RESUMO
Aging-associated declines in cognitive, emotional, and cardiovascular function are well known. Environmental stress triggers critical changes in the brain, further compromising cardiovascular and behavioral health during aging. Excessive dietary salt intake is one such stressor. Here, we tested the effect of high salt (HS) on anxiety, learning-memory function, and blood pressure (BP) in male Fischer brown Norway (FBN) rats. Adult (A; 2 mo) and old (O; 20 mo) male rats were fed normal-salt (NS; 0.4% NaCl) or HS (8% NaCl) diets for 4 wk after being implanted with telemeter probes for conscious BP measurement. Thereafter, tests to assess anxiety-like behavior and learning-memory were conducted. The rats were then killed, and samples of plasma, urine, and brain tissue were collected. We found that systolic BP was higher in O-NS (117 ± 1.2 mm Hg) than in A-NS (105 ± 0.8 mm Hg) rats (P < 0.05). Furthermore, BP was higher in O-HS (124 ± 1.4 mm Hg) than in O-NS (117 ± 1.2 mm Hg) rats (P < 0.05). Moreover, anxiety-like behavior (light-dark and open-field tests) was not different between A-NS and O-NS rats but was greater in O-HS rats than in A-NS, O-NS, or A-HS rats (P < 0.05). Short-term memory (radial arm water maze test) was similar in A-NS and O-NS rats but was significantly impaired in O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05). Furthermore, oxidative stress variables (in plasma, urine, and brain) as well as corticosterone (plasma) were greater in O-HS rats when compared with A-NS, O-NS, or A-HS rats (P < 0.05). The antioxidant enzyme glyoxalase-1 expression was selectively reduced in the hippocampus and amygdala of O-HS rats compared with A-NS, O-NS, or A-HS rats (P < 0.05), whereas other antioxidant enzymes, glutathione reductase 1, manganese superoxide dismutase (SOD), and Cu/Zn SOD remained unchanged. We suggest that salt-sensitive hypertension and behavioral derangement are associated with a redox imbalance in the brain of aged FBN rats.
Assuntos
Envelhecimento , Ansiedade , Dieta , Hipertensão , Memória de Curto Prazo , Cloreto de Sódio na Dieta/efeitos adversos , 8-Hidroxi-2'-Desoxiguanosina , Animais , Ansiedade/fisiopatologia , Pressão Sanguínea , Corticosterona/sangue , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Dinoprosta/análogos & derivados , Dinoprosta/sangue , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glutationa Redutase/metabolismo , Hipertensão/fisiopatologia , Lactoilglutationa Liase/metabolismo , Aprendizagem , Masculino , Estresse Oxidativo , Ratos , Cloreto de Sódio na Dieta/administração & dosagem , Superóxido Dismutase/metabolismoRESUMO
We examined whether or not grape powder treatment ameliorates oxidative stress-induced anxiety-like behavior, memory impairment, and hypertension in rats. Oxidative stress in Sprague-Dawley rats was produced by using L-buthionine-(S,R)-sulfoximine (BSO). Four groups of rats were used: 1) control (C; injected with vehicle and provided with tap water), 2) grape powder-treated (GP; injected with vehicle and provided for 3 wk with 15 g/L grape powder dissolved in tap water), 3) BSO-treated [injected with BSO (300 mg/kg body weight), i.p. for 7 d and provided with tap water], and 4) BSO plus grape powder-treated (GP+BSO; injected with BSO and provided with grape powder-treated tap water). Anxiety-like behavior was significantly greater in BSO rats compared with C or GP rats (P < 0.05). Grape powder attenuated BSO-induced anxiety-like behavior in GP+BSO rats. BSO rats made significantly more errors in both short- and long-term memory tests compared with C or GP rats (P < 0.05), which was prevented in GP+BSO rats. Systolic and diastolic blood pressure was significantly greater in BSO rats compared with C or GP rats (P < 0.05), whereas grape powder prevented high blood pressure in GP+BSO rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK-1/2) was activated (P < 0.05), whereas levels of glyoxalase-1 (GLO-1), glutathione reductase-1 (GSR-1), calcium/calmodulin-dependent protein kinase type IV (CAMK-IV), cAMP response element-binding protein (CREB), and brain-derived neurotrophic factor (BDNF) were significantly less (P < 0.05) in BSO but not in GP+BSO rats compared with C or GP rats. We suggest that by regulating brain ERK-1/2, GLO-1, GSR-1, CAMK-IV, CREB, and BDNF levels, grape powder prevents oxidative stress-induced anxiety, memory impairment, and hypertension in rats.
