No abstract

Stress plays a key role in the induction of various clinical disorders by altering monoaminergic response and antioxidant defenses. In the present study, alterations in the concentrations of dopamine (DA), serotonin (5-HT) and their metabolites, and simultaneous changes in the antioxidant defense system and lipid peroxidation in different brain regions (frontal cortex, striatum, and hippocampus) were investigated immediately and 24 h after exposure to chronic unpredictable stress (CUS). CUS involved subjecting Sprague-Dawley rats to two different types of stressors varying from mild to severe intensity every day in an unpredictable manner, over a period of 7 days. CUS significantly decreased DA and 5-HT concentrations, with increased DA turnover ratios in the selected brain regions. In the frontal cortex and striatum, DA metabolite concentrations were increased; however, in the hippocampus they remained unaltered. Further, a decrease of 5-hydroxyindoleacetic acid content was observed in the frontal cortex and striatum, with no significant alteration in the hippocampus. CUS also reduced the activities of superoxide dismutase and catalase, with increased lipid peroxidation and decreased glutathione levels in the selected brain regions. Glutathione peroxidase activity was increased in the frontal cortex and hippocampus only. The pattern of CUS-induced monoamine and oxidative changes immediately after the last stressor and 24 h later were similar when compared with the control group, indicating that the observed changes were due to the chronic exposure to the various stressors and were not merely acute effects of the last stressor. The altered redox state in the striatum and frontal cortex might be related to the perturbed DA and/or 5HT levels, while the hippocampus seems to be less influenced by CUS in terms of monoamine metabolite changes. These results suggest that the perturbed monoamine levels could interact with the oxidative load during CUS. Hence, the current study has implications for pharmacological interventions targeting both central monoamines and cellular antioxidants as a potential stress management strategy for protecting against central stress-induced disorders.

Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive "reporter cells" that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) and young adult controls (YC). AD is characterized by higher activities of hexokinase, phosphofructokinase, and bisphosphoglycerate mutase and bisphosphoglycerate phosphatase in RBCs. In our study, we observed that glycolytic and related enzymes displayed significantly lower activities in AC. However, similar or significantly higher activities were observed in AD and NA groups as compared to YC group. 2,3-diphosphoglycerate (2,3-DPG) levels were significantly decreased in AD and NA patients. The pattern of changes between groups in the above indices strongly correlates with each other. Collectively, our data suggested that AD and NA patients are associated with chronic disturbance of 2,3-DPG metabolism in RBCs. These defects may play a pivotal role in physiological processes, which predispose elderly subjects to AD and NA.

No abstract

We aimed to evaluate the response of dopaminergic system in acute stress (AS) and chronic unpredictable stress (CUS) by measuring dopamine (DA) levels, its receptor densities in the frontal cortex, striatum, hippocampus, amygdala and orbito-frontal cortex regions of rat brain, and investigated the corresponding behavioral locomotor changes. Involvement of D(1) receptor was also examined during AS and CUS using A 68930, a D(1) selective agonist. Rats were exposed to AS (single immobilization for 150 min) and CUS (two different stressors for 7 days). AS significantly decreased the DA levels in the striatum and hippocampus, and A 68930 pretreatment significantly reverted these changes. However, in the frontal cortex significantly increased DA levels were remain unchanged following A 68930. CUS led to a decrease of DA levels in the frontal cortex, striatum and hippocampus, which were normalized by A 68930. Saturation radioligand binding assays revealed a significant decrease in the number of D(1)-like receptors in the frontal cortex during CUS, which were further decreased by A 68930 pretreatment. However, in the striatum and hippocampus, A 68930 pretreatment reduced the CUS induced increase in the number of D(1)-like receptors. No significant changes were observed in the amygdala and orbito-frontal cortex during AS and CUS, while D(2)-like receptors were unchanged in all the brain regions studied. Locomotor activity was significantly decreased in both the stress models, A 68930 pretreatment significantly increased stereotypic counts and horizontal activity. Thus, present investigation provide insights into the differential regional response of dopaminergic system during AS and CUS. Further, neurochemical and behavioral effects of D(1) agonist pretreatment suggest specific modulatory role of D(1) receptor under such stressful episodes.

Stress is the leading psychopathological cause for several mental disorders. Physiological and psychological responses to stress are mediated by the hypothalamic?pituitary?adrenal (HPA), sympathoadrenal system (SAS), and brain monoaminergic systems (BMS). Eugenol is reported to substantially modulate brain functions by regulating voltage-gated cation channels and release of neurotransmitters. This study was designed to evaluate the anti-stress effect of eugenol in the 4-h restraint model using rats. Ulcer index was measured as a parameter of the stress response. HPA axis and the SAS were monitored by estimating plasma corticosterone and norepinephrine (NE), respectively. Analysis of NE, serotonin (5-HT), dopamine, and their metabolites in discrete brain regions was performed to understand the role of BMS in the anti-stress effect of eugenol. Stress exposure increased the ulcer index as well as plasma corticosterone and NE levels. Eugenol pretreatment for 7 days decreased the stress-induced increase in ulcer index and plasma corticosterone but not NE levels, indicating a preferential effect on the HPA axis. Furthermore, eugenol showed a ?U?-shaped dose?response curve in decreasing ulcer index and plasma corticosterone levels. Eugenol also reversed the stress-induced changes in 5-HT levels in all brain regions, whereas NE levels were reversed in all brain regions except hippocampus. These results suggest that eugenol possesses significant anti-stress activity in the 4-h restraint model and the effect is due to modulation of HPA and BMS.

No abstract

The two most common forms of dementia are Alzheimer's disease (AD) followed by vascular dementia (VaD), together accounting for a whopping 60-80% of total dementia cases worldwide. Even though these diseases are recognized as 'common', they still remain underdiagnosed. Recent research suggests that AD and VaD are closely intertwined. The symptoms of AD and VaD can be similar and the two conditions can occur simultaneously. A large number of patients diagnosed with AD have also been reported with VaD-caused brain damage. Moreover, both the diseases have been reported to have similar risk factors. The overlap between these diseases is important because the lifestyle changes and medications prescribed to curb one of these diseases may also help curb the other. In the present review, we present an inclusive outline of parallelism between AD and VaD by exploring the potential commonalities at the mechanistic and therapeutic levels.