RESUMO
BACKGROUND: Bathing is a deeply ingrained custom among Japanese; however, data on the incidence rate of symptoms and accidents during bathing have not yet been reported for the Japanese general public. METHODS: We conducted a population-based cross-sectional study of 617 Japanese adults who attended a specialized health checkup. Participants completed a self-administered questionnaire to assess weekly frequencies of bathtub bathing and showering and the frequency of symptoms/accidents (falling, loss of consciousness, and other) during these activities in the past year. We calculated the incidence rates of accidents per 10 000 baths/showers and 95% confidence intervals (CIs) and compared the clinical characteristics of participants who had symptoms/accidents with those who did not. RESULTS: The incidence rates of accidents per 10 000 bathtub baths and showers were 0.43 (95% CI: 0.22-0.84) and 0.24 (95% CI: 0.04-1.37). Although these rates are low, there were 740 000 bathtub bathing-related accidents in Japan, due to the fact that bathing is an almost-daily habit. There was no significant difference in clinical characteristics between groups. CONCLUSIONS: We collected basic information on the incidence of bathing-related accidents in Japan. Falls and loss of consciousness during bathing or showering can potentially lead to a serious accident, so the general public should be educated about the possibility of such accidents during bathing.
Assuntos
Acidentes por Quedas/estatística & dados numéricos , Acidentes Domésticos/estatística & dados numéricos , Banhos/estatística & dados numéricos , Adulto , Idoso , Intervalos de Confiança , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Saúde Pública , Autoavaliação (Psicologia) , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Many studies have reported an association between physical activity and cardiovascular disease (CVD); however, the effect of physical activity remains controversial. Few such studies have been conducted in Japan. Therefore, we examined the relationship between physical activity and death from CVD using prospective data from a Japanese population. METHODS: From a prospective cohort study that comprised 12 490 participants, data from 9810 were analyzed. From April 1992 through July 1995, a baseline survey was conducted in 12 communities in Japan. The participants were followed up until December 2005. Physical activity was assessed using the physical activity index (PAI). PAI scores were grouped in quartiles: Q1 was the lowest PAI quartile and Q4 was the highest. Hazard ratios (HRs) for death from CVD, stroke, and myocardial infarction (MI) were calculated for all PAI quartiles. RESULTS: The mean follow-up period was 11.9 years, during which time 194 participants died of CVD. With Q1 as the reference, the HRs for death from CVD in Q2, Q3, and Q4, were 0.62 (95% confidence interval, 0.40-0.98), 0.53 (0.31-0.88), and 0.40 (0.22-0.73), respectively, in men, and 0.71 (0.38-1.32), 0.52 (0.26-1.04), and 0.48 (0.22-1.05), respectively, in women. The HRs for death from CVD subtypes were similar but not statistically significant. CONCLUSIONS: Among a Japanese population, physical activity was associated with a decreased risk of death from CVD. However, more evidence is needed to elucidate the relationships between physical activity and CVD subtypes.
Assuntos
Doenças Cardiovasculares/mortalidade , Exercício Físico , Infarto do Miocárdio/mortalidade , Acidente Vascular Cerebral/mortalidade , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Saúde da População RuralRESUMO
Amyloid-beta peptide (Abeta) is thought to be linked to the pathogenesis of Alzheimer's disease. Recent studies suggest that Abeta has important physiological roles in addition to its pathological roles. We recently demonstrated that Abeta42 protects hippocampal neurons from glutamate-induced neurotoxicity, but the relationship between Abeta42 assemblies and their neuroprotective effects remains largely unknown. In this study, we prepared non-fibrillar and fibrillar Abeta42 based on the results of the thioflavin T assay, Western blot analysis, and atomic force microscopy, and examined the effects of non-fibrillar and fibrillar Abeta42 on glutamate-induced neurotoxicity. Non-fibrillar Abeta42, but not fibrillar Abeta42, protected hippocampal neurons from glutamate-induced neurotoxicity. Furthermore, non-fibrillar Abeta42 decreased both neurotoxicity and increases in the intracellular Ca(2+) concentration induced by N-methyl-d-aspartate (NMDA), but not by alpha-amino-3-hydrozy-5-methyl-4-isoxazole propionic acid (AMPA). Our results suggest that non-fibrillar Abeta42 protects hippocampal neurons from glutamate-induced neurotoxicity through regulation of the NMDA receptor.
