P.1.d.010 Effects of maternal separation and antidepressant treatment on adult brain and behavior in a rat model of depression

AbstractThe efforts of many neuroscientists are directed toward understanding the appreciable plasticity of the brain and behavior. In recent years, epigenetics has become a core of this focus as a prime mechanistic candidate for behavioral modifications. Animal models have been instrumental in advancing our understanding of environmentally driven changes to the epigenome in the developing and adult brain. This review focuses mainly on such discoveries driven by adverse environments along with their associated behavioral outcomes. While much of the evidence discussed focuses on epigenetics within the central nervous system, several peripheral studies in humans who have experienced significant adversity are also highlighted. As we continue to unravel the link between epigenetics and phenotype, discerning the complexity and specificity of epigenetic changes induced by environments is an important step toward understanding optimal development and how to prevent or ameliorate behavioral deficits bred by disruptive environments.

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Dehydroepiandrosterone Metabolism by 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase in Adult Zebra Finch Brain: Sex Difference and Rapid Effect of Stress

Endocrinology ◽

10.1210/en.2003-0883 ◽

2004 ◽

Vol 145 (4) ◽

pp. 1668-1677 ◽

Cited By ~ 106

Author(s):

Kiran K. Soma ◽

Noel A. Alday ◽

Michaela Hau ◽

Barney A. Schlinger

Keyword(s):

Sex Differences ◽

Sex Difference ◽

Zebra Finch ◽

Sex Steroids ◽

Hydroxysteroid Dehydrogenase ◽

Adult Brain ◽

Brain And Behavior ◽

Rapid Modulation ◽

And Behavior ◽

The Brain

Abstract Dehydroepiandrosterone (DHEA) is a precursor to sex steroids such as androstenedione (AE), testosterone (T), and estrogens. DHEA has potent effects on brain and behavior, although the mechanisms remain unclear. One possible mechanism of action is that DHEA is converted within the brain to sex steroids. 3β-Hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (3β-HSD) catalyzes the conversion of DHEA to AE. AE can then be converted to T and estrogen within the brain. We test the hypothesis that 3β-HSD is expressed in the adult brain in a region- and sex-specific manner using the zebra finch (Taeniopygia guttata), a songbird with robust sex differences in song behavior and telencephalic song nuclei. In zebra finch brain, DHEA is converted by 3β-HSD to AE and subsequently to estrogens and 5α- and 5β-reduced androgens. 3β-HSD activity is highest in the diencephalon and telencephalon. In animals killed within 2–3 min of disturbance, baseline 3β-HSD activity in portions of the telencephalon is higher in females than males. Acute restraint stress (10 min) decreases 3β-HSD activity in females but not in males, and in stressed animals, telencephalic 3β-HSD activity is greater in males than in females. Thus, the baseline sex difference is rapidly reversed by stress. To our knowledge, this is the first demonstration of 1) brain region differences in DHEA metabolism by 3β-HSD, 2) rapid modulation of 3β-HSD activity, and 3) sex differences in brain 3β-HSD and regulation by stress. Songbirds are good animal models for studying the regulation and functions of DHEA and neurosteroids in the nervous system.

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Effects of experimental suppression of active (REM) sleep during early development upon adult brain and behavior in the rat

Developmental Brain Research ◽

10.1016/0165-3806(83)90184-0 ◽

1983 ◽

Vol 7 (2-3) ◽

pp. 277-286 ◽

Cited By ~ 152

Author(s):

M. Mirmiran ◽

J. Scholtens ◽

N.E. Van de Poll ◽

H.B.M. Uylings ◽

J. Van der Gugten ◽

...

Keyword(s):

Early Development ◽

Rem Sleep ◽

Adult Brain ◽

Brain And Behavior ◽

And Behavior

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Fluoxetine effects on behavior and adult hippocampal neurogenesis in female C57BL/6J mice across the estrous cycle

10.1101/368449 ◽

2018 ◽

Cited By ~ 2

Author(s):

Christine N. Yohn ◽

Sophie Shifman ◽

Alexander Garino ◽

Emma Diethorn ◽

Leshya Bokka ◽

...

