Minamimoto, Takafumi / Naya, Yuji / Yamada, Hiroshi

eNeuro

2023 Volume 10, Issue 7

Abstract: Neural population dynamics provide a key computational framework for understanding information processing in the sensory, cognitive, and motor functions of the brain. They systematically depict complex neural population activity, dominated by strong ... ...

Abstract	Neural population dynamics provide a key computational framework for understanding information processing in the sensory, cognitive, and motor functions of the brain. They systematically depict complex neural population activity, dominated by strong temporal dynamics as trajectory geometry in a low-dimensional neural space. However, neural population dynamics are poorly related to the conventional analytical framework of single-neuron activity, the rate-coding regime that analyzes firing rate modulations using task parameters. To link the rate-coding and dynamic models, we developed a variant of state-space analysis in the regression subspace, which describes the temporal structures of neural modulations using continuous and categorical task parameters. In macaque monkeys, using two neural population datasets containing either of two standard task parameters, continuous and categorical, we revealed that neural modulation structures are reliably captured by these task parameters in the regression subspace as trajectory geometry in a lower dimension. Furthermore, we combined the classical optimal-stimulus response analysis (usually used in rate-coding analysis) with the dynamic model and found that the most prominent modulation dynamics in the lower dimension were derived from these optimal responses. Using those analyses, we successfully extracted geometries for both task parameters that formed a straight geometry, suggesting that their functional relevance is characterized as a unidimensional feature in their neural modulation dynamics. Collectively, our approach bridges neural modulation in the rate-coding model and the dynamic system, and provides researchers with a significant advantage in exploring the temporal structure of neural modulations for pre-existing datasets.
MeSH term(s)	Animals ; Neurons/physiology ; Brain ; Macaca ; Cognition ; Population Dynamics
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2800598-3
ISSN	2373-2822 ; 2373-2822
ISSN (online)	2373-2822
ISSN	2373-2822
DOI	10.1523/ENEURO.0016-23.2023
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