Assuntos
Peptídeos beta-Amiloides/fisiologia , Hipocampo/metabolismo , N-Metilaspartato/toxicidade , Neurônios/metabolismo , Fragmentos de Peptídeos/fisiologia , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/toxicidade , Peptídeos beta-Amiloides/farmacologia , Animais , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Microscopia de Força Atômica , Neurônios/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Receptores de N-Metil-D-Aspartato/biossínteseRESUMO
BACKGROUND: In April 2008, a new health check-up and health guidance system was introduced by the Japanese Government to promote increased physical activity. However, few studies have documented the health benefits of physical activity in Asian populations. We examined the association between all-cause mortality and level of physical activity in a Japanese multicommunity population-based study. METHODS: The Jichi Medical School Cohort Study is a multicommunity, population-based study based in 12 districts in Japan. Baseline data from 4222 men and 6609 women (mean age, 54.8 and 55.0 years, respectively) were collected between April 1992 and July 1995. The participants were followed for a mean duration of 11.9 years. To determine the association between all-cause mortality and level of physical activity, crude mortality rates per 1000 person-years and hazard ratios (HRs) with 95% confidence intervals (CI) were determined using the Cox proportional hazards model. Physical activity was categorized by using physical activity index (PAI) quartiles. The lowest (first) PAI quartile was defined as the HR reference. RESULTS: In men, the lowest mortality rate was observed in the third quartile, with 95 deaths and a crude mortality rate of 7.6; the age- and area-adjusted HR was 0.59 (95% CI, 0.45-0.76), and the mortality curve had a reverse J shape. In women, the lowest mortality rate was observed in the highest PAI quartile, with 69 deaths and a crude mortality rate of 3.5; the HR was 0.81 (95% CI, 0.58-1.12). CONCLUSION: Our results suggest that increased physical activity lowers the risk for all-cause death in Japanese.
Assuntos
Mortalidade , Atividade Motora , Distribuição por Idade , Idoso , Causas de Morte , Estudos de Coortes , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Microglia are believed to play an important role in the regulation of phagocytosis, neuronal survival, neuronal cell death, and inflammation. Recent studies have demonstrated that microglia are multipotential stem cells that give rise to neurons, astrocytes, and oligodendrocytes. However, the functional properties of neurons derived from microglia are poorly understood. In this study, we investigated the possibility that microglia differentiate into functional neurons. Immunocytochemical study demonstrated that microtubule-associated protein 2 (MAP2)-positive cells were derived from microglia under differentiation conditions. Intracellular Ca(2+) imaging study demonstrated that KCl caused no significant changes in [Ca(2+)](i) in microglia, whereas it caused a remarkable increase in [Ca(2+)](i) in microglia-derived cells. Furthermore, electrophysiological study demonstrated that the spike waveform, firing rate, and tetrodotoxin sensitivity of extracellular action potentials evoked by 4-aminopyridine from microglia-derived MAP2-positive cells were nearly identical to those from cultured cortical neurons. These results suggest that microglia-derived MAP2-positive cells possess properties of functional neurons.
