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ABSTRACT: Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress.
PLoS ONE 01/2011; 6(9):e24263. · 4.09 Impact Factor
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ABSTRACT: Corticosterone inhibits male rodent sexual behavior while the mechanism remains obscured. Recent studies have disclosed that neurogenesis in the subventricular zone (SVZ) can be increased by pheromone exposure from the opposite sex, and neurogenesis is essential for normal mating behavior of female mice. Together with the neurogenesis-inhibiting effect of corticosterone, we hypothesize that cell proliferation in the olfactory system is essential for male rodent sexual functioning.
The current study explored the relationship between cell proliferation in the olfactory system and male sexual behavior.
Sexual behavior performance, proliferative cell counts, and c-fos-expressing cell counts.
Adult male rats were treated with corticosterone and/or paroxetine, an antidepressant, for 2 weeks. These two drugs were shown to suppress and enhance hippocampus and SVZ cell proliferation, respectively. Mating behavior was assessed after the treatment, and proliferation of new cells and c-fos-expressing cells, activated neurons in the mating-related regions in the brain, were analyzed. To further confirm the necessity of cell proliferation in mating, inhibition of cell proliferation was performed by intracerebroventricular infusion of cytostatic cytosine arabinose (Ara-c).
Corticosterone treatment, which inhibited cell proliferation in both the SVZ and olfactory epithelium, led to inhibited male sexual performance. In contrast, paroxetine increased cell proliferation and improved the performance in corticosterone-treated animals. When cell proliferation in the brain was inhibited by Ara-c, a suppressed sexual performance was found. However, cell proliferation in olfactory epithelium was not inhibited by Ara-c and thus the sexual inhibition is unlikely to be linked to this region. Furthermore, a decrease in c-fos expression in the mating-related regions upon female pheromone stimulation was found.
These results suggest that cell proliferation in the SVZ and hippocampus may be involved in the reproduction of the male rodents, and pharmacological treatments may affect sexual functioning through alteration of neurogenesis.
Journal of Sexual Medicine 10/2010; 8(5):1390-403. · 3.55 Impact Factor
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ABSTRACT: The neurogenesis in retina of adult mammals is generally abolished, and this renders the retina lack of regenerative capacity. Despite this, there is a small population of nestin-positive cells in the ciliary epithelium which retains neurogenic potential. The present study aimed at investigating the effect of two drugs, corticosterone and paroxetine, on the cell proliferation of the ciliary body.
Adult Sprague-Dawley rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine treatment for 14 days. Cell proliferation in the ciliary body was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry. Co-labelling of BrdU and stem cell marker was used to phenotype the BrdU immunoreactive cells.
Corticosterone treatment suppressed while paroxetine treatment increased the cell proliferation of the ciliary body. Co-labelling with cell markers revealed that the BrdU positive cells also showed nestin expression but not glial fibrillary acidic protein (GFAP).
The results illustrate that proliferation of retinal progenitor cells situated in ciliary body are subjected to regulation by selective serotonin reuptake inhibitors (SSRI) and corticosteroid, which is similar to our previous findings in neurogenic regions in central nervous system (CNS). Paroxetine treatment could reverse the suppressive effect of corticosterone on ciliary body cell proliferation. This provides information for future investigation of retinal stem cell biology and potential treatment of retinal degenerative diseases.
Chinese medical journal 05/2010; 123(10):1305-10. · 0.86 Impact Factor
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ABSTRACT: This paper is a report of a study to identify the changes in poststroke quality of life and other clinical issues among older Chinese adults from 1 month to 6 months after stroke and the predictors of poststroke quality of life at 6 months.
Stroke survivors are known to suffer from prolonged and multiple impairments leading to a compromised quality of life, but few studies report early predictors for quality of life among older Chinese adults after active rehabilitation has been undertaken during the first 6 months after stroke.
A total of 214 patients with first-ever ischaemic stroke were interviewed by a research nurse at 1 month and 188 patients were interviewed again 6 months after hospital admission for stroke. Assessment of quality of life was done using the Modified Rankin Scale for Quality of Life. Changes in and relationships between quality of life and variables in five domains were explored: bio-anatomical, physical, emotional, cognitive, communicative and social support. The data were collected in 2004-2005.
Quality of life among two-thirds of participants was unchanged or lower when scores at 1 month and 6 months after stroke were compared. Length of hospital stay after admission for stroke and other 1-month factors - level of worry over current health, cognitive and self-care deficits - were identified as having independent effects on quality of life at 6 months.
Clinicians need to observe for early signs of mild cognitive impairments and emotional needs of stroke survivors, as well as to consider longer-term interventions to enhance poststroke quality of life.