Assuntos
Ansiedade/prevenção & controle , Frutas/química , Hipertensão/prevenção & controle , Transtornos da Memória/prevenção & controle , Estresse Oxidativo/fisiologia , Vitis/química , Animais , Ansiedade/etiologia , Comportamento Animal , Química Encefálica , Fator Neurotrófico Derivado do Encéfalo/análise , Butionina Sulfoximina/administração & dosagem , Proteína Quinase Tipo 4 Dependente de Cálcio-Calmodulina/análise , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/análise , Suplementos Nutricionais , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Alimentos em Conserva , Liofilização , Glutationa Redutase/análise , Hipertensão/etiologia , Lactoilglutationa Liase/análise , Masculino , Transtornos da Memória/etiologia , Polifenóis/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: The relationship between sickle cell disease (SCD) and severe pre-eclampsia is poorly established. It is also unknown whether the occurrence of HIV infection among women with SCD modifies their risk level for severe pre-eclampsia. We hypothesized that pregnant women with SCD are at an elevated risk for severe pre-eclampsia as a result of heightened endothelial damage; and the combination of SCD-HIV augments the inflammatory processes of endothelial damage leading to amplified risk for severe pre-eclampsia. STUDY DESIGN: We analyzed more than 57 million pregnancy-related hospitalizations and births in the US from January 1, 2002 through December 31, 2014. MAIN OUTCOME MEASURES: We applied multivariable survey logistic regression to generate odds ratios for the association between SCD, HIV and SCD-HIV status and severe pre-eclampsia with adjustment for potential confounders. RESULTS: Of the total 57,326,459 pregnant women, 57,198,505 (99.78%) did not have SCD or HIV, 73,064 (12.7 per 10,000) had HIV only, 54,890 (9.58 per 10,000) had SCD only and 222 (0.39 per 100,000) had both SCD and HIV. Mothers with SCD and HIV-SCD experienced a significant elevation in risk for severe pre-eclampsia of about 60% (ORâ¯=â¯1.61; 95% CIâ¯=â¯1.44, 1.79) and of more than 300% (ORâ¯=â¯4.28; 95% CIâ¯=â¯1.35, 13.62) respectively. CONCLUSION: In the largest study on SCD and pre-eclampsia in the world, we established SCD to be strongly associated with severe pre-eclampsia. Another unique finding is the synergistic effect of amplified risk for severe pre-eclampsia among mothers with the combined SCD-HIV status.
Assuntos
Anemia Falciforme/epidemiologia , Infecções por HIV/epidemiologia , Pré-Eclâmpsia/epidemiologia , Adolescente , Adulto , Anemia Falciforme/diagnóstico , Bases de Dados Factuais , Feminino , Infecções por HIV/diagnóstico , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Pré-Eclâmpsia/diagnóstico , Gravidez , Prevalência , Prognóstico , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Post-traumatic stress disorder (PTSD) is a condition which can develop from exposure to a severe traumatic event such as those occurring during wars or natural disasters. Benzodiazepines and selective serotonin reuptake inhibitors (SSRIs) are considered the gold standard for PTSD treatment, but their side effects pose a serious problem. While regular physical exercise is regarded as a mood elevator and known to enhance cognitive function, its direct role in rescuing core symptoms of PTSD including anxiety and depression-like behaviors and cognitive impairment is unclear. In the present study using the single-prolonged stress (SPS) rat model of PTSD (2h restrain, 20 min forced swimming, 15 min rest, and 1-2 min diethyl ether exposure), we examined the beneficial effect of moderate treadmill exercise on SPS-induced behavioral deficits including anxiety and depression-like behaviors and memory impairment. Male Wistar rats were randomly assigned into four groups: control (sedentary), exercised, SPS (no exercise), or SPS-exercised. Rats were exercised on a rodent treadmill for 14 consecutive days. Rats in all groups were tested for anxiety-like behaviors using open field (OF), light-dark and elevated-plus maze tests. All rats were tested for short-term and long-term memory in the radial arm water maze test. Rats were then sacrificed, blood was collected (for corticosterone levels), and individual organs (spleen, adrenals, and thymus) harvested. Results suggest that moderate physical exercise ameliorates SPS-induced behavioral deficits in rats.