Assuntos
Microglia/citologia , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/fisiologia , Potenciais de Ação , Animais , Canais de Cálcio/fisiologia , Diferenciação Celular , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , RatosRESUMO
Cholinergic hypothesis and amyloid cascade hypothesis are mainly proposed for Alzheimer's disease; however, the relationship between these hypotheses is poorly understood. To address the question of whether amyloid beta-peptide pathology affects cholinergic neurotransmission, we examined the effect of a cholinesterase inhibitor, physostigmine, on field excitatory postsynaptic potentials (EPSPs) evoked by single-pulse stimulation in the CA1 region of the hippocampus of various APPswe/PS1dE9 transgenic mice with different degrees of amyloid beta-peptide pathology. Reduced field EPSPs by physostigmine in transgenic mice at 3 months of age, when the mice had negligible amyloid beta-peptide levels and no amyloid beta-peptide deposits, were indistinguishable from those in age-matched wild-type mice. In contrast, reduced field EPSPs by physostigmine in transgenic mice at 5 months of age, when the mice had low amyloid beta-peptide levels and subtle amyloid beta-peptide deposits, were significantly lower than those in age-matched wild-type mice. Next, we characterized acetylcholine receptors, which play important roles in cholinergic neurotransmission, because physostigmine resulted in increased acetylcholine levels in the synaptic cleft. Different reductions of field EPSPs by physostigmine between transgenic and wild-type mice at 5 months of age were not affected by a nicotinic receptor antagonist, mecamylamine; however, reduced field EPSPs by physostigmine in both transgenic and wild-type mice were restored to basal levels by a muscarinic receptor antagonist, atropine. These results indicate that cholinergic modulation of glutamatergic transmission is already impaired at the onset of the formation of amyloid beta-peptide deposits, and muscarinic receptor dysfunction is one of the causes of this impairment.
Assuntos
Doença de Alzheimer/fisiopatologia , Precursor de Proteína beta-Amiloide/genética , Presenilina-1/genética , Receptores Muscarínicos/fisiologia , Transmissão Sináptica/fisiologia , Envelhecimento/fisiologia , Doença de Alzheimer/genética , Animais , Western Blotting , Inibidores da Colinesterase/farmacologia , Modelos Animais de Doenças , Estimulação Elétrica , Eletrofisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Ácido Glutâmico/fisiologia , Técnicas In Vitro , Camundongos , Camundongos Transgênicos , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Técnicas de Patch-Clamp , Fisostigmina/farmacologia , Receptores Muscarínicos/genética , Receptores Nicotínicos/efeitos dos fármacos , Receptores Nicotínicos/fisiologia , Transmissão Sináptica/genéticaRESUMO
Showering is the most common form of bathing worldwide. Whole-body immersion bathing in warm water (~40°C) is common in Japan and exerts sufficient hyperthermic action to induce vasodilatation and increase blood flow, supplying more oxygen and nutrients to the periphery. Cross-sectional studies report better subjective health status with an immersion bathing habit. This randomized controlled trial compared the effects on health of immersion bathing and shower bathing in 38 participants who received 2-week intervention of immersion bathing in warm water (40°C) for 10 min (bathing intervention) followed by 2-week shower bathing without immersion (showering intervention) or vice versa (n = 19 each group). Visual analog scale scores were significantly better for fatigue, stress, pain, and smile and tended to be better for self-reported heath and skin condition after bathing intervention than after showering intervention. The SF-8 Health Survey showed significantly better general health, mental health, role emotional, and social functioning scores. Profile of Mood State scores were lower for stress, tension-anxiety, anger-hostility, and depression-dejection. Immersion bathing, but not shower bathing, exerts hyperthermic action that induces increased blood flow and metabolic waste elimination, which may afford physical refreshment. Immersion bathing should improve both physical and emotional aspects of quality of life.
RESUMO
A recent hypothesis suggests that there is impaired hippocampal neurogenesis in Alzheimer's disease. Here we examined the proliferation, the first stage in neurogenesis, of hippocampal progenitor cells in amyloid precursor protein with Swedish mutation and presenilin-1 with deletion of exon 9 (APPswe/PS1dE9) transgenic mice. Compared with age-matched wild-type mice, transgenic mice at 5 months of age with low amyloid beta-peptide (Abeta) levels and subtle Abeta deposits showed normal proliferation of hippocampal progenitor cells; however, transgenic mice at 9 months of age with high Abeta levels and numerous Abeta deposits showed decreased proliferation of these cells. The number of proliferating cells in male transgenic mice was indistinguishable from that in female transgenic mice. These results indicate that neurogenesis is decreased with degrees of Abeta pathology, and that there is no gender difference in their proliferation in APPswe/PS1dE9 transgenic mice.