Journal of Advanced Nursing 04/2009; 65(3):554-64. · 1.48 Impact Factor
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ABSTRACT: Adult neurogenesis in hippocampus is associated with behaviors such as learning. Hippocampus is involved in the regulation of prepulse inhibition (PPI), but the relationship between neurogenesis and PPI is unexplored. We conducted four experiments to determine the role of neural progenitor cell proliferation in PPI. Intracerebroventricular infusion of cytostatic cytosine arabinoside caused PPI disruption but repeated exposure to PPI sessions prevented the PPI disruption. Corticosterone treatment, which decreases hippocampal cell proliferation, caused PPI disruption, whereas antidepressant and exercise, which increased cell proliferation, did not affect PPI. These results suggest that cell proliferation is involved in the first encounter with PPI test while its importance may decrease upon repeated exposures to the tests.
Neuroreport 03/2009; 20(4):371-7. · 1.66 Impact Factor
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ABSTRACT: Paroxetine is a widely used antidepressant that has received attention regarding suicide risk in younger patients.
The purpose of this paper is to review the pharmacology, efficacy and safety of paroxetine in the affective disorders.
The authors performed a PubMed search for all literature in English crossing the words 'paroxetine' and 'Paxil' against the words 'serotonin transporter,' 'clinical trials,' 'depression' and 'SSRI'. A search for paroxetine-related information at the FDA website and under the clinical trial register of the GSK website were also performed.
Paroxetine is a serotonin re-uptake inhibitor with good selectivity and no significant active metabolites. Paroxetine is approved (ages >or= 18 years) for the treatment of major depressive disorder, panic disorder, obsessive-compulsive disorder, social anxiety disorder (social phobia), post-traumatic stress disorder, and generalized anxiety disorders. Drug - drug interactions involving the CYP enzyme system have been documented, as well as concern for increased suicidality risk in younger adults and recent FDA alerts regarding teratogenicity, serotonin syndrome and persistent pulmonary hypertension.
Expert Opinion on Pharmacotherapy 04/2008; 9(5):787-94. · 3.20 Impact Factor
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ABSTRACT: The effect of short-term exercise (15 min step-exercise) on serum brain-derived neurotrophic factor (BDNF) levels was evaluated in healthy human subjects. Results showed a short-term, significant increase in serum BDNF levels after exercise. Intra-individual differences in serum BDNF levels were remarkably small on the rest day and also when compared to rest values on the day of the exercise test. Inter-individual differences, on the other hand, were larger by comparison. The result of this study supports the need for larger sample size in studies on BDNF changes in psychiatric disorders or psychiatric drug effects.
Neuroscience Letters 02/2008; 431(1):62-5. · 2.11 Impact Factor
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ABSTRACT: The literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study.
Adult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine (BrdU) immunohistochemistry.
The corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation.
This may have clinic application in preventing hippocampal damage after glucocorticoid treatment.
Neuroscience Bulletin 06/2007; 23(3):131-6. · 1.31 Impact Factor
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ABSTRACT: Major depressive disorder is often associated with elevated glucocorticoid levels, which in turn suppress cell proliferation and neurogenesis in the hippocampus. Increasing evidence supports that antidepressants induce hippocampal neurogenesis and this induces speculation that decrease in hippocampal neurogenesis has causal relationship with depression. There is, however, a lack of information about neurogenic effects of antidepressants on the subventricular zone, which is another CNS region with continuous neurogenesis throughout adulthood. In the present study, we investigated whether corticosterone and the SSRI paroxetine, have effects on SVZ cell proliferation.
Rats were treated with the corresponding drugs for 14 days and the proliferating cells were labeled with bromodeoxyuridine (BrdU). BrdU labeled cells in the SVZ were quantified and analyzed.
In the corticosterone-treatment group, cell proliferation was decreased by 18% compared to vehicle-treatment group. Paroxetine-treatment group, in contrast, shows a 34% increase in cell proliferation. The decreased cell proliferation caused by corticosterone was prevented by paroxetine.
Although corticosterone and antidepressants were found to affect cell proliferation in hippocampus, this is the first report to demonstrate that 1) corticosterone decreases cell proliferation in SVZ; 2) paroxetine promotes SVZ cell proliferation and 3) the suppressive effect on SVZ cell proliferation by corticosterone could be attenuated by paroxetine. These findings provide new insights into basic mechanisms of antidepressants, potential impact of steroid therapy on CNS neurogenesis, antidepressant mechanisms of action and potential involvement of the olfactory system in depression.
