The Experts below are selected from a list of 7173 Experts worldwide ranked by ideXlab platform
Monika Sadananda - One of the best experts on this subject based on the ideXlab platform.
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immediate and delayed anxiety and Depression like profiles in the adolescent wistar kyoto rat model of Endogenous Depression following postweaning social isolation
Behavioural Brain Research, 2017Co-Authors: Reshma A Shetty, Monika SadanandaAbstract:In order to understand links that exist between inherited risk or predisposition, brain and behavioural development, endocrine regulation and social/environmental stimuli, animal models are crucial. The Wistar-Kyoto (WKY) rat has been shown to have validity as a model of adult and adolescent Depression. While sex- and age-specific differences in some of the face, predictive and construct validities of the model such as Depression-like behaviours have been established, anhedonia and anxiety using other induced anxiety paradigms such as elevated plus maze remain equivocal. First, post-weaning social isolation effects on inherent and induced anxiety behaviours were tested during two critical time periods, early- and mid-adolescence. Isolation induced immediate effects on novel environment-induced hyperactivity and anxiety-related behaviours. Adolescent WKYs demonstrated reduced 50-kHz ultrasonic vocalizations suggesting agoraphobia-like behaviours. Second, isolated rats, despite being subsequently social-/group-housed demonstrated longer lasting effects on social interaction measures and anhedonia. This establishes that the Depression-like profile observed during early- and mid-adolescence persists into late adolescence and early adulthood in WKY. Further, that interventions at a later stage during adolescence may not be able to reverse early adolescent effects in the context of pre-disposition, thus highlighting the irreversibility of being double-hit during critical time periods of brain and behavioural development and maturation.
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brief social isolation in the adolescent wistar kyoto rat model of Endogenous Depression alters corticosterone and regional monoamine concentrations
Neurochemical Research, 2017Co-Authors: Reshma A Shetty, Monika SadanandaAbstract:The Wistar-Kyoto rat (WKY) model has been suggested as a model of adult and adolescent Depression though face, predictive and construct validities of the model to Depression remain equivocal. The suitability of the WKY as a diathesis model that tests the double-hit hypothesis, particularly during critical periods of brain and behavioural development remains to be established. Here, effects of post-weaning social isolation were assessed during early adolescence (~30pnd) on behavioural despair and learned helplessness in the forced swim test (FST), plasma corticosterone levels and tissue monoamine concentrations in brain areas critically involved in Depression, such as prefrontal cortex, nucleus accumbens, striatum and hippocampus. Significantly increased immobility in the FST was observed in socially-isolated, adolescent WKY with a concomitant increase in corticosterone levels over and above the FST-induced stress. WKY also demonstrated a significantly increased release and utilization of dopamine, as manifested by levels of metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in nucleus accumbens, indicating that the large dopamine storage pool evident during adolescence induces greater dopamine release when stimulated. The serotonin metabolite 5-hydroxy-indoleacetic acid was also significantly increased in nucleus accumbens, indicating increased utilization of serotonin, along with norepinephrine levels which were also signficantly elevated in socially-isolated adolescent WKY. Differences in neurochemistry suggest that social or environmental stimuli during critical periods of brain and behavioural development can determine the developmental trajectories of implicated pathways.
Peter Mcguffin - One of the best experts on this subject based on the ideXlab platform.
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the Endogenous and reactive Depression subtypes revisited integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder
BMC Medicine, 2014Co-Authors: Karim Malki, Robert Keers, Maria G Tosto, Anbarasu Lourdusamy, Lucia Carboni, Enrico Domenici, Rudolf Uher, Peter McguffinAbstract:Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either ‘reactive’ or ‘Endogenous’ subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of ‘reactive’ or ‘Endogenous’ subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of ‘reactive’ and ‘Endogenous’ Depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic ‘stress’ protocols (maternal separation and Unpredictable Chronic Mild Stress) to model ‘reactive’ Depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of ‘Endogenous’ Depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse ‘reactive’ model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the ‘Endogenous’ rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that ‘Endogenous’ and ‘reactive’ subtypes of Depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of ‘reactive’ Depression caused by early stressors differs considerably from that of ‘reactive’ Depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar Depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD.
Reshma A Shetty - One of the best experts on this subject based on the ideXlab platform.
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immediate and delayed anxiety and Depression like profiles in the adolescent wistar kyoto rat model of Endogenous Depression following postweaning social isolation
Behavioural Brain Research, 2017Co-Authors: Reshma A Shetty, Monika SadanandaAbstract:In order to understand links that exist between inherited risk or predisposition, brain and behavioural development, endocrine regulation and social/environmental stimuli, animal models are crucial. The Wistar-Kyoto (WKY) rat has been shown to have validity as a model of adult and adolescent Depression. While sex- and age-specific differences in some of the face, predictive and construct validities of the model such as Depression-like behaviours have been established, anhedonia and anxiety using other induced anxiety paradigms such as elevated plus maze remain equivocal. First, post-weaning social isolation effects on inherent and induced anxiety behaviours were tested during two critical time periods, early- and mid-adolescence. Isolation induced immediate effects on novel environment-induced hyperactivity and anxiety-related behaviours. Adolescent WKYs demonstrated reduced 50-kHz ultrasonic vocalizations suggesting agoraphobia-like behaviours. Second, isolated rats, despite being subsequently social-/group-housed demonstrated longer lasting effects on social interaction measures and anhedonia. This establishes that the Depression-like profile observed during early- and mid-adolescence persists into late adolescence and early adulthood in WKY. Further, that interventions at a later stage during adolescence may not be able to reverse early adolescent effects in the context of pre-disposition, thus highlighting the irreversibility of being double-hit during critical time periods of brain and behavioural development and maturation.