Assuntos
Hipocampo/fisiologia , Presenilina-1/genética , Presenilina-1/fisiologia , Células-Tronco/fisiologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/fisiologia , Amiloidose/patologia , Animais , Antimetabólitos , Bromodesoxiuridina , Proliferação de Células , Éxons/genética , Feminino , Deleção de Genes , Hipocampo/citologia , Hipocampo/patologia , Masculino , Camundongos , Camundongos Transgênicos , Caracteres SexuaisRESUMO
Mulberry leaf has been reported to possess medicinal properties, including hypoglycemic, hypotensive and diuretic effects. Little is known, however, about its medicinal properties for central nervous system disorders, including Alzheimer's disease. Accumulating evidence suggests that amyloid beta-peptide (1-42) plays an important role in the etiology of Alzheimer's disease. Here we show that mulberry leaf extract inhibits the amyloid beta-peptide (1-42) fibril formation by both the thioflavin T fluorescence assay and atomic force microscopy. Furthermore, mulberry leaf extract protected hippocampal neurons against amyloid beta-peptide (1-42)-induced cell death in a concentration-dependent manner. These results suggest that mulberry leaf extract provides a viable treatment for Alzheimer's disease through the inhibition of amyloid beta-peptide (1-42) fibril formation and attenuation of amyloid beta-peptide (1-42)-induced neurotoxicity.
Assuntos
Peptídeos beta-Amiloides/toxicidade , Morus/química , Emaranhados Neurofibrilares/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Extratos Vegetais/farmacologia , Animais , Benzotiazóis , Contagem de Células/métodos , Células Cultivadas , Relação Dose-Resposta a Droga , Interações Medicamentosas , Embrião de Mamíferos , Hipocampo/citologia , Camundongos , Camundongos Endogâmicos ICR , Microscopia de Força Atômica/métodos , Neurônios/efeitos dos fármacos , Tiazóis/metabolismoRESUMO
We have previously identified Ntan1 as a magnetism response gene by differential display screening in cultured rat hippocampal neurons. Ntan1 mRNA was ubiquitously expressed in all the mouse tissues examined but relatively abundant in brain, retina and testis. Ntan1 mRNA expression was detectable in the embryonic 12-day mouse brain and gradually increased with ageing. In situ hybridization analysis showed high localization of Ntan1 mRNA in pyramidal cell layer of CA region and granular cell layer of dentate gyrus in the hippocampus, and Purkinje and granular cell layers in the cerebellum, respectively. Ntan1 mRNA expression was significantly increased about two-fold 12 h after brief exposure for 15 min to magnetism at 100 mT with a gradual decrease thereafter in cultured mouse hippocampal neurons. When embryonic 12-day-old or newborn mice were successively exposed to magnetic fields at 100 mT for 2 h, four times per day until the postnatal seventh day, Ntan1 mRNA was significantly increased about 1.5-2-fold in the hippocampus in vivo. The mice exposed to magnetic fields under the same condition showed significantly decreased locomotor activity. These results suggest that magnetic exposure affects higher order neural functions through modulation of genes expression.
Assuntos
Amidoidrolases/genética , Química Encefálica/genética , Campos Eletromagnéticos , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos da radiação , Northern Blotting , Células Cultivadas , Feminino , Expressão Gênica/efeitos da radiação , Hibridização In Situ , Masculino , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/fisiologia , Neurônios/efeitos da radiação , Gravidez , RNA Complementar/biossíntese , RNA Complementar/genética , RNA Complementar/metabolismo , Distribuição TecidualRESUMO
OBJECTIVE: Programs to support independent living for elderly people are generally designed taking into account physical and psychological conditions. The interests of individuals are diverse even when the physical conditions are the same. Interests in daily life are important factors for adequate planning of the programs for independent living. The purpose of this study was to examine an evaluation structure of interests of Japanese elderly people in their daily life. METHODS: Focus group interviews were conducted to collect items for interests in daily life by several researchers targeting activity groups of elderly people. Eighteen items were extracted from a total of 50 following the principles: (1) Items with similar meanings are brought together; (2) Items which might have big differences in meaning depending on the subject were excluded; and (3) Items which were double barreled were excluded. The questionnaire 18 items were designed to give a 4-point Likart scale for answers from "very important" to "not important at all". The survey was conducted in 20 municipalities all over Japan in 2000. From residents aged 65 years and over, 6,094 individuals were selected randomly as the study population. RESULTS: Of 5,565 participants, 4,527 individuals answered all 18 items. "To have a good time with the family" was the favorite answer (54.8%), rated as "very important". Four factors (eigenvalue > 1) were extracted by applying principal component analysis: "to live with good communication", "to achieve one's purpose", "to live socially", and "to live comfortably". "To live with good communication" showed the highest score and "To live socially" showed the lowest score. CONCLUSION: With this scale, we could precisely determine the diversity of interests of Japanese elderly people in their daily life. We suggest that this scale might be useful not only to analyze the interests of individuals, but also to plan programs in terms of quality of life or independent living in late life.
