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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute stress has been known to produce several behavioral, neurochemical and biochemical alterations. Cyclooxygenase (COX) enzymes are involved in pathogenesis of several brain disorders including Alzheimer disease, epilepsy, depression, in addition to pain and inflammation. In the present study, we examined the role of non-selective (naproxen) and selective (rofecoxib, valdecoxib) COX-2 inhibitors against acute immobilization stress-induced behavioral alterations and oxidative damage in mice. Mice were subjected to acute immobilization stress for a period of 6 h. Naproxen (7 and 14 mg/kg, ip), rofecoxib (5 and 10 mg/kg, ip) or valdecoxib (5 and 10 mg/kg, ip) were administered 30 min before acute stress. Six-our immobilization stress significantly caused anxiety-like behavior, memory deficit and impaired motor activity as well as oxidative damage (raised lipid peroxidation, nitrite activity, depletion of reduced glutathione and catalase activity) as compared to naive animals placed on sawdust (p < 0.05). Pretreatment with naproxen (7 and 14 mg/kg, ip), rofecoxib (5 and 10 mg/kg, ip) and valdecoxib (5 and 10 mg/kg, ip) significantly improved locomotor activity, antianxiety effect, memory retention (memory deficit) and attenuated oxidative damage (lowering of raised malondialdehyde, nitrite activity, restoration of reduced glutathione and catalase activity as compared to immobilization stress group (p < 0.05). Results suggest the neuroprotective and antioxidant effect of both non-selective and selective COX-2 inhibitors.
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PMID:Protective effect of non-selective and selective COX-2-inhibitors in acute immobilization stress-induced behavioral and biochemical alterations. 1819 59

The signaling adapter p62 plays a coordinating role in mediating phosphorylation and ubiquitin-dependent trafficking of interacting proteins. However, there is little known about the physiologic role of this protein in brain. Here, we report age-dependent constitutive activation of glycogen synthase kinase 3beta, protein kinase B, mitogen-activated protein kinase, and c-Jun-N-terminal kinase in adult p62(-/-) mice resulting in hyperphosphorylated tau, neurofibrillary tangles, and neurodegeneration. Biochemical fractionation of p62(-/-) brain led to recovery of aggregated K63-ubiquitinated tau. Loss of p62 was manifested by increased anxiety, depression, loss of working memory, and reduced serum brain-derived neurotrophic factor levels. Our findings reveal a novel role for p62 as a chaperone that regulates tau solubility thereby preventing tau aggregation. This study provides a clear demonstration of an Alzheimer-like phenotype in a mouse model in the absence of expression of human genes carrying mutations in amyloid-beta protein precursor, presenilin, or tau. Thus, these findings provide new insight into manifestation of sporadic Alzheimer disease and the impact of obesity.
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PMID:Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and neurodegeneration. 1834 6

The prevalence of Alzheimer disease is higher in women than in men. In the age group 65-69 years 0.7% of women and 0.6% of men suffer from the disease with increasing frequencies of 14.2% and 8.8% in individuals aged 85-89 years. The incidence is also higher in demented women. In Austria 74.1% of Alzheimer patients older than 60 years are women. Several studies report more pronounced language, mnestic, semantic and orientation deficits in women, but methodological shortcomings might be responsible for this finding. The validity of results reporting a more rapid cognitive decline in women can also be questioned. Women have a broader spectrum of dementiarelated behavioural symptoms with a predominance of depression, while aggression is more frequent in men than in women. Biological explanations for gender-specific differences in the phenotype of Alzheimer s disease include different brain morphology and function with higher susceptibility for pathological lesions in women and greater cognitive reserve in men. Sex differences were also reported for expression of antioxidative enzymes and post-menopausal hormonal changes. Interactions between gender nd response to treatment, if any, are subtle and have large intra-individual variability. In Austria, two thirds of patients receiving attendance allowance are women. Care takes place in 80% by the families and is provided by women in 78%. The rate of female care-givers in partly institutionalized care units in 91% in nursing homes it is 84%.
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PMID:[Sex differences in Alzheimer's disease]. 1838 Oct 51