Assuntos
Transtornos de Ansiedade/fisiopatologia , Transtorno Depressivo/fisiopatologia , Atividade Motora/fisiologia , Transtornos de Estresse Pós-Traumáticos/fisiopatologia , Anedonia/fisiologia , Animais , Transtornos de Ansiedade/terapia , Corticosterona/sangue , Transtorno Depressivo/terapia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Transtornos da Memória/fisiopatologia , Transtornos da Memória/terapia , Memória de Curto Prazo/fisiologia , Testes Neuropsicológicos , Distribuição Aleatória , Ratos Wistar , Transtornos de Estresse Pós-Traumáticos/terapia , Resultado do TratamentoRESUMO
Social defeat (SD) induced stress causes physiological and behavioral deficits in rodents, including depression and anxiety-like behaviors, as well as memory impairment. Anxiolytic and mood elevating effects of physical exercise are also known. However, rescue effect of physical exercise in social defeat-induced anxiety, depression or memory impairment has not been addressed. The role of epigenetic mechanisms that potentially contribute to these rescue or protective effects is also not known. The present study investigated the effect of moderate treadmill exercise on anxiety-like behavior and memory function in rats subjected to SD using a modified version of the resident-intruder model for social stress (defeat). Changes in histone acetylation and histone-modifying enzymes were examined in hippocampus, amygdala and frontal cortex which are considered critical for anxiety, depression and cognition. Sprague Dawley rats were randomly assigned in four groups; control, exercised, social defeat, social defeat and exercise. At the end of the SD or control exposure lasting 30 min daily for 7 days, one group of SD rats was subjected to treadmill exercise for 2 weeks, whereas the other SD group was handled without exercise. Anxiety-like behavior tests and radial arm water maze test suggested that moderate treadmill exercise rescued social defeat induced anxiety-like behavior and memory impairment. Moreover, exercise normalized SD-induced increase in oxidative stress, most likely by adjusting antioxidant response. Our data suggests involvement of epigenetic mechanisms including histone acetylation of H3 and modulation of methyl-CpG-binding in the hippocampus that might contribute to the rescue effects of exercise in SD-induced behavioral deficits in rats.
Assuntos
Transtornos de Ansiedade/fisiopatologia , Hipocampo/fisiopatologia , Transtornos da Memória/fisiopatologia , Atividade Motora/fisiologia , Acetilação , Animais , Transtornos de Ansiedade/terapia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corticosterona/sangue , Dominação-Subordinação , Epigênese Genética/fisiologia , Histonas/metabolismo , Masculino , Aprendizagem em Labirinto/fisiologia , Transtornos da Memória/terapia , Proteína 2 de Ligação a Metil-CpG/metabolismo , Neuroimunomodulação/fisiologia , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Long-Evans , Ratos Sprague-Dawley , Fatores de TempoRESUMO
In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (P<0.05). Socially defeated rats made significantly more errors in long term memory tests (P<0.05) as compared to control rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK1/2), and an inflammatory marker, interleukin (IL)-6 were activated (P<0.05), while the protein levels of glyoxalase (GLO)-1, glutathione reductase (GSR)-1, calcium/calmodulin-dependent protein kinase type (CAMK)-IV, cAMP-response-element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were significantly less (P<0.05) in the hippocampus, but not in the prefrontal cortex and amygdala of socially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats.
Assuntos
Encéfalo/metabolismo , Estresse Oxidativo , Estresse Psicológico/metabolismo , Animais , Ansiedade/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Inflamação , Masculino , Transtornos da Memória/metabolismo , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Predomínio SocialRESUMO
Diminished estrogen influence at menopause is reported to be associated with cognitive decline, heightened anxiety and hypertension. While estrogen therapy is often prescribed to overcome these behavioral and physiological deficits, antioxidants which have been shown beneficial are gaining nutritional intervention and popularity. Therefore, in the present study, utilizing the antioxidant properties of grapes, we have examined effect of 3 weeks of grape powder (GP; 15 g/L dissolved in tap water) treatment on anxiety-like behavior, learning-memory impairment and high blood pressure in ovariectomized (OVX) rats. Four groups of female Wistar rats were used; sham control, sham-GP treated, OVX and OVX+GP treated. We observed a significant increase in systolic and diastolic blood pressure in OVX rats as compared to sham-controls. Furthermore, ovariectomy increased anxiety-like behavior and caused learning and memory impairment in rats as compared to sham-controls. Interestingly, providing grape powder treated water to OVX rats restored both systolic and diastolic blood pressure, decreased anxiety-like behavior and improved memory function. Moreover, OVX rats exhibited an impaired long term potentiation which was restored with grape powder treatment. Furthermore, ovariectomy increased oxidative stress in the brain, serum and urine, selectively decreasing antioxidant enzyme, glyoxalase-1 protein expression in the hippocampus but not in the cortex and amygdala of OVX rats, while grape powder treatment reversed these effects. Other antioxidant enzyme levels, including manganese superoxide dismutase (SOD) and Cu/Zn SOD remained unchanged. We suggest that grape powder by regulating oxidative stress mechanisms exerts its protective effect on blood pressure, learning-memory and anxiety-like behavior. Our study is the first to examine behavioral, biochemical, physiological and electrophysiological outcome of estrogen depletion in rats and to test protective role of grape powder, all in the same study.