Assuntos
Idoso/psicologia , Testes Psicológicos , Atividades Cotidianas , Idoso de 80 Anos ou mais/psicologia , Feminino , Felicidade , Humanos , Entrevistas como Assunto , Japão , Masculino , Qualidade de Vida , Pesos e MedidasRESUMO
Hot spring water and natural mineral water have been therapeutically used to prevent or improve various diseases. Specifically, consumption of bicarbonate-rich mineral water (BMW) has been reported to prevent or improve type 2 diabetes (T2D) in humans. However, the molecular mechanisms of the beneficial effects behind mineral water consumption remain unclear. To elucidate the molecular level effects of BMW consumption on glycemic control, blood metabolome analysis and fecal microbiome analysis were applied to the BMW consumption test. During the study, 19 healthy volunteers drank 500 mL of commercially available tap water (TW) or BMW daily. TW consumption periods and BMW consumption periods lasted for a week each and this cycle was repeated twice. Biochemical tests indicated that serum glycoalbumin levels, one of the indexes of glycemic controls, decreased significantly after BMW consumption. Metabolome analysis of blood samples revealed that 19 metabolites including glycolysis-related metabolites and 3 amino acids were significantly different between TW and BMW consumption periods. Additionally, microbiome analysis demonstrated that composition of lean-inducible bacteria was increased after BMW consumption. Our results suggested that consumption of BMW has the possible potential to prevent and/or improve T2D through the alterations of host metabolism and gut microbiota composition.
RESUMO
OBJECTIVE: To determine factors affecting self-rated health among the non-institutionalized elderly in Japan. METHODS: In 20 municipalities in Japan, 6,094 persons aged 65 years and older who were not institutionalized were selected at random. A questionnaire survey was conducted from September through November 2000. The distribution of self-rated health was rated in terms of dependent variables, with odds ratios and their 95% confidence intervals calculated using unconditional logistic models. RESULTS: Of the study population, 5,565 persons (91.8%) responded to the survey. Of the respondents, 64.4% answered that they were healthy, while 28.8% were not. The necessity for periodical visit to hospitals and clinics, and lowering of the activity of daily living greatly lowered self-rated health. Compared with those who were 85 years of age or older, a high health status was observed among those aged between 75 and 84 years, but not those aged 65 to 74 years. Those who tried to have exercise periodically, who had a vice-leadership role in a group, who joined social activities, who lived what they considered a worthwhile life, and who had positive positive activities in daily life, had high levels of self-rated health. Joining social activities for passive reasons elevated the health as well as joining for active reasons such as "because it is fun." CONCLUSION: Even if the reason is passive, joining social activities may elevate the self-rated health levels of elderly people.
Assuntos
Idoso/psicologia , Nível de Saúde , Idoso de 80 Anos ou mais , Feminino , Humanos , Relações Interpessoais , MasculinoRESUMO
The purpose of this study was to assess the quality of study reports on spa therapy based on randomized controlled trials by the spa therapy and balneotherapy checklist (SPAC), and to show the relationship between SPAC score and the characteristics of publication. We searched the following databases from 1990 up to September 30, 2013: MEDLINE via PubMed, CINAHL, Web of Science, Ichushi Web, Global Health Library, the Western Pacific Region Index Medicus, PsycINFO, and the Cochrane Database of Systematic Reviews. We used the SPAC to assess the quality of reports on spa therapy and balneotherapy trials (SPAC) that was developed using the Delphi consensus method. Fifty-one studies met all inclusion criteria. Forty studies (78%) were about "Diseases of the musculoskeletal system and connective)". The total SPAC score (full-mark; 19 pts) was 10.8 ± 2.3 pts (mean ± SD). The items for which a description was lacking (very poor; <50%) in many studies were as follows: "locations of spa facility where the data were collected"; "pH"; "scale of bathtub"; "presence of other facility and exposure than bathing (sauna, steam bath, etc.)"; "qualification and experience of care provider"; "Instructions about daily life" and "adherence". We clarified that there was no relationship between the publish period, languages, and the impact factor (IF) for the SPAC score. In order to prevent flawed description, SPAC could provide indispensable information for researchers who are going to design a research protocol according to each disease.
