Chronic social stress blunts core body temperature and molecular rhythms of Rbm3 and Cirbp in mouse lateral habenula

Abstract

Chronic social stress in mice causes behavioural and physiological changes that result in perturbed rhythms of body temperature, activity and sleep-wake cycle. To further understand the link between mood disorders and temperature rhythmicity in mice that are resilient or susceptible to stress, we measured core body temperature (Tcore) before and after exposure to chronic social defeat stress (CSDS). We found that Tcore amplitudes of stress-resilient and susceptible mice are dampened during exposure to CSDS. However, following CSDS, resilient mice recovered temperature amplitude faster than susceptible mice. Furthermore, the interdaily stability (IS) of temperature rhythms was fragmented in stress-exposed mice during CSDS, which recovered to control levels following stress. There were minimal changes in locomotor activity after stress exposure which correlates with regular rhythmic expression of Prok2 - an output signal of the suprachiasmatic nucleus. We also determined that expression of thermosensitive genes Rbm3 and Cirbp in the lateral habenula (LHb) were blunted 1 day after CSDS. Rhythmic expression of these genes recovered 10 days later. Overall, we show that CSDS blunts Tcore and thermosensitive gene rhythms. Tcore rhythm recovery is faster in stress-resilient mice, but Rbm3 and Cirbp recovery is uniform across the phenotypes.

CIRBP Stabilizes Slc7a11 mRNA to Sustain the SLC7A11/GPX4 Antioxidant Axis and Limit Ferroptosis in Doxorubicin-Induced Cardiotoxicity

“…Our study further links CIRBP specifically to ferroptosis, a regulated form of cell death driven by lipid peroxidation and compromised antioxidant defenses [ 14 , 15 ], offering novel theoretical insights into RNA-protein interactions under chemotherapeutic stress [ 28 , 29 ]. Detailed analyses demonstrated that CIRBP deficiency exacerbates DOX-induced cardiac injury, oxidative stress, and cardiac remodeling, reaffirming its critical protective role in maintaining cardiac structure and function, consistent with previous findings regarding RNA-binding proteins’ roles in stress resilience [ 17 , 30 ].…”

CIRBP Stabilizes Slc7a11 mRNA to Sustain the SLC7A11/GPX4 Antioxidant Axis and Limit Ferroptosis in Doxorubicin-Induced Cardiotoxicity

“…Our study further links CIRBP specifically to ferroptosis, a regulated form of cell death driven by lipid peroxidation and compromised antioxidant defenses [ 14 , 15 ], offering novel theoretical insights into RNA-protein interactions under chemotherapeutic stress [ 28 , 29 ]. Detailed analyses demonstrated that CIRBP deficiency exacerbates DOX-induced cardiac injury, oxidative stress, and cardiac remodeling, reaffirming its critical protective role in maintaining cardiac structure and function, consistent with previous findings regarding RNA-binding proteins’ roles in stress resilience [ 17 , 30 ].…”

Aging reprograms the response to chronic stress

“…Physiological readouts similarly identified an age-dependent divergence of stress responses. In young mice, CVS induced circadian changes in body temperature as previously described 19,20 . These included reduced head and back temperature, and increased tail temperature, suggesting a possible change in peripheral vascular tone.…”

Nighttime-specific gene expression changes in suprachiasmatic nucleus and habenula are associated with resiliency to chronic social stress

“…Such segregation allows investigations into underlying mechanisms that promote resilience to stress (Anacker et al, 2018;Cathomas et al, 2019). Chronic social stress in rodents disrupts body temperature, heart rate, locomotor activity rhythms and sleep patterns (Haniffa et al, 2023;Meerlo et al, 2002;Radwan et al, 2021aRadwan et al, , 2021b. We have shown that LHb cells projecting to the DRN of stress-susceptible mice exhibit blunted diurnal activity while stress-resilient and stress-naïve mice exhibit robust daily rhythm in activity (H. Liu et al, 2021).…”

CIRBP Stabilizes Slc7a11 mRNA to Sustain the SLC7A11/GPX4 Antioxidant Axis and Limit Ferroptosis in Doxorubicin-Induced Cardiotoxicity

“…Our study further links CIRBP specifically to ferroptosis, a regulated form of cell death driven by lipid peroxidation and compromised antioxidant defenses [ 14 , 15 ], offering novel theoretical insights into RNA-protein interactions under chemotherapeutic stress [ 28 , 29 ]. Detailed analyses demonstrated that CIRBP deficiency exacerbates DOX-induced cardiac injury, oxidative stress, and cardiac remodeling, reaffirming its critical protective role in maintaining cardiac structure and function, consistent with previous findings regarding RNA-binding proteins’ roles in stress resilience [ 17 , 30 ].…”

Aging reprograms the response to chronic stress

“…Physiological readouts similarly identified an age-dependent divergence of stress responses. In young mice, CVS induced circadian changes in body temperature as previously described 19,20 . These included reduced head and back temperature, and increased tail temperature, suggesting a possible change in peripheral vascular tone.…”

Nighttime-specific gene expression changes in suprachiasmatic nucleus and habenula are associated with resiliency to chronic social stress

“…Such segregation allows investigations into underlying mechanisms that promote resilience to stress (Anacker et al, 2018;Cathomas et al, 2019). Chronic social stress in rodents disrupts body temperature, heart rate, locomotor activity rhythms and sleep patterns (Haniffa et al, 2023;Meerlo et al, 2002;Radwan et al, 2021aRadwan et al, , 2021b. We have shown that LHb cells projecting to the DRN of stress-susceptible mice exhibit blunted diurnal activity while stress-resilient and stress-naïve mice exhibit robust daily rhythm in activity (H. Liu et al, 2021).…”

CIRBP Stabilizes Slc7a11 mRNA to Sustain the SLC7A11/GPX4 Antioxidant Axis and Limit Ferroptosis in Doxorubicin-Induced Cardiotoxicity

“…Our study further links CIRBP specifically to ferroptosis, a regulated form of cell death driven by lipid peroxidation and compromised antioxidant defenses [ 14 , 15 ], offering novel theoretical insights into RNA-protein interactions under chemotherapeutic stress [ 28 , 29 ]. Detailed analyses demonstrated that CIRBP deficiency exacerbates DOX-induced cardiac injury, oxidative stress, and cardiac remodeling, reaffirming its critical protective role in maintaining cardiac structure and function, consistent with previous findings regarding RNA-binding proteins’ roles in stress resilience [ 17 , 30 ].…”

Aging reprograms the response to chronic stress

“…Physiological readouts similarly identified an age-dependent divergence of stress responses. In young mice, CVS induced circadian changes in body temperature as previously described 19,20 . These included reduced head and back temperature, and increased tail temperature, suggesting a possible change in peripheral vascular tone.…”

Nighttime-specific gene expression changes in suprachiasmatic nucleus and habenula are associated with resiliency to chronic social stress

“…Such segregation allows investigations into underlying mechanisms that promote resilience to stress (Anacker et al, 2018;Cathomas et al, 2019). Chronic social stress in rodents disrupts body temperature, heart rate, locomotor activity rhythms and sleep patterns (Haniffa et al, 2023;Meerlo et al, 2002;Radwan et al, 2021aRadwan et al, , 2021b. We have shown that LHb cells projecting to the DRN of stress-susceptible mice exhibit blunted diurnal activity while stress-resilient and stress-naïve mice exhibit robust daily rhythm in activity (H. Liu et al, 2021).…”