Long-term pretreatment with an angiotensin II AT1 antagonist blocks angiotensin II effects in brain and peripheral organs and abolishes the sympathoadrenal and hypothalamic-pituitary-adrenal responses to isolation stress. We determined whether AT1 receptors were also important for the stress response of higher regulatory centers. We studied angiotensin II and corticotropin-releasing factor (CRF) receptors and benzodiazepine binding sites in brains of Wistar Hannover rats.
View Article and Find Full Text PDFThe brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT(1) antagonist candesartan blocks not only peripheral but also brain AT(1) receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers.
View Article and Find Full Text PDFIn transgenic mice expressing an antisense mRNA against the glucocorticoid receptor (GR), which partially blocks GR expression, impaired glucocorticoid feedback efficacy is accompanied by reduced hypothalamic corticotropin-releasing hormone (CRH) and vasopressin (AVP) activity and reduced peripheral sympathetic tone, indications of a shift in the balance of hypothalamic CRH and sympathetic regulation. As angiotensin II (Ang II) regulates CRH, AVP and sympathetic activity, we studied the expression of Ang II receptors in the hypothalamus and adrenal gland of GR transgenic and wild-type mice, adrenal catecholamines and mRNA for their rate-limiting enzyme, tyrosine hydroxylase (TH). We found that transgenic mice expressed significantly less numbers of Ang II AT(1) receptors in the hypothalamic paraventricular nucleus and median eminence, lower numbers of AT(2) receptors in supraoptic and paraventricular nuclei and lower numbers of AT(2) receptors in the adrenal medulla when compared with wild-type controls.
View Article and Find Full Text PDFIncreasing evidence suggests that schizophrenia is a neurodevelopmental disorder with a progressive course characterized by worsening of symptoms and morphological alterations within the brain. This suggests that a neurodegenerative component may exist in schizophrenia. The role of brain-derived neurotrophic factor (BDNF) in neurodevelopment, cell viability and synaptic plasticity led to the investigation of BDNF as a potential candidate molecule in the pathophysiology of schizophrenia.
View Article and Find Full Text PDFApart from their differential propensities to block dopamine D2 and serotonin 5-HT2 receptors, the molecular mechanisms underlying the clinical efficacy of typical and atypical antipsychotics in schizophrenia are largely unknown. Given recent interest in the effects of antipsychotics on neurotrophic and other growth related factors, the effects of antipsychotics on brain-derived neurotrophic factor (BDNF), a neurotrophin crucial to the structural integrity of adult neurons, were investigated in male Wistar rats. Chronic (19 day) but not acute (45 min) antipsychotic administration significantly altered levels of hippocampal BDNF mRNA.
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