scholarly journals Repeated exposure with short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eun-Hwa Lee ◽  
Jin-Young Park ◽  
Hye-Jin Kwon ◽  
Pyung-Lim Han

AbstractChronic stress induces adaptive changes in the brain via the cumulative action of glucocorticoids, which is associated with mood disorders. Here we show that repeated daily five-minute restraint resolves pre-existing stress-induced depressive-like behavior in mice. Repeated injection of glucocorticoids in low doses mimics the anti-depressive effects of short-term stress. Repeated exposure to short-term stress and injection of glucocorticoids activate neurons in largely overlapping regions of the brain, as shown by c-Fos staining, and reverse distinct stress-induced gene expression profiles. Chemogenetic inhibition of neurons in the prelimbic cortex projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis results in anti-depressive effects similarly to short-term stress exposure, while only inhibition of neurons in the prelimbic cortex projecting to the bed nucleus of the stria terminalis rescues defective glucocorticoid release. In summary, we show that short-term stress can reverse adaptively altered stress gains and resolve stress-induced depressive-like behavior.

2008 ◽  
Vol 100 (6) ◽  
pp. 3429-3436 ◽  
Author(s):  
Frank Z. Nagy ◽  
Denis Paré

The amygdala and bed nucleus of the stria terminalis (BNST) are thought to subserve distinct functions, with the former mediating rapid fear responses to discrete sensory cues and the latter longer “anxiety-like” states in response to diffuse environmental contingencies. However, these structures are reciprocally connected and their projection sites overlap extensively. To shed light on the significance of BNST–amygdala connections, we compared the antidromic response latencies of BNST and central amygdala (CE) neurons to brain stem stimulation. Whereas the frequency distribution of latencies was unimodal in BNST neurons (∼10-ms mode), that of CE neurons was bimodal (∼10- and ∼30-ms modes). However, after stria terminalis (ST) lesions, only short-latency antidromic responses were observed, suggesting that CE axons with long conduction times course through the ST. Compared with the direct route, the ST greatly lengthens the path of CE axons to the brain stem, an apparently disadvantageous arrangement. Because BNST and CE share major excitatory basolateral amygdala (BL) inputs, lengthening the path of CE axons might allow synchronization of BNST and CE impulses to brain stem when activated by BL. To test this, we applied electrical BL stimuli and compared orthodromic response latencies in CE and BNST neurons. The latency difference between CE and BNST neurons to BL stimuli approximated that seen between the antidromic responses of BNST cells and CE neurons with long conduction times. These results point to a hitherto unsuspected level of temporal coordination between the inputs and outputs of CE and BNST neurons, supporting the idea of shared functions.


2020 ◽  
Author(s):  
Eun-Hwa Lee ◽  
Jin-Young Park ◽  
Hye-jin Kwon ◽  
Pyung-Lim Han

Abstract Chronic stress produces adaptive changes in the brain via the cumulative action of glucocorticoids, which causes psychiatric illnesses such as depression. Here we show that a behavioral method implementing weak stress does not strengthen but resolves existing stress gains. Chronic stress produces persistent depressive behaviors in mice, and repeated daily treatment with 5-min restraint produces antidepressive effects. Repeated treatment with low-dose glucocorticoids mimics the anti-depressive effects of weak stress. Repeated weak stress or low-dose glucocorticoid treatment distinctively activates the prelimbic cortex (PL), and reverses the stress-induced altered gene expression profiles. Chemogenetic inhibition of PL outputs projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis (BNST) dissipates antidepressive effects of weak stress, but only the PL-to-BNST circuit produces changes in dysregulated glucocorticoid release. Our results suggest that behavioral appraisal by implementing weak stress can resolve adaptively altered stress gains and rectify stress-induced depressive behaviors.


2009 ◽  
Vol 84 (4) ◽  
pp. 271-286 ◽  
Author(s):  
Miyuki Shimada ◽  
Satomi Kameo ◽  
Norio Sugawara ◽  
Kozue Yaginuma-Sakurai ◽  
Naoyuki Kurokawa ◽  
...  

