Changing trends in health orientation among older adults: A scoping review.

Older people's health condition is not uniform, and the components of their health are interrelated. Concepts regarding the health of older people have emerged and changed over time. However, the transition of concepts and influencing factors are not well examined through research. We have conducted a scoping review of the changes over time in the concept of health for older people and the factors influencing these changes. The public websites of international organizations and academic societies related to older people's health and research paper database were searched, and the extracted data were summarized in a chronological table. Consequently, this study revealed changing trends in health orientation after health had been defined by WHO, namely, successful aging, productive aging, active aging, and healthy aging, and their components, not the concept of health. The emergence and changes of health orientation among older people may have accompanied proposals and measures of international organizations and academic societies developed in response to changes in the demographic structure, and changes in how society perceives and supports older people. With the changing eras that bring about advances in health technology, prolongation of life expectancy, and changes in lifestyles, the needs of older people, society's perceptions of aging and older people, and how to support them will also change. Our findings may provide a valuable basis for understanding aging and older people, reconsidering their health orientation based on the health issues of older people and their significance, and formulating policies for older people in the future. Geriatr Gerontol Int 2024; 24: 5-17.

Loss of GluN2D subunit results in social recognition deficit, social stress, 5-HT2C receptor dysfunction, and anhedonia in mice.

The N-methyl-d-aspartate (NMDA) receptor channel is involved in various physiological functions, including learning and memory. The GluN2D subunit of the NMDA receptor has low expression in the mature brain, and its role is not fully understood. In the present study, the effects of GluN2D subunit deficiency on emotional and cognitive function were investigated in GluN2D knockout (KO) mice. We found a reduction of motility (i.e., a depressive-like state) in the tail suspension test and a reduction of sucrose preference (i.e., an anhedonic state) in GluN2D KO mice that were group-housed with littermates. Despite apparently normal olfactory function and social interaction, GluN2D KO mice exhibited a decrease in preference for social novelty, suggesting a deficit in social recognition or memory. Golgi-Cox staining revealed a reduction of the complexity of dendritic trees in the accessory olfactory bulb in GluN2D KO mice, suggesting a deficit in pheromone processing pathway activation, which modulates social recognition. The deficit in social recognition may result in social stress in GluN2D KO mice. Isolation housing is a procedure that has been shown to reduce stress in mice. Interestingly, 3-week isolation and treatment with agomelatine or the 5-hydroxytryptamine-2C (5-HT2C) receptor antagonist SB242084 reversed the anhedonic-like state in GluN2D KO mice. In contrast, treatment with the 5-HT2C receptor agonist CP809101 induced depressive- and anhedonic-like states in isolated GluN2D KO mice. These results suggest that social stress that is caused by a deficit in social recognition desensitizes 5-HT2c receptors, followed by an anhedonic- and depressive-like state, in GluN2D KO mice. The GluN2D subunit of the NMDA receptor appears to be important for the recognition of individuals and development of normal emotionality in mice. 5-HT2C receptor antagonism may be a therapeutic target for treating social stress-induced anhedonia. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

Design and Synthesis of a 4-Nitrobromobenzene Derivative Bearing an Ethylene Glycol Tetraacetic Acid Unit for a New Generation of Caged Calcium Compounds with Two-Photon Absorption Properties in the Near-IR Region and Their Application in Vivo.

Among biologically active compounds, calcium ions (Ca2+) are one of the most important species in cell physiological functions. Development of new calcium chelators with two-photon absorption (TPA) properties is a state-of-the-art challenge for chemists. In this study, we report the first and efficient synthesis of 5-bromo-2-nitrobenzyl-substituted ethylene glycol tetraacetic acid (EGTA) as a platform for a new generation of calcium chelators with TPA properties in the near-infrared region. New calcium chelators with high TPA properties, that is, a two-photon (TP) fragmentation efficiency of δu = 20.7 GM at 740 nm for 2-(4-nitrophenyl)benzofuran (NPBF)-substituted EGTA (NPBF-EGTA, K d = 272 nM) and δu = 7.8 GM at 800 nm for 4-amino-4'-nitro-1,1'-biphenyl (BP)-substituted EGTA (BP-EGTA, K d = 440 nM) derivatives, were synthesized using Suzuki-Miyaura coupling reactions of the bromide with benzofuran-2-boronic acid and 4-(dimethylamino)phenyl boronic acid, respectively. The corresponding acetoxymethyl (AM) esters were prepared and successfully applied to the Ca2+-uncaging reaction triggered by TP photolysis in vivo.