Cross-sectional and longitudinal analyses were carried out to assess the relationship between dementia patient suffering, caregiver depression, and antidepressant medication use in 1222 dementia patients and their caregivers. We assessed the prevalence of 2 types of patient suffering, emotional and existential distress, and examined their independent associations with caregiver depression and antidepressant medication use when controlling for sociodemographic characteristics of caregivers and patients, cognitive and physical disability of the patient, the frequency of patient memory problems and disruptive behaviors, and the amount of time spent caring for the patient. Multiple linear regression models showed that both aspects of perceived patient suffering independently contribute to caregiver depression (emotional distress: beta=1.24; P<0.001; existential distress: beta=0.66; P<0.01) whereas only existential suffering contributes to antidepressant medication use: odds ratio=1.25 95% confidence interval, 1.10-1.42; P<0.01. In longitudinal analyses, increases in both types of suffering were associated with increases in caregiver depression (emotional distress: beta=1.02; P<0.01; existential distress: beta=0.64; P<0.01). This is the first study to show in a large sample that perceived patient suffering independently contributes to family caregiver depression and medication use. Medical treatment of patients that maintain or improve memory but do not address suffering may have little impact on the caregiver. Alzheimer disease patient suffering should be systematically assessed and treated by clinicians.
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PMID:Dementia patient suffering and caregiver depression. 1852 90

Alzheimer's disease constitutes a rising threat to public health. Despite extensive research in cellular and animal models, identifying the pathogenic agent present in the human brain and showing that it confers key features of Alzheimer's disease has not been achieved. We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease. The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. Soluble Abeta from Alzheimer's disease brain also disrupted the memory of a learned behavior in normal rats. These various effects were specifically attributable to Abeta dimers. Mechanistically, metabotropic glutamate receptors were required for the LTD enhancement, and N-methyl D-aspartate receptors were required for the spine loss. Co-administering antibodies to the Abeta N-terminus prevented the LTP and LTD deficits, whereas antibodies to the midregion or C-terminus were less effective. Insoluble amyloid plaque cores from Alzheimer's disease cortex did not impair LTP unless they were first solubilized to release Abeta dimers, suggesting that plaque cores are largely inactive but sequester Abeta dimers that are synaptotoxic. We conclude that soluble Abeta oligomers extracted from Alzheimer's disease brains potently impair synapse structure and function and that dimers are the smallest synaptotoxic species.
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PMID:Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. 1856 35

Dehydroepiandrosterone (DHEA) and its sulfate metabolite (DHEAS) are the major androgens secreted by the human adrenal gland. The decline in their production is the most characteristic age-related change in the adrenal cortex. This process, known as 'adrenopause' may contribute to the increased incidence of atherosclerosis, cancer, or dementia in older people. The possibility of using DHEA in management has attracted considerable attention over recent years. Whereas DHEA therapy seems to be effective in treating patients with adrenal insufficiency and systemic lupus erythematosus, clinical studies investigating the potential efficacy of DHEA therapy in multiple other disorders (Alzheimer disease, depression, cardiovascular disease, osteoporosis, sexual dysfunctions) have not provided consistent results. Further research is also needed to better assess the efficacy and safety of DHEA supplementation in patients with advanced age. This review evaluates current understanding of physiology and pathology of DHEA production and summarizes the possible therapeutic value of this hormone.
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PMID:[Current views on the role of dehydroepiandrosterone in physiology, pathology and therapy]. 1863 57

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurological disorder that affects older adult carriers, predominantly males, of premutation alleles (55 to 200 CGG repeats) of the fragile X (FMR1) gene. Principal features of FXTAS are intention tremor, ataxia, parkinsonism, cognitive decline, and peripheral neuropathy; ancillary features include, autonomic dysfunction, and psychiatric symptoms of anxiety, depression, and disinhibition. Although controlled trials have not been carried out in individuals with FXTAS, there is a significant amount of anecdotal information regarding various treatment modalities. Moreover, there exists a great deal of evidence regarding the efficacy of various medications for treatment of other disorders (eg, Alzheimer disease) that have substantial phenotypic overlap with FXTAS. The current review summarizes what is currently known regarding the symptomatic treatment, or potential for treatment, of FXTAS.
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PMID:Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. 1868 48

