Histamine H 3 receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization during resting state: an exploratory cortex-wide imaging study in mice.

Autor: Kaita S; Endowed Department of Cognitive Function and Pathology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Morishita Y; Endowed Department of Cognitive Function and Pathology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan., Kobayashi K; Section of Viral Vector Development, Center for Genetic Analysis of Behavior, National Institute for Physiological Sciences, Okazaki, 444-8585, Japan., Nomura H; Endowed Department of Cognitive Function and Pathology, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Japan. hnomura@med.nagoya-cu.ac.jp.
Jazyk: angličtina
Zdroj: Molecular brain [Mol Brain] 2024 Nov 27; Vol. 17 (1), pp. 88. Date of Electronic Publication: 2024 Nov 27.
DOI: 10.1186/s13041-024-01165-8
Abstrakt: The histaminergic system plays a key role in modulating learning and memory, wakefulness, and energy balance. Histamine H 3 receptors constitutively inhibit the synthesis and release of histamine and other neurotransmitters. Therefore, H 3 receptor inverse agonists/antagonists increase the synthesis and release of these neurotransmitters, enhancing cognitive functions, including memory consolidation and retrieval. Spontaneous neural activity across the cerebral cortex is essential for cognitive function, including memory consolidation. Abnormal spontaneous activity has, in fact, been associated with cognitive dysfunctions and psychiatric disorders. Given the cognitive improvement achieved with the use of H 3 receptor inverse agonists/antagonists, we examined the effects of two inverse agonists/antagonists - thioperamide and pitolisant - on spontaneous cortical activity, using in vivo wide-field Ca 2+ imaging. Changes in cortical activity, across multiple cortical regions and in inter-regional connectivity, from pre- to post-administration were evaluated using a linear support vector machine decoder. Thioperamide and pitolisant both modified the amplitude distribution of calcium events across multiple cortical regions, including a reduction in the frequency of low-amplitude calcium events in the somatosensory cortex. Graph theory analysis revealed increases in centrality measures in the somatosensory cortex with the use of both thioperamide and pitolisant, indicative of their importance in the organization of cortical networks. These findings indicate that H 3 receptor inverse agonists/antagonists influence intra-regional cortical activity and inter-regional synchronization of activity in the cerebral cortex during the resting state.
Competing Interests: Declarations. Ethics approval and consent to participate: All animal experiments were approved by the Institutional Animal Care and Use Committee of Nagoya City University (approval number: 22 − 018). The study method adhered to the Nagoya City University Guidelines for the Care and Use of Laboratory Animals and complied with relevant national guidelines: Guidelines for Proper Conduct of Animal Experiments (Science Council of Japan), Fundamental Guidelines for Proper Conduct of Animal Experiments and Related Activities in Academic Research Institutions (Ministry of Education, Culture, Sports, Science, and Technology, Notice No. 71 of 2006), and Standards for Breeding and Housing of and Pain Alleviation for Experimental Animals (Ministry of the Environment, Notice No. 88 of 2006). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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