Design and synthesis of a new chromophore, 2-(4-nitrophenyl)benzofuran, for two-photon uncaging using near-IR light.

A new chromophore, 2-(4-nitrophenyl)benzofuran (NPBF), was designed for two-photon (TP) uncaging using near-IR light. The TP absorption (TPA) cross-sections of the newly designed NPBF chromophore were determined to be 18 GM at 720 nm and 54 GM at 740 nm in DMSO. The TP uncaging reaction of a caged benzoate with the NPBF chromophore quantitatively produced benzoic acid with an efficiency (δu) of ∼5.0 GM at 740 nm. The TP fragmentation of an EGTA unit was observed with δu = 16 GM. This behavior makes the new chromophore a promising TP photoremovable protecting group for physiological studies.

Two-photon fluorescence lifetime imaging of primed SNARE complexes in presynaptic terminals and ß cells.

It remains unclear how readiness for Ca(2+)-dependent exocytosis depends on varying degrees of SNARE complex assembly. Here we directly investigate the SNARE assembly using two-photon fluorescence lifetime imaging (FLIM) of Förster resonance energy transfer (FRET) between three pairs of neuronal SNAREs in presynaptic boutons and pancreatic ß cells in the islets of Langerhans. These FRET probes functionally rescue their endogenous counterparts, supporting ultrafast exocytosis. We show that trans-SNARE complexes accumulated in the active zone, and estimate the number of complexes associated with each docked vesicle. In contrast, SNAREs were unassembled in resting state, and assembled only shortly prior to insulin exocytosis, which proceeds slowly. We thus demonstrate that distinct states of fusion readiness are associated with SNARE complex formation. Our FRET/FLIM approaches enable optical imaging of fusion readiness in both live and chemically fixed tissues.

Involvement of the N-methyl-D-aspartate receptor GluN2D subunit in phencyclidine-induced motor impairment, gene expression, and increased Fos immunoreactivity.

BACKGROUND: Noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists evoke a behavioral and neurobiological syndrome in experimental animals. We previously reported that phencyclidine (PCP), an NMDA receptor antagonist, increased locomotor activity in wildtype (WT) mice but not GluN2D subunit knockout mice. Thus, the aim of the present study was to determine whether the GluN2D subunit is involved in PCP-induced motor impairment. RESULTS: PCP or UBP141 (a GluN2D antagonist) induced potent motor impairment in WT mice but not GluN2D KO mice. By contrast, CIQ, a GluN2C/2D potentiator, induced severe motor impairment in GluN2D KO mice but not WT mice, suggesting that the GluN2D subunit plays an essential role in the effects of PCP and UBP141, and an appropriate balance between GluN2C and GluN2D subunits might be needed for appropriate motor performance. The level of the GluN2D subunit in the mature mouse brain is very low and restricted. GluN2D subunits exist in brainstem structures, the globus pallidus, thalamus, and subthalamic nucleus. We found that the expression of the c-fos gene increased the most among PCP-dependent differentially expressed genes between WT and GluN2D KO mice, and the number of Fos-positive cells increased after PCP administration in the basal ganglia motor circuit in WT mice but not GluN2D KO mice. CONCLUSION: These results suggest that the GluN2D subunit within the motor circuitry is a key subunit for PCP-induced motor impairment, which requires an intricate balance between GluN2C- and GluN2D-mediated excitatory outputs.