RESUMO
BACKGROUND: The metabolic syndrome is defined by the presence of obesity, insulin resistance, dyslipidemia, and hypertension. Advanced glycation end products (AGEs) are stable end products of the Maillard reaction, whereby AGE accumulation is considered not only a biomarker of aging but is also associated with several degenerative diseases. AGEs are recognized by several receptor molecules of which the receptor of AGEs (RAGE) is currently the most intensively studied receptor. Activation of RAGE causes an unfavorable proinflammatory state and deletion of RAGE in diabetic animals has been reported to protect against atherosclerosis. AGEs and a high fat diet are associated with cardiovascular diseases, whereas is still not clear whether a direct link between high fat nutrition and AGEs exists in vivo. MATERIALS AND METHODS: C57BL/6 and C57BL/6 RAGE -/- mice were fed a high fat diet to induce obesity. Weight, insulin, lipid levels, AGE modifications, and cardiac gene expression were analyzed. RESULTS: The absence of RAGE resulted in accelerated weight gain, increased plasma cholesterol, and higher insulin levels in obese mice. The hearts of normal and obese RAGE -/- mice contained lower levels of the AGE arginine-pyrimidine and 3DG-imidazolone than RAGE + / + animals. RAGE -/- mice also exhibited lower expression of the genes encoding the antioxidative enzymes MnSOD, Cu/ZnSOD, and ceruloplasmin in cardiac tissue, whereas the AGE receptors AGER-1, -2, and -3 were equally expressed in both genotypes. Obese mice of both strains expressed increased amounts of AGER-2. Only obese RAGE + / + mice exhibited a reduced mRNA accumulation of Cu/Zn SOD. CONCLUSION: These data suggest that RAGE is involved in the development of obesity and insulin resistance.
Assuntos
Dieta Hiperlipídica/métodos , Gorduras na Dieta/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Obesidade/fisiopatologia , Espécies Reativas de Oxigênio/metabolismo , Receptores Imunológicos/metabolismo , Aumento de Peso , Animais , Camundongos , Camundongos Knockout , Receptor para Produtos Finais de Glicação AvançadaRESUMO
The ovarian hormone estrogen is presumed to modulate processes of learning and memory in adulthood. In this study, we examined the effects of short-term estrogen replacement on associative memory formation. Adult ovariectomized female rats received two injections of estradiol (10, 20 or 40 microg) 24 h apart and were trained 4 h following each injection on the hippocampal-dependent task of trace eyeblink conditioning. Only the highest dose of estrogen, which produced plasma estradiol levels >250 pg/ml, enhanced conditioned responding. One day after the last injection, estrogen treated rats continued to exhibit elevated levels of conditioning and extinguished responding when the conditioned stimulus was no longer presented. Exposure to estrogen did not alter pain sensitivity or activity levels, but did greatly increase uterine weight. These results provide additional support to the view that that ovarian steroids are beneficial to the performance of certain forms of learning and memory tasks, albeit at supraphysiological doses. They are discussed with reference to hormone replacement and its effects on cognitive processes.
Assuntos
Aprendizagem por Associação/fisiologia , Condicionamento Palpebral/fisiologia , Estradiol/fisiologia , Memória/fisiologia , Animais , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Estradiol/sangue , Feminino , Ovariectomia , Ratos , Ratos Sprague-DawleyRESUMO
The peripartum period is accompanied by dramatic changes in hormones and a host of new behaviours in response to experience with offspring. Both maternal experience and maternal hormones can have a significant impact upon the brain and behaviour. This review outlines recent studies demonstrating modifications in hippocampal plasticity across the peripartum period, as well as the putative hormonal mechanisms underlying these changes and their modulation by stress. In addition, the impact of reproductive experience upon the ageing hippocampus is discussed. Finally, we consider how these changes in hippocampal structure may play a role in postpartum cognitive function and mood disorders, as well as age-related cognitive decline.
Assuntos
Envelhecimento/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Hipocampo/fisiologia , Plasticidade Neuronal , Estresse Fisiológico , Animais , Cognição , Feminino , Modelos Animais , Neurogênese , GravidezRESUMO
Stressful life events, especially those that induce fear, can produce a state of anxiety that is useful for avoiding similar fearful and potentially dangerous situations in the future. However, they can also lead to exaggerated states, which over time can produce mental illness. These changing states of readiness versus illness are thought to be regulated, at least in part, by alterations in dendritic and synaptic structure within brain regions known to be involved in anxiety. These regions include the amygdala, hippocampus, and prefrontal cortex. In this article, we review the reciprocal relationships between the expression of stress- and anxiety-related behaviors and stress-induced morphological plasticity as detected by changes in dendrites and spines in these three brain regions. We begin by highlighting the acute and chronic effects of stress on synaptic morphology in each area and describe some of the putative mechanisms that have been implicated in these effects. We then discuss the functional consequences of stress-induced structural plasticity focusing on synaptic plasticity as well as cognitive and emotional behaviors. Finally, we consider how these structural changes may contribute to adaptive behaviors as well as maladaptive responses associated with anxiety.
Assuntos
Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Espinhas Dendríticas/patologia , Plasticidade Neuronal , Estresse Fisiológico , Tonsila do Cerebelo/fisiopatologia , Animais , Encéfalo/patologia , Espinhas Dendríticas/fisiologia , Hipocampo/fisiopatologia , Humanos , Rede Nervosa , Córtex Pré-Frontal/fisiopatologia , Estresse Psicológico/fisiopatologiaAssuntos
Emoções , Inteligência , Relações Pais-Filho , Mulheres , Adulto , Pré-Escolar , Feminino , Humanos , LactenteRESUMO
Dendritic spines in the hippocampus are sources of synaptic contact that may be involved in processes of learning and memory [Moser (1999) Cell. Mol. Life Sci., 55, 593-600]. These structures are sensitive to sex differences as females in proestrus possess a greater density than males and females in other stages of the estrous cycle [Woolley et al. (1990) J. Neurosci., 10, 4035-4039]. Moreover, exposure to an acute stressful event increases spine density in the male hippocampus but decreases spine density in the female hippocampus [Shors et al. (2001) J. Neurosci., 21, 6292-6297]. Here we demonstrate that antagonism of N-methyl-d-aspartate (NMDA) receptors prevents the increase in spine density as females transition from diestrus 2 to proestrus, when estrogen levels are rising. Antagonism of NMDA receptors during exposure to the stressful event also prevented the changes in spine density in males and females, despite differences in the direction of these effects. Thus, the stress-induced increase in spine density was prevented in the male hippocampus as was the stress-induced decrease in spine density in the female hippocampus. NMDA receptor antagonism during exposure to the stressful event did not alter corticosterone levels or the corticosterone response to stress. These data suggest that both increases and decreases in spine density can be dependent on NMDA receptor activation.