Mapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression.
ABSTRACT Antidepressant drugs as well as electroconvulsive stimuli can significantly influence brain concentrations of neurotrophic factors. However, it is not known whether the baseline brain concentrations of neurotrophic factors are altered in human subjects suffering from affective disorders or whether there are sex differences in concentrations of neurotrophins in human brain. In order to elucidate some of these questions, we measured by ELISA brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression, the Flinders Sensitive Line (FSL) rats and their controls, the Flinders Resistant Line (FRL). Altered BDNF and NGF concentrations were found in frontal cortex, occipital cortex, and hypothalamus of depressed FSL compared to FRL control rats. Furthermore, different levels of these neurotrophins were also found in the male and female brain. Cumulatively these observations suggest that BDNF and NGF may play a role in depression and, hypothetically, different brain regional concentrations of BDNF and NGF in male and female animals may be relevant to gender differences in vulnerability to depression.
- SourceAvailable from: Serkan Zincir
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- "There are few studies in the literature about NGF levels in major depression and its exchange with treatment, and animal studies often provide contradictory results. (Reus et al., 2011; Schulte-Herbruggen et al., 2009; Angelucci et al., 2000; Martino et al., 2013; Xiong et al., 2011). "
ABSTRACT: This study aimed to investigate the effects of electroconvulsive treatment on serum BDNF and NGF levels in patients with treatment-resistant major depression. Thirty patients with treatment-resistant major depression and 30 healthy controls were included in the study. The patients' serum BDNF and NGF levels were measured three times; before treatment (T0), when the clinical response occurred (T1) and at the end of treatment (T2). The reduction detected in the HAM-D scores with ECT during the T0-T1, T1-T2 and T0-T2 periods was found to be statistically significant. In the patient group, increase in the mean BDNF levels after ECT treatment was found to be statistically significant (p<0.05). Significant increases in serum BDNF levels with ECT were lower than in the control group, and the serum NGF levels did not increase significantly. There was no relationship between the severity of the depression and serum BDNF and NGF levels (p>0.05). This study evaluated the role of neurotrophic factors in the etiopathogenesis of major depression. Future studies should investigate the relationship between neurotrophic factors with neuroendocrine and genetic processes to elucidate the psychobiology and treatment of mental disorders.Brain research bulletin 04/2014; DOI:10.1016/j.brainresbull.2014.04.005 · 2.97 Impact Factor
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- "In our study, we looked at protein levels, indicating that the lower BDNF levels observed here probably reflect differences in posttranslational processing or turnover rate in the cLH animals. Reduced levels of BDNF protein are also observed in several brain regions of Flinders Sensitive Line (Angelucci et al., 2000) and, similar to cLH rats, there is an absence of stress-induced regulation of BDNF expression in the hippocampus of Flinders Sensitive Line when compared with Sprague–Dawley and Flinders Resistant Line. We cannot exclude an exacerbated age-dependent decrease in BDNF levels specific for the CA1 area in the cLH rats, which may have been overseen as we only measured BDNF levels in total hippocampal lysates. "
ABSTRACT: Epidemiological studies have revealed a strong genetic contribution to the risk for depression. Both reduced hippocampal serotonin neurotransmission and brain-derived neurotrophic factor (BDNF) levels have been associated with increased depression vulnerability and are also regulated during aging. Brains from young (5 months old) and old (13 months old) congenital Learned Helplessness rats (cLH), and congenital Non Learned Helplessness rats (cNLH) were immunohistochemically stained for the serotonin transporter and subsequently stereologically quantified for estimating hippocampal serotonin fiber density. Hippocampal BDNF protein levels were measured by ELISA. An exacerbated age-related loss of serotonin fiber density specific for the CA1 area was observed in the cLH animals, whereas reduced hippocampal BDNF levels were seen in young and old cLH when compared with age-matched cNLH controls. These observations indicate that aging should be taken into account when studying the neurobiological factors behind the vulnerability for depression and that understanding the effect of aging on genetically predisposed individuals may contribute to a better understanding of the pathophysiology behind depression, particularly in the elderly.Synapse 07/2010; 64(7):561-5. DOI:10.1002/syn.20773 · 2.43 Impact Factor
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- "Chronic instead of (sub)-acute treatment with different antidepressant agents, established or still experimental, followed by a 24-h wash-out period, successfully reverses such 'depressive'-like behaviour in male FSL rats in this modified single session FST protocol (Overstreet, 2002; Overstreet, et al., 2004; Zangen, et al., 1997, 1999). However, relatively few studies (Angelucci, et al., 2000; Djuric, et al., 1999; Jimenez-Vasquez, et al., 2000; Lavi- Avnon, et al., 2005a,b) have used female FSL rats and evidence so far suggests that in this modified single session FST paradigm , female FSL rats do not present a clear 'depressive'-like behavioural profile as males do. However, to our knowledge, no study has focused on the impact of any antidepressant treatment on female FSL rats using the FST or any other relevant behavioural paradigm. "
ABSTRACT: Research in affective disorders is often performed without considering sex differences, although women are predominantly affected. Consequently, the potential sex-dependent action of antidepressants remains elusive. We investigated whether Flinders sensitive line (FSL) of rats, a model of depression, would present sex-differentiated responses to antidepressant treatment. FSL and Sprague-Dawley rats were treated with clomipramine 10 mg/kg/day for 14 days. Subsequently, they were subjected to either a single session of the forced swim test or an estimation of serotonergic function in the prefrontal cortex, hippocampus, amygdala and hypothalamus. Male FSL displayed increased immobility duration, decreased active behaviours, increased serotonin tissue levels and a reduced serotonin turnover rate in most brain areas studied. Female FSL showed a distinct profile, consisting of decreased immobility latency, increased climbing duration, limited serotonergic deviations and no difference in the serotonin turnover rate in comparison with controls. Interestingly, despite baseline differences, clomipramine treatment reversed all relevant behavioural responses and increased the serotonin turnover rate in both sexes. However, the latter effect was remarkably more pronounced in females. It is concluded that, in this animal model of depression, chronic clomipramine treatment attenuated baseline sex differences in the phenotype while maintaining or intensifying the sex differentiation in the serotonergic endophenotype.Journal of Psychopharmacology 09/2008; 23(8):945-56. DOI:10.1177/0269881108095914 · 2.81 Impact Factor