RESUMEN
BACKGROUND: The Newborn Behavioral Observations (NBO) system is an infant-focused, family-centered, relationship-based tool designed to help parents become aware of their baby's abilities and to promote a positive parent-child relationship from the very beginning of birth. AIMS: The aim of this scoping review was to provide an overview of the key characteristics of the research and evidence accumulated over the past 17 years on the early NBO intervention for infants and their parents to identify the existing research gaps and to inform the future direction of research on the NBO System. STUDY DESIGN: A scoping review guided by Arksey and O'Malley's methodological framework and the PRISMA-ScR Checklist was conducted. This review used six databases (PubMed, CINAHL, MEDLINE, Google Scholar, Ichushi-Web, and CiNii) and was limited to English and Japanese language articles from January 2006, when the NBO was developed, to September 2022. Reference lists were also hand-searched to further identify relevant articles from the NBO site. RESULTS: A total of 29 articles were selected. Through the analysis of included articles, four overarching themes were identified: (1) usage pattern of the NBO; (2) participants, setting, duration, and frequency of the NBO intervention; (3) outcome measures and effects of the NBO intervention; and (4) findings from a qualitative perspective. The review suggested that early NBO intervention had a positive impact on maternal mental health and sensitivity to the infant, confidence and knowledge of practitioners, and infant development. CONCLUSIONS: This scoping review shows that the early NBO intervention has been implemented in a variety of cultures and settings and by professionals of various disciplines. However, research to evaluate the long-term effects of this intervention on a wider range of subjects is needed.
Asunto(s)
Técnicas de Observación Conductual , Padres , Humanos , Recién Nacido , Desarrollo Infantil , Salud Mental , Relaciones Padres-Hijo , Padres/psicologíaRESUMEN
One of the most important pathological features of Alzheimer's disease (AD) is extracellular senile plaques, whose major component is amyloid-beta peptides (Abeta). Abeta binds to the extracellular domain of p75NTR (p75 neurotrophin receptor) and induces neuronal cell death. We investigated the molecular mechanism of Abeta-induced neurotoxicity in detail from the standpoint of interaction between p75NTR and its recently identified relative, PLAIDD (p75-like apoptosis-inducing death domain). Using F11 neuronal hybrid cells, we demonstrate that there are two distinct pathways for Abeta-induced toxicity mediated by p75NTR. One pathway that has been previously elucidated, is mediated by p75NTR, Go, JNK, NADPH oxidase and caspase3-related caspases. We found that PLAIDD and Gi proteins, heterotrimeric G proteins, are involved in the alternative Abeta-induced neurotoxicity mediated by p75NTR. The alternative pathway triggered by Abeta is thus mediated by p75NTR, PLAIDD, Gi, JNK, NADPH oxidase and caspase3-related caspases. In addition, we found that HN, ADNF, IGF-I, or bFGF inhibits both pathways of Abeta-induced neurotoxicity mediated by p75NTR.