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brief social isolation in the adolescent wistar kyoto rat model of Endogenous Depression alters corticosterone and regional monoamine concentrations
Neurochemical Research, 2017Co-Authors: Reshma A Shetty, Monika SadanandaAbstract:The Wistar-Kyoto rat (WKY) model has been suggested as a model of adult and adolescent Depression though face, predictive and construct validities of the model to Depression remain equivocal. The suitability of the WKY as a diathesis model that tests the double-hit hypothesis, particularly during critical periods of brain and behavioural development remains to be established. Here, effects of post-weaning social isolation were assessed during early adolescence (~30pnd) on behavioural despair and learned helplessness in the forced swim test (FST), plasma corticosterone levels and tissue monoamine concentrations in brain areas critically involved in Depression, such as prefrontal cortex, nucleus accumbens, striatum and hippocampus. Significantly increased immobility in the FST was observed in socially-isolated, adolescent WKY with a concomitant increase in corticosterone levels over and above the FST-induced stress. WKY also demonstrated a significantly increased release and utilization of dopamine, as manifested by levels of metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in nucleus accumbens, indicating that the large dopamine storage pool evident during adolescence induces greater dopamine release when stimulated. The serotonin metabolite 5-hydroxy-indoleacetic acid was also significantly increased in nucleus accumbens, indicating increased utilization of serotonin, along with norepinephrine levels which were also signficantly elevated in socially-isolated adolescent WKY. Differences in neurochemistry suggest that social or environmental stimuli during critical periods of brain and behavioural development can determine the developmental trajectories of implicated pathways.
Maria G Tosto - One of the best experts on this subject based on the ideXlab platform.
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the Endogenous and reactive Depression subtypes revisited integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder
BMC Medicine, 2014Co-Authors: Karim Malki, Robert Keers, Maria G Tosto, Anbarasu Lourdusamy, Lucia Carboni, Enrico Domenici, Rudolf Uher, Peter McguffinAbstract:Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either ‘reactive’ or ‘Endogenous’ subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of ‘reactive’ or ‘Endogenous’ subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of ‘reactive’ and ‘Endogenous’ Depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic ‘stress’ protocols (maternal separation and Unpredictable Chronic Mild Stress) to model ‘reactive’ Depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of ‘Endogenous’ Depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse ‘reactive’ model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the ‘Endogenous’ rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that ‘Endogenous’ and ‘reactive’ subtypes of Depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of ‘reactive’ Depression caused by early stressors differs considerably from that of ‘reactive’ Depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar Depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD.
Rudolf Uher - One of the best experts on this subject based on the ideXlab platform.
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the Endogenous and reactive Depression subtypes revisited integrative animal and human studies implicate multiple distinct molecular mechanisms underlying major depressive disorder
BMC Medicine, 2014Co-Authors: Karim Malki, Robert Keers, Maria G Tosto, Anbarasu Lourdusamy, Lucia Carboni, Enrico Domenici, Rudolf Uher, Peter McguffinAbstract:Traditional diagnoses of major depressive disorder (MDD) suggested that the presence or absence of stress prior to onset results in either ‘reactive’ or ‘Endogenous’ subtypes of the disorder, respectively. Several lines of research suggest that the biological underpinnings of ‘reactive’ or ‘Endogenous’ subtypes may also differ, resulting in differential response to treatment. We investigated this hypothesis by comparing the gene-expression profiles of three animal models of ‘reactive’ and ‘Endogenous’ Depression. We then translated these findings to clinical samples using a human post-mortem mRNA study. Affymetrix mouse whole-genome oligonucleotide arrays were used to measure gene expression from hippocampal tissues of 144 mice from the Genome-based Therapeutic Drugs for Depression (GENDEP) project. The study used four inbred mouse strains and two depressogenic ‘stress’ protocols (maternal separation and Unpredictable Chronic Mild Stress) to model ‘reactive’ Depression. Stress-related mRNA differences in mouse were compared with a parallel mRNA study using Flinders Sensitive and Resistant rat lines as a model of ‘Endogenous’ Depression. Convergent genes differentially expressed across the animal studies were used to inform candidate gene selection in a human mRNA post-mortem case control study from the Stanley Brain Consortium. In the mouse ‘reactive’ model, the expression of 350 genes changed in response to early stresses and 370 in response to late stresses. A minimal genetic overlap (less than 8.8%) was detected in response to both stress protocols, but 30% of these genes (21) were also differentially regulated in the ‘Endogenous’ rat study. This overlap is significantly greater than expected by chance. The VAMP-2 gene, differentially expressed across the rodent studies, was also significantly altered in the human study after correcting for multiple testing. Our results suggest that ‘Endogenous’ and ‘reactive’ subtypes of Depression are associated with largely distinct changes in gene-expression. However, they also suggest that the molecular signature of ‘reactive’ Depression caused by early stressors differs considerably from that of ‘reactive’ Depression caused by late stressors. A small set of genes was consistently dysregulated across each paradigm and in post-mortem brain tissue of depressed patients suggesting a final common pathway to the disorder. These genes included the VAMP-2 gene, which has previously been associated with Axis-I disorders including MDD, bipolar Depression, schizophrenia and with antidepressant treatment response. We also discuss the implications of our findings for disease classification, personalized medicine and case-control studies of MDD.