title: Effects of chronic administration with nilvadipine against immunohistochemical changes related to aging in the mouse hippocampus.
abstract: We investigated the effect of Ca2+ antagonist nilvadipine on age-related immunohistochemical alterations in ubiquitin and S100beta protein of the hippocampal CA1 sector in mice using 8-, 18-, 40-, and 59-week-old mice. No significant changes in the number of neuronal cells were observed in the hippocampal CA1 sector up to 59 weeks after birth. The administration of nilvadipine did not affect the number of the hippocampal CA1 cells of 40-week-old mice. Age-dependent increases in ubiquitin immunoreactivity were observed in the hippocampal CA1 neurons up to 59 weeks after birth. The administration of nilvadipine prevented dose-dependently the increases in the number of ubiquitin-immunoreactive neurons in the hippocampal CA1 sector of 40-week-old mice. S100,beta immunoreactivity was unchanged in the hippocampal CA1 sector up to 40 weeks after birth. In 59-week-old mice, the level of staining of S100beta-immunoreactive cells increased significantly in the hippocampal CA1 sector. The administration of nilvadipine decreased dose-dependently the number of S 100beta-immunoreactive cells in the hippocampal CA1 sector of 40-week-old mice. The present study demonstrates that age-related increases in ubiquitin system may play a pivotal role in protecting neuronal cell damage during aging. In contrast, our results suggest that expression of S 100beta protein in the hippocampal CA1 sector may play an exacerbating factor in some neuronal cells damaged by aging. Our results also demonstrate that nilvadipine, a dihydropyridine-type calcium channel blocker, can prevent dose-dependently the increases in the ubiquitin immunoreactive neurons and decrease the number of S100beta immunoreactive cells in the hippocampal CA1 neurons of aged mice. These results suggest that nilvadipine may offer a new approach for the treatment of neuronal dysfunction in aged humans.
authors.affiliation: Department of Drug Metabolism and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Himeda
authors.forename: Shiori
authors.initials: S
authors.lastname: Kanbara
authors.forename: Chie
authors.initials: C
authors.lastname: Oki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kato
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Araki
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008813:Mice, Inbred ICR; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000187:drug effects / Q000378:metabolism; D025801:Ubiquitin / Q000187:drug effects / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D025801:Ubiquitin; C035100:nilvadipine; D009543:Nifedipine