Asunto(s)
Péptidos beta-Amiloides/farmacología , Proteínas Portadoras/metabolismo , Proteínas de la Membrana/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fragmentos de Péptidos/farmacología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Enfermedad de Alzheimer/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis , Proteínas Portadoras/genética , Caspasa 3 , Caspasas/metabolismo , Muerte Celular/efectos de los fármacos , Muerte Celular/genética , Línea Celular , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/antagonistas & inhibidores , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/metabolismo , Células Híbridas , Péptidos y Proteínas de Señalización Intracelular , Proteínas Quinasas JNK Activadas por Mitógenos , Proteínas de la Membrana/genética , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Mutagénesis Sitio-Dirigida , NADPH Oxidasas/metabolismo , Neuronas/citología , Toxina del Pertussis/farmacología , Proteínas/farmacología , Ratas , Receptor de Factor de Crecimiento Nervioso , Receptores de Factor de Crecimiento Nervioso/genética , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , TransfecciónRESUMEN
Presenilin (PS)1 and its mutants, which consist of the N-terminal and C-terminal fragments, cause certain familial forms of Alzheimer's disease (FAD). Our earlier studies found that FAD-linked M146L-PS1 causes neuronal cell death through nitrogen oxide synthase (NOS) and that FAD-linked N141I-PS2, another member of the PS family, causes neuronal cell death through NADPH oxidase. In this study, we examined 27 different FAD-linked mutants of PS1, and found that PS1 mutants with mutations in the N-terminal fragment caused NOS inhibitor (NOSI)-sensitive neuronal cell death; in contrast, the PS1 mutants with mutations in the C-terminal fragment caused NOSI-resistant neuronal cell death. The former toxicity was resistant to the specific NADPH oxidase inhibitor apocynin and was inhibited by Humanin (HN), a newly identified neuroprotective factor against Alzheimer's disease (AD)-relevant insults, but not by insulin-like growth factor-I (IGF-I). In contrast, the latter toxicity was sensitive to apocynin and inhibited by both IGF-I and HN. This study indicates for the first time that N- and C-terminal fragment PS1 mutants can generate distinct neurotoxic signals, which will provide an important clue to the understanding of the entire array of neurotoxic signals generated by FAD-causative mutations of PS1.
Asunto(s)
Enfermedad de Alzheimer/genética , Muerte Celular/genética , Proteínas de la Membrana/genética , Neuronas/efectos de los fármacos , Acetofenonas/farmacología , Animales , Muerte Celular/efectos de los fármacos , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Immunoblotting , Factor I del Crecimiento Similar a la Insulina/farmacología , Péptidos y Proteínas de Señalización Intracelular , Proteínas de la Membrana/química , Mutación , NADPH Oxidasas/metabolismo , Fármacos Neuroprotectores/farmacología , Neurotoxinas/genética , Neurotoxinas/farmacología , Óxido Nítrico Sintasa/metabolismo , Presenilina-1 , Proteínas/farmacologíaRESUMEN
Neuronal pathology of the brain with Alzheimer's disease (AD) is characterized by numerous depositions of amyloid-beta peptides (Abeta). Abeta binding to the 75-kDa neurotrophin receptor (p75NTR) causes neuronal cell death. Here we report that Abeta causes cell death in neuronal hybrid cells transfected with p75NTR, but not in nontransfected cells, and that p75NTR(L401K) cannot mediate Abeta neurotoxicity. We analyzed the cytotoxic pathway by transfecting pertussis toxin (PTX)-resistant G protein alpha subunits in the presence of PTX and identified that Galpha(o), but not Galpha(i), proteins are involved in p75NTR-mediated Abeta neurotoxicity. Further investigation suggested that Abeta neurotoxicity via p75NTR involved JNK, NADPH oxidase, and caspases-9/3 and was inhibited by activity-dependent neurotrophic factor, insulin-like growth factor-I, basic fibroblast growth factor, and Humanin, as observed in primary neuron cultures. Understanding the Abeta neurotoxic mechanism would contribute significantly to the development of anti-AD therapies.
