Sphingosine-1-phosphate receptor 3 in the medial prefrontal cortex promotes stress resilience by reducing inflammatory processes

Corbett, Brian; Luz, Sandra; Arner, Jay; Pearson-Leary, Jiah; Sengupta, Abhishek; Taylor, Deanne; Gehrman, Philip; Ross, Richard; Bhatnagar, Seema

doi:10.1038/s41467-019-10904-8

Cited by 47 publications

(78 citation statements)

References 65 publications

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“…The coping response of experimental animals exposed to stress has been used in other studies to distinguish between resilient and vulnerable individuals. For example, male rats were classified as having an active or passive coping strategy according to their latency of submission (Wood et al, 2010(Wood et al, , 2013Pearson-Leary et al, 2017;Grafe et al, 2018;Corbett et al, 2019) and the index of flee behavior in a social interaction test performed after RSD has also been applied to mice (Henriques-Alves and Queiroz, 2016).…”

Section: Resilience To the Long-term Effects Of Rsd On Cocaine Cpp Ismentioning

confidence: 99%

Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice

Calpe-López

García-Pardo

Martínez-Caballero

et al. 2020

Front. Behav. Neurosci.

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The relationship between stress and drug use is well demonstrated. Stress-induced by repeated social defeat (RSD) enhances the conditioned place preference (CPP) induced by cocaine in mice. The phenomenon of resilience understood as the ability of subjects to overcome the negative effects of stress is the focus of increasing interest. Our aim is to characterize the behavior of resilient animals with respect to the effects of RSD on the CPP induced by cocaine. To this end, 25 male C57BL/6 mice were exposed to stress by RSD during late adolescence, while other 15 male mice did not undergo stress (controls). On the 2 days following the last defeat, all the animals carried out the elevated plus maze (EPM) and Hole Board, Social Interaction, Tail Suspension and Splash tests. Three weeks later, all the animals performed the CPP paradigm with a low dose of cocaine (1 mg/kg). Exposure to RSD decreased all measurements related to the open arms of the EPM. It also reduced social interaction, immobility in the tail suspension test (TST) and grooming in the splash test. RSD exposure also increased the sensitivity of the mice to the rewarding effects of cocaine, since only defeated animals acquired CPP. Several behavioral traits were related to resilience to the potentiating effect of RSD on cocaine CPP. Mice that showed less submission during defeat episodes, a lower percentage of time in the open arms of the EPM, low novelty-seeking, high social interaction, greater immobility in the TST and a higher frequency of grooming were those that were resilient to the long-term effects of social defeat on cocaine reward since they behaved like controls and did not develop CPP. These results suggest that the behavioral profile of resilient defeated mice is characterized by an active coping response during episodes of defeat, a greater concern for potential dangers, less reactivity in a situation of inevitable moderate stress and fewer depressive-like symptoms after stress. Determining the neurobehavioral substrates of resilience is the first step towards developing behavioral or pharmacological interventions that increase resilience in individuals at a high risk of suffering from stress.

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Section: Resilience To the Long-term Effects Of Rsd On Cocaine Cpp Ismentioning

confidence: 99%

Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice

Calpe-López

García-Pardo

Martínez-Caballero

et al. 2020

Front. Behav. Neurosci.

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“…On hippocampal slices, it has been shown that S1PR1 signaling influences NMDAR properties [101]. Similarly, ablation of S1PR3 impairs neuronal hippocampal excitability in vitro [102] and reduces inflammatory processes in medial prefrontal cortex in mice [103], both areas involved in pain processing [104]. However, more in-depth studies on S1P signaling also need to be addressed towards other brain structures responsible for pain modulation, such as cingulate cortex, thalamus, periaqueductal grey, and rostroventral medulla.…”

Section: S1p Axis In Central Sensitizationmentioning

confidence: 99%

Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics

Squillace

Spiegel

Salvemini

2020

Trends in Pharmacological Sciences

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“…Research reports show the impact of chronic unpredictable stress on cellular integration and active involvement of certain brain regions such as DG, prefrontal cortex, and hippocampus [ 4 , 5 ]. The medial prefrontal cortex is an essential neural substrate helping in modulating the hypothalamic-pituitary-adrenal axis during the exposure to stressful situations [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic unpredictable stress-induced inflammation and quantitative analysis of neurons of distinct brain regions in Wistar rat model of comorbid depression

et al. 2020

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Background and Aim: Depression and anxiety are the most prominent neuropsychiatric disease and have been considered as the most burdensome diseases of society. The hippocampus and prefrontal cortex have a prominent role in stress-induced neurological disorders. Chronic unpredictable stress exposed rats are a perfect model in understanding comorbid depression and anxiety disorders. The inflammatory response occurring in the body has been linked to C-reactive protein (CRP) in many diseased conditions. The present research primarily focus on the possible correlation of Cortisol, CRP level and neuronal assay in different regions of hippocampus, dentate gyrus (DG), and prefrontal cortex. Materials and Methods: The control group of rats (n=6) was not exposed to any stress. Whereas, the experimental stress group (n=6) of rats was exposed to various stressors for 15 days. After the experimentation procedures, the blood samples were collected and brain dissection was done. The neurons in the prefrontal cortex, the DG along with various hippocampal regions was counted. Statistical analysis was performed using student's t-test and p<0.05 was expressed as statistically significant. Results: Animals exposed to chronic unpredictable stressors showed a significant (p<0.0001) decrease in the neuronal count in prefrontal cortex and hippocampus. A significant rise in the serum cortisol (p<0.0001) and CRP (p<0.001) was witnessed in the stressed group. Conclusion: Our results demonstrate that chronic unpredictable stress exposure has affected neurogenesis in prefrontal cortex and hippocampal regions. Decreased neurogenesis was well in coordinance with the increase in cortisol and CRP. The chronic unpredictable stress-induced inflammatory response correlated to various brain regions might provoke insights into a variety of new drugs targeting neurogenesis.

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Sphingosine-1-phosphate receptor 3 in the medial prefrontal cortex promotes stress resilience by reducing inflammatory processes

Cited by 47 publications

References 65 publications

Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice

Behavioral Traits Associated With Resilience to the Effects of Repeated Social Defeat on Cocaine-Induced Conditioned Place Preference in Mice

Targeting the Sphingosine-1-Phosphate Axis for Developing Non-narcotic Pain Therapeutics

Chronic unpredictable stress-induced inflammation and quantitative analysis of neurons of distinct brain regions in Wistar rat model of comorbid depression

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