Assuntos
Balneologia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Lista de Checagem , Humanos , Projetos de PesquisaRESUMO
Japan is a major tea producing country, and green tea is known for its health benefits which are believed to be due to catechins. However, difficulties in maintaining an adequate amount of catechins in the blood have been reported. Another important health-promoting activity among the Japanese is bathing in hot springs. This pilot study examined whether the combined effects of green tea consumption and hot spring bathing improved absorption of green tea catechins. The study, with a comparative within-subject design involving two different intervention trials--green tea consumption with hot spring bathing and only green tea consumption--was conducted on 2 separate days. Plasma levels of catechin; (-)-epigallocatechin-3-O-gallate (EGCG) were analyzed from four volunteers. Plasma EGCG concentration was found to be higher for the combined trial of green tea consumption and hot spring bathing.
Assuntos
Banhos , Camellia sinensis/química , Catequina/análogos & derivados , Fontes Termais , Extratos Vegetais/sangue , Adulto , Disponibilidade Biológica , Catequina/sangue , Catequina/farmacocinética , Feminino , Humanos , Absorção Intestinal , Masculino , Projetos Piloto , Extratos Vegetais/farmacocinéticaRESUMO
BACKGROUND: Bathing, or soaking, in a bathtub is a popular and often habitual pastime that has its roots in the culture of the Japanese people. The purpose of this study was to examine the effects of such bathing on health status. METHODS: We conducted a population-based cross-sectional study involving 617 Japanese participants who took routine medical checkups. The frequency of bathing in a bathtub was categorized into two levels: "less than seven times a week" (less frequent bathing group) and "seven or more times a week" (frequent bathing group). We compared the following characteristics between the two groups: age, body mass index, blood pressure, blood chemistry findings, self-rated health, and sleep quality. RESULTS: The frequent bathing group reported better self-rated health and sleep quality than the less frequent bathing group, with age- and sex-adjusted odds ratios (95% confidence interval) of 2.11 (1.28-3.48) for self-rated health and 1.55 (0.98-2.44) for sleep quality. Other survey items were similar between the two groups. CONCLUSIONS: The findings of this study suggested that bathing in a bathtub every day or more frequently was associated with a good state of self-rated health and sleep quality.
Assuntos
Banhos , Nível de Saúde , Sono , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de TempoRESUMO
Amyloid beta-peptide (Abeta) and glutamate are generally believed to be closely related to the pathogenesis of Alzheimer's disease and cerebrovascular disease, respectively. Recent advances suggest that risk factors linked to cerebrovascular disease significantly increase the risk of developing Alzheimer's disease. In this study, we examined the effects of pretreatment of cultured hippocampal neurons with Abeta(1-42) (0.3, 0.5, and 1.0microM) for 3h (Abeta preconditioning) on glutamate-induced neurotoxicity. Abeta preconditioning significantly reduced both glutamate-induced neurotoxicity and the glutamate-induced increase in intracellular Ca(2+) concentration ([Ca(2+)](i)). Abeta preconditioning significantly reduced cell surface expression of N-methyl-d-aspartate (NMDA) glutamate receptor subunit protein NR1, although it exerted no significant effect on the total expression of NR1. These results suggest that Abeta preconditioning reduced glutamate-induced neurotoxicity by promoting endocytosis of NMDA receptor, followed by inhibition of the increase in [Ca(2+)](i). Our results support the notion of an association between Alzheimer's disease and cerebrovascular disease, and suggest a new mechanism for neuroprotection by promoting endocytosis of NMDA receptor.