Keyword(s):

Estrous Cycle ◽

Antidepressant Treatment ◽

Hippocampal Neurogenesis ◽

Adult Hippocampal Neurogenesis ◽

List Type ◽

Female Mice ◽

Chronic Fluoxetine ◽

Brain And Behavior ◽

And Behavior ◽

The Impact

AbstractSome mood disorders, such as major depressive disorder, are more prevalent in women than in men. However, historically preclinical studies in rodents have a lower inclusion rate of females than males, possibly due to the fact that behavior can be affected by the estrous cycle. Several studies have demonstrated that chronic antidepressant treatment can decrease anxiety-like behaviors and increase adult hippocampal neurogenesis in male rodents. However, very few studies have conclusively looked at the effects of antidepressants on behavior and neurogenesis across the estrous cycle in naturally cycling female rodents. Here we analyze the effects of chronic treatment with the selective serotonin reuptake inhibitor (SSRI) fluoxetine (Prozac) on behavior and adult hippocampal neurogenesis in naturally cycling C57BL/6J females across all four phases of the estrous cycle. Interestingly, we find that the effects of fluoxetine on both behavior and adult hippocampal neurogenesis are driven by mice specifically in the estrus or diestrus phases of the estrous cycle. Taken together our data is the first to illustrate the impact of fluoxetine on brain and behavior across all four stages of the murine estrous cycle.HighlightsChronic fluoxetine reduces anxiety-like behaviors in naturally cycling female miceChronic fluoxetine increases adult hippocampal neurogenesis in naturally cycling female miceThe effects of chronic fluoxetine on behavior and adult hippocampal neurogenesis are driven by the estrus and diestrus phases of the estrous cycle

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CGRP in a gene–environment interaction model for depression: effects of antidepressant treatment

Acta Neuropsychiatrica ◽

10.1017/neu.2018.31 ◽

2018 ◽

Vol 31 (2) ◽

pp. 93-99 ◽

Cited By ~ 2

Author(s):

Francesco Angelucci ◽

Bart A Ellenbroek ◽

Aram El Khoury ◽

Aleksander A. Mathé

Keyword(s):

Environmental Factors ◽

Rat Model ◽

Maternal Separation ◽

Antidepressant Treatment ◽

Interaction Model ◽

Brain Regions ◽

Environment Interaction ◽

Brain Levels ◽

Gene Environment ◽

Genetic And Environmental Factors

AbstractObjectiveGenetic and environmental factors interact in the development of major depressive disorder (MDD). While neurobiological correlates have only partially been elucidated, altered levels of calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) in animal models and in the cerebrospinal fluid of depressed patients were reported, suggesting that CGRP may be involved in the pathophysiology and/or be a trait marker of MDD. However, changes in CGRP brain levels resulting from interactions between genetic and environmental risk factors and the response to antidepressant treatment have not been explored.MethodsWe therefore superimposed maternal separation (MS) onto a genetic rat model (Flinders-sensitive and -resistant lines, FSL/FRL) of depression, treated these rats with antidepressants (escitalopram and nortriptyline) and measured CGRP-LI in selected brain regions.ResultsCGRP was elevated in the frontal cortex, hippocampus and amygdala (but not in the hypothalamus) of FSL rats. However, MS did not significantly alter levels of this peptide. Likewise, there were no significant interactions between the genetic and environmental factors. Most importantly, neither escitalopram nor nortriptyline significantly altered brain CGRP levels.ConclusionOur data demonstrate that increased brain levels of CGRP are present in a well-established rat model of depression. Given that antidepressants have virtually no effect on the brain level of this peptide, our study indicates that further research is needed to evaluate the functional role of CGRP in the FSL model for depression.

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