Restorative neurology and neuroscience 02/2007; 25(1):17-23. · 2.51 Impact Factor
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ABSTRACT: The mental health of tertiary education students is an area of increasing concern worldwide. The objective of this study is to examine the prevalence of depression, anxiety and stress in first-year tertiary education students in Hong Kong.
Depression, anxiety and stress were measured by the 42-item Depression Anxiety Stress Scales, completed on the web by participating students anonymously.
A total of 7915 students completed the survey, yielding a response rate of 27.5%. Depression, anxiety and stress levels of moderate severity or above were found in 21%, 41% and 27% of our respondents, respectively.
The web-based survey methodology was well accepted by our sample group of tertiary education students. We found high rates of psychological morbidity in first-year tertiary education students in Hong Kong. The high prevalence of depression, anxiety and stress symptoms in the first year of college life is alarming. It illustrates the need for primary and secondary prevention measures, with development of adequate and appropriate support services for this group.
Australian and New Zealand Journal of Psychiatry 10/2006; 40(9):777-82. · 2.93 Impact Factor
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ABSTRACT: There has been much discussion in Japan regarding the reduction of psychiatric beds. For effective healthcare planning, reliable forecasting is important. The purpose of this study was to predict the number of future schizophrenic inpatients using quantitative methodology. Data was obtained from a survey of schizophrenic inpatients conducted annually at the end of March by the Niigata Prefecture from 1974 to 2003. The numbers of schizophrenic inpatients in different age groups over a long period of time were used in a precise time-series analysis to establish trends. Then these past trends were used to forecast inpatient numbers for future years. The pattern of ascents and declines of each inpatient group stratified by age appeared to be duplicated by the next older age group 10 years later. The numbers of inpatients with schizophrenia in 2013 and 2023 are projected to be 78.5% and 56.7% of the number of patients in 2003, respectively. By 2033, the number is forecast to decline to 41.0% of the number in 2003. This study forecasts that inpatients with schizophrenia will decrease substantially over the next several decades. Policy should be designed to reflect this trend.
Psychiatry and Clinical Neurosciences 11/2004; 58(5):573-8. · 2.13 Impact Factor
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ABSTRACT: Calf brain and human platelet extracts purified by Bio-Gel P2 column chromatography contained substances that inhibited serotonin uptake and 3H-imipramine binding. Some of these endogenous substances were also recognized by rabbit antibodies produced against imipramine. The data suggest the possible existence of endogenous serotonin uptake modulators, which may possess a partial molecular structure similar to that identified by the antibodies.
Psychiatry Research.
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ABSTRACT: Inhibition of high-affinity [3H]-imipramine binding to platelet membranes by human plasma fractions and isolated plasma proteins was investigated. Several plasma proteins were found to contribute to the observed apparent inhibition and this contribution was assessed in terms of inhibitor units. Alpha1 acid glycoprotein, high density and low density lipoprotein, IgG and α1-antitrypsin were identified as effective non-specific inhibitors. Alpha-1-acid glycoprotein was confirmed to be the most potent plasma protein inhibitor. Cohn fractions were evaluated for the presence of the postulated endocoid of [3H]-imipramine binding site.
Life Sciences.
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ABSTRACT: The present study investigated the 2-week prevalence of depressive symptoms in college freshmen from Beijing and Hong Kong. The relationship between depression and 3 personality factors in these college freshmen was analyzed.
Center for Epidemiologic Studies Depression Scale (CES-D), Eysenck Personality Questionnaire-Neuroticism, Rosenberg Self-esteem Scale, and Frost Multidimensional Perfectionism Scale were administered to 988 Beijing and 802 Hong Kong Chinese college freshmen.
Approximately 24.8% of freshmen in Beijing had scores on the CES-D exceeding 16, whereas 8.9% reported scores of 25 or higher. There was no sex difference in prevalence in Beijing. Approximately 43.9% of freshmen in Hong Kong had scores on the CES-D exceeding 16, whereas 17.6% reported scores of 25 or higher. The prevalence is significantly different between sexes in Hong Kong, with approximately 36.1% of men having scores of 16 or higher and 13.4% having scores of 25 or higher and approximately 50.7% of women having scores of 16 or higher and 21.3% having scores of 25 or higher. High neuroticism, concern over mistakes, doubts about actions, low self-esteem, and poor organization were associated with current depressive symptoms in both sites.
The higher prevalence of current depressive symptoms in college freshmen in Hong Kong suggests that their mental health is not as satisfactory as that of their counterparts in Beijing. The strong relationship between certain personality features and current depressive symptoms is similar in both regions. Personality differences in the 2 sites explain only part, but not all, of the difference in depressive symptoms between the 2 sites.
Comprehensive psychiatry 49(5):496-502. · 2.08 Impact Factor