Author(s):  
Louis J. G. Gooren

Transsexualism is the condition in which a person with apparently normal somatic sexual differentiation is convinced that he/she is actually a member of the opposite sex. It is associated with an irresistible urge to be hormonally and surgically adapted to that sex. Traditionally transsexualism has been conceptualized as a purely psychological phenomenon, but research on the brains of male-to-female transsexuals has found that the sexual differentiation of the brain—the bed nucleus of the stria terminalis (BSTC) and the hypothalamic uncinate nucleus—had followed a female pattern (1). This finding may lead to a concept of transsexualism as a form of intersex, where the sexual differentiation of the brain (which in mammals also undergoes sexual differentiation) is not consistent with the other variables of sex, such as chromosomal pattern, nature of the gonad and nature of internal/external genitalia. Thus it can be argued that transsexualism is a sexual differentiation disorder.


2004 ◽  
Vol 97 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Lichao Chen ◽  
Deborah Duricka ◽  
Scott Nelson ◽  
Sanjib Mukherjee ◽  
Stewart G. Bohnet ◽  
...  

Influenza viral infection induces increases in non-rapid eye movement sleep and decreases in rapid eye movement sleep in normal mice. An array of cytokines is produced during the infection, and some of them, such as IL-1β and TNF-α, are well-defined somnogenic substances. It is suggested that nitric oxide (NO) may mediate the sleep-promoting effects of these cytokines. In this study, we use mice with targeted disruptions of either the neuronal NO synthase (nNOS) or the inducible NO synthase (iNOS) gene, commonly referred to as nNOS or iNOS knockouts (KOs), to investigate sleep changes after influenza viral challenge. We report that the magnitude of viral-induced non-rapid eye movement sleep responses in both nNOS KOs and iNOS KOs was less than that of their respective controls. In addition, the duration of rapid eye movement sleep in nNOS KO mice did not decrease compared with baseline values. All strains of mice had similar viral titers and cytokine gene expression profiles in the lungs. Virus was not isolated from the brains of any strain. However, gene expression in the brain stem differed between nNOS KOs and their controls: mRNA for the interferon-induced gene 2′,5′-oligoadenylate synthase 1a was elevated in nNOS KOs relative to their controls at 15 h, and IL-1β mRNA was elevated in nNOS KOs relative to their controls at 48 h. Our results suggest that NO synthesized by both nNOS and iNOS plays a role in virus-induced sleep changes and that nNOS may modulate cytokine expression in the brain.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-42-SCI-42
Author(s):  
Norman N. Iscove

Abstract Abstract SCI-42 For many years a distinction was drawn between prospectively separable murine HSC populations with long-term, essentially permanent reconstituting potential (LT-HSC), versus HSC populations yielding short-term engraftment lasting only 4 – 6 weeks after transplantation (ST-HSC). Recent work based on transplantation of single cells shows that highly purified populations of LT-HSC prepared by standard sorting parameters consist in fact predominantly of a distinct, newly recognized class of intermediate- term reconstituting cells (IT-HSC) whose grafts endure longer than short-term HSC but also eventually fail (1). IT-HSC are separable from long-term reconstituting cells on the basis of expression of more alpha2 integrin and less SLAM150. Crucial to recognition of the distinction between LT- and IT-HSC are the endpoints used to evaluate reconstitution. If blood erythroid or myeloid reconstitution is measured, IT reconstitution is readily distinguished by the disappearance of these elements by 16 wk post-transplant. If instead reconstitution is measured simply by presence of blood leukocytes of donor origin, which in the mouse are almost entirely lymphocytes, the distinction is not made because lymphoid elements persist even in fading IT clones to 24 wk or beyond. The observations imply a need for reinterpretation of most of the published descriptions of the biology and gene expression profiles previously attributed to LT-HSC but in fact derived from analysis of populations that consisted mainly of IT-HSC. The capacity now to separate LT- from IT-HSC creates new opportunities for probing the mechanisms that specify and sustain long term function in the former but not the latter. 1. Benveniste P, Frelin C, Janmohamed S, Barbara M, Herrington R, Hyam D, Iscove NN. Intermediate-term hematopoietic stem cells with extended but time-limited reconstitution potential. Cell Stem Cell. 2010;6:48–58 Disclosures: No relevant conflicts of interest to declare.


PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65732 ◽  
Author(s):  
Asuka Kamei ◽  
Yuki Watanabe ◽  
Kaori Kondo ◽  
Shinji Okada ◽  
Fumika Shinozaki ◽  
...  

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