Assuntos
Peptídeos beta-Amiloides/administração & dosagem , Ácido Glutâmico/administração & dosagem , Neurônios/citologia , Neurônios/fisiologia , Fragmentos de Peptídeos/administração & dosagem , Receptores de N-Metil-D-Aspartato/metabolismo , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Camundongos , Camundongos Endogâmicos ICR , Neurônios/efeitos dos fármacos , Neurotoxinas/administração & dosagemRESUMO
In order to elucidate mechanisms underlying modulation by static magnetism of the cellular functionality and/or integrity in the brain, we screened genes responsive to brief magnetism in cultured rat hippocampal neurons using differential display analysis. We have for the first time cloned and identified Ntan1 (amidohydrolase for N-terminal asparagine) as a magnetism responsive gene in rat brain. Ntan1 is an essential component of a protein degradation signal, which is a destabilizing N-terminal residue of a protein, in the N-end rule. In situ hybridization histochemistry revealed abundant expression of Ntan1 mRNA in hippocampal neurons in vivo. Northern blot analysis showed that Ntan1 mRNA was increased about three-fold after 3 h in response to brief magnetism. Brief magnetism also increased the transcriptional activity of Ntan1 promoter by luciferase reporter assay. Brief magnetism induced degradation of microtubule-associated protein 2 (MAP2) without affecting cell morphology and viability, which was prevented by a selective inhibitor of 26S proteasome in hippocampal neurons. Overexpression of Ntan1 using recombinant Ntan1 adenovirus vector resulted in a marked decrease in the MAP2 protein expression in hippocampal neurons. Our results suggest that brief magnetism leads to the induction of Ntan1 responsible for MAP2 protein degradation through ubiquitin-proteasome pathway in rat hippocampal neurons.
Assuntos
Amidoidrolases/efeitos da radiação , Campos Eletromagnéticos/efeitos adversos , Proteínas Associadas aos Microtúbulos/metabolismo , Neurônios/efeitos da radiação , Complexo de Endopeptidases do Proteassoma/efeitos da radiação , Ubiquitina/efeitos da radiação , Amidoidrolases/genética , Amidoidrolases/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Sobrevivência Celular/fisiologia , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Inibidores Enzimáticos/farmacologia , Vetores Genéticos/fisiologia , Hipocampo/enzimologia , Hipocampo/efeitos da radiação , Imageamento por Ressonância Magnética/efeitos adversos , Proteínas Associadas aos Microtúbulos/efeitos da radiação , Dados de Sequência Molecular , Neurônios/enzimologia , Regiões Promotoras Genéticas/fisiologia , Regiões Promotoras Genéticas/efeitos da radiação , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/efeitos da radiação , Ratos , Ativação Transcricional/fisiologia , Ativação Transcricional/efeitos da radiação , Ubiquitina/metabolismo , Regulação para Cima/fisiologia , Regulação para Cima/efeitos da radiaçãoRESUMO
In rat hippocampal neurons cultured with the antagonist for N-methyl-D-aspartate (NMDA) receptors dizocilpine (MK-801) for 8 days in vitro (DIV), a significant decrease was seen in the expression of microtubule-associated protein-2 (MAP-2) as well as mRNA for both brain-derived neurotrophic factor (BDNF) and growth-associated protein-43 (GAP-43), in addition to decreased viability. MK-801 not only decreased the expression of the NR1 subunit of NMDA receptors but also increased NR2A expression, without affecting NR2B expression. Repetitive daily exposure to static magnetic fields at 100 mT for 15 min led to a decrease in the expression of MAP-2, without significantly affecting cell viability or the expression of neuronal nuclei (NeuN) and GAP-43. However, the repetitive magnetism prevented decreases in both BDNF mRNA and MAP-2 and additionally increased the expression of NR2A subunit, without altering NR1 expression in neurons cultured in the presence of MK-801. Repetitive magnetism was also effective in preventing the decrease by MK-801 in the ability of NMDA to increase intracellular free Ca2+ ions, without affecting the decrease in the maximal response. These results suggest that repetitive magnetism may at least in part counteract the neurotoxicity of MK-801 through modulation of the expression of particular NMDA receptor subunits in cultured rat hippocampal neurons.