Psychotropic drugs acting on monoamine neurotransmission are major pharmacological treatments for neuropsychiatric conditions such as schizophrenia, depression, bipolar disorder, Tourette syndrome, ADHD, and Alzheimer disease. Independent lines of research involving biochemical and behavioral approaches in normal and/or genetically modified mice provide converging evidence for an involvement of the signaling molecules Akt and glycogen synthase kinase-3 (GSK3) in the regulation of behavior by dopamine and serotonin (5-HT). These signaling molecules have also received attention for their role in the actions of psychoactive drugs such as antidepressants, antipsychotics, lithium, and other mood stabilizers. Furthermore, investigations of the mechanism by which D2 dopamine receptors regulate Akt/GSK3 signaling strongly support the physiological relevance of a new modality of G protein-coupled receptor (GPCR) signaling involving the multifunctional scaffolding protein beta-arrestin 2. Elucidation of the contribution of multiple signaling pathways to the action of psychotropic drugs may provide a better biological understanding of psychiatric disorders and lead to more efficient therapeutics.
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PMID:Akt/GSK3 signaling in the action of psychotropic drugs. 1892 2

Depression is common in patients with neurologic disorders such as Alzheimer disease, stroke, Parkinson disease, and multiple sclerosis. Diagnosing depression in the context of neurologic disease is challenging, given the overlap between many signs and symptoms of depression with those of the neurologic disorders. Cognitive impairment further complicates diagnostic evaluation. The etiology of depression in these patients is not well understood and variously has been attributed to emotional reaction to the diagnosis or disability associated with the neurologic condition, the anatomical and/or neurochemical outcomes of neurodegeneration, and the influence of other disease factors. Beyond the inherent burden depression places on patients and caregivers, it increases cognitive and functional disability and, depending on the neurologic disorder, poorer treatment adherence and recovery, earlier institutionalization, and increased suicide risk. Few controlled antidepressant trials are available to guide treatment. In the absence of validated diagnostic guidelines for depression in each neurologic condition, clinicians are urged to remain vigilant for this treatable comorbidity. Although more controlled trials clearly are needed, existing studies suggest that depression in patients with neurologic disorders responds to antidepressant medication and, in some disorders, to psychotherapeutic approaches. Investigating the neuroanatomical and neurochemical correlates of depression comorbid with neurologic conditions also may clarify depression etiology and treatment in the general population.
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PMID:Diagnosis and treatment of depression comorbid with neurologic disorders. 1895 90

Abnormal protein phosphorylation has been associated with several neurodegenerative disorders, including Alzheimer's disease (AD). Abeta is the toxic peptide that results from proteolytic cleavage of the Alzheimer's amyloid precursor protein, a process where protein phosphatases are known to impact. The data presented here demonstrates that protein phosphatase 1 (PP1), an abundant neuronal serine/threonine-specific phosphatase highly enriched in dendritic spines, is specifically inhibited by Abeta peptides both in vitro and ex vivo. Indeed, the pathologically relevant Abeta(1-40) and Abeta(1-42) peptides, as well as Abeta(25-35), specifically inhibit PP1 with low micromolar potency, as compared to inactive controls and other disease related peptides (e.g. the prion related Pr(118-135) and Pr(106-126)). Interestingly, PP1 inhibition is increased by Abeta aggregation, indicating a possible direct neurotoxic effect of the aggregated peptide. PP1 involvement in processes like long-term depression, memory and learning, and synaptic plasticity, prompt us to suggest that PP1 may constitute an important physiological target for Abeta and, therefore, increased Abeta production and/or aggregation may lead to abnormal PP1 activity and likely contribute to the progressive neuropsychiatric AD condition. Thus, PP1 activity and levels constitute potential biomolecular candidates for diagnostics and therapeutics.
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PMID:PP1 inhibition by Abeta peptide as a potential pathological mechanism in Alzheimer's disease. 1902 67


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