Asunto(s)
Péptidos beta-Amiloides/metabolismo , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos , Neuronas/metabolismo , Receptores de Factor de Crecimiento Nervioso/metabolismo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Animales , Caspasas/metabolismo , Muerte Celular/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gi-Go , Proteínas de Unión al GTP Heterotriméricas/genética , Humanos , Células Híbridas , Immunoblotting , Péptidos y Proteínas de Señalización Intracelular , MAP Quinasa Quinasa 4 , Ratones , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Mutación , NADPH Oxidasas/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Neuronas/patología , Neuropéptidos , Oligopéptidos , Proteínas/metabolismo , Receptor de Factor de Crecimiento Nervioso , Receptores de Factor de Crecimiento Nervioso/genética , Somatomedinas/metabolismo , TransfecciónRESUMEN
The biological function of full-length amyloid-beta protein precursor (AbetaPP), the precursor of Abeta, is not fully understood. Multiple laboratories have reported that antibody binding to cell surface AbetaPP causes neuronal cell death. Here we examined whether induced dimerization of the cytoplasmic domain of AbetaPP (AbetaPPCD) triggers neuronal cell death. In neurohybrid cells expressing fusion constructs of the epidermal growth factor (EGF) receptor with AbetaPPCD (EGFR/AbetaPP hybrids), EGF drastically enhanced neuronal cell death in a manner sensitive to acetyl-l-aspartyl-l-glutamyl-l-valyl-l-aspartyl-aldehyde (Ac-DEVD-CHO; DEVD), GSH-ethyl ester (GEE), and pertussis toxin (PTX). Dominant-negative apoptosis signal-regulating kinase 1 (ASK1) blocked this neuronal cell death, but not alpha-synuclein-induced cell death. Constitutively active ASK1 (caASK1) caused DEVD/GEE-sensitive cell death in a manner resistant to PTX and sensitive to Humanin, which also suppressed neuronal cell death by EGFR/AbetaPP hybrid. ASK1 formed a complex with AbetaPPCD via JIP-1b, the c-Jun N-terminal kinase (JNK)-interacting protein. EGFR/AbetaPP hybrid-induced and caASK1-induced neuronal cell deaths were specifically blocked by SP600125 (anthra[1,9-cd]pyrazol-6(2H)-one), a specific JNK inhibitor. Combined with our earlier study, these data indicate that dimerization of AbetaPPCD triggers ASK1/JNK-mediated neuronal cell death. We also noticed a potential role of ASK1/JNK in sustaining the activity of this mechanism after initial activation by AbetaPP, which allows for the achievement of cell death by short-term anti-AbetaPP antibody treatment. Understanding the function of AbetaPPCD and its downstream pathway should lead to effective anti-Alzheimer's disease therapeutics.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Precursor de Proteína beta-Amiloide/farmacología , Quinasas Quinasa Quinasa PAM/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Neuronas/efectos de los fármacos , Transducción de Señal/fisiología , Enfermedad de Alzheimer , Animales , Antracenos/farmacología , Proteínas Portadoras/metabolismo , Dimerización , Factor de Crecimiento Epidérmico/farmacología , Receptores ErbB/genética , Flavonoides/farmacología , Humanos , Células Híbridas , Imidazoles/farmacología , Péptidos y Proteínas de Señalización Intracelular , Proteínas Quinasas JNK Activadas por Mitógenos , MAP Quinasa Quinasa Quinasa 5 , Ratones , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Neuronas/metabolismo , Oligopéptidos/farmacología , Estructura Terciaria de Proteína , Proteínas/farmacología , Piridinas/farmacología , Ratas , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Amyloid precursor protein (APP), the precursor of Abeta, has been shown to function as a cell surface receptor that mediates neuronal cell death by anti-APP antibody. The c-Jun N-terminal kinase (JNK) can mediate various neurotoxic signals, including Abeta neurotoxicity. However, the relationship of APP-mediated neurotoxicity to JNK is not clear, partly because APP cytotoxicity is Abeta independent. Here we examined whether JNK is involved in APP-mediated neuronal cell death and found that: (i) neuronal cell death by antibody-bound APP was inhibited by dominant-negative JNK, JIP-1b and SP600125, the specific inhibitor of JNK, but not by SB203580 or PD98059; (ii) constitutively active (ca) JNK caused neuronal cell death and (iii) the pharmacological profile of caJNK-mediated cell death closely coincided with that of APP-mediated cell death. Pertussis toxin (PTX) suppressed APP-mediated cell death but not caJNK-induced cell death, which was suppressed by Humanin, a newly identified neuroprotective factor which inhibits APP-mediated cytotoxicity. In the presence of PTX, the PTX-resistant mutant of Galphao, but not that of Galphai, recovered the cytotoxic action of APP. These findings demonstrate that JNK is involved in APP-mediated neuronal cell death as a downstream signal transducer of Go.