Long-term maternal separation potentiates depressive-like behaviours and neuroinflammation in adult male C57/BL6J mice

Zhou, Lin; Wu, Zuotian; Wang, Gaohua; Xiao, Ling; Wang, Huiling; Sun, Lihua; Xie, Yumeng

doi:10.1016/j.pbb.2020.172953

Cited by 30 publications

(22 citation statements)

References 59 publications

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“…It indicated that the changes in adult depression-like behaviors were induced by the prolonged MS experience. The results were consistent with the previous studies [ 31 , 34 , 35 ]. About OFT, it is applied to measure spontaneous activity.…”

Section: Discussionsupporting

confidence: 94%

“…And the underlying effect was associated with epigenetic changes of H3K4me3 in the murine prefrontal cortex [ 30 ]. However, another study reported that MS increased neuroinflammatory activation and inhibited CRMP2-induced neuroprotection, thereby leading to the impairment of neuroplasticity after subsequent exposure to CUMS [ 31 ]. To better model depression in humans and detect biochemical changes caused by depression, we used the CUMS model in this study.…”

Section: Discussionmentioning

confidence: 99%

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Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice

Bian

et al. 2021

BioMed Research International

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Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice

Bian

et al. 2021

BioMed Research International

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“…However, it remains difficult to study this model to mice because MS led to only mild behavioral anomalies in adult mice (Millstein and Holmes, 2007). Moloney et al (2012) developed a mouse model of MS stress-induced visceral hyperalgesia as measured by CRD (Moloney et al, 2012); from then on, MS of mice model were extensively conducted to study the mechanism underlying the pathogenesis of IBS, such as intestinal dysbiosis, intestinal dysfunction, intestinal permeability alteration, and IBS-like anxiety and depression behaviors (De Palma et al, 2015;Li et al, 2017;Riba et al, 2017;Rincel et al, 2019;Zhou et al, 2020). Indeed, compared with the rat model, the mouse model of MS had the advantages of its small size, relatively high reproductivity, inexpensive, and can be genetically manipulated (Kong et al, 2013;Shaqour et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

et al. 2022

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Early life stress (ELS) disposes to functional gastrointestinal diseases in adult, such as irritable bowel syndrome (IBS). Maternal separation (MS) is a well-known animal model of IBS and has been shown to induce visceral hypersensitivity in adult rats and mice. However, to the best of our knowledge, it has not been reported whether MS induces visceral hypersensitivity in young mice, such as the post-weaning mice. Moreover, the method for evaluation of visceral sensitivity also has not been described. Accordingly, the present study aims to evaluate the visceral sensitivity caused by MS in post-weaning mice and develop a novel and small size distention balloon for assessment of visceral sensitivity of such mice. Male pups of C57BL/6 mice were randomly divided into two groups, MS (n = 12) and non-separation (NS) (n = 10). MS pups were separated from the dams through postnatal days (PND) 2 to 14, while NS pups were undisturbed. After, all pups stayed with respective dams and were weaned at PND 22. Visceral sensitivity was evaluated by colorectal distention (CRD) with a novel and small size distention balloon at PND 25. The threshold of abdominal withdrawal reflex (AWR) scores were significantly lower in MS than NS. In addition, AWR scores at different pressures of CRD were significantly higher in MS than NS. The results demonstrate that MS induced visceral hypersensitivity in post-weaning mice. The designed small size distention balloon for evaluation of visceral sensitivity is of significance to further study the pathophysiology of IBS from early life to adulthood.

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“…However, the effects of ELS on microglia function and neuroinflammation are long-term effects. Several rodent models have demonstrated that ELS could impact the development of microglia and dysregulate microglia functional and increase neuroinflammation levels when the rodents reach adolescence and adulthood [ 55 , 59 , 60 , 61 ]. Another limitation is that we focused on microglial NLRP3 only.…”

Section: Discussionmentioning

confidence: 99%

NLRP3 Inflammasome Is Involved in Cocaine-Mediated Potentiation on Behavioral Changes in CX3CR1-Deficient Mice

Guo

Chivero

Callen

et al. 2021

JPM

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Microglia, the primary immunocompetent cells of the brain, are suggested to play a role in the development of drug addiction. Previous studies have identified the microglia-derived pro-inflammatory factor IL1β can promote the progression of cocaine addiction. Additionally, the activation status of microglia and “two-hit hypothesis” have been proposed in the field of drug addiction to explain how early life stress (ELS) could significantly increase the incidence of drug addiction in later life. However, the mechanisms underlying microglia prime and full activation and their roles in drug addiction remain greatly unexplored. Here, we employed CX3CR1-GFP mice (CX3CR1 functional deficiency, CX3CR1−/−) to explore whether primed microglia could potentiate cocaine-mediated behavioral changes and the possible underlying mechanisms. CX3CR1−/− mice revealed higher hyperlocomotion activity and conditional place preference than wild-type (WT) mice did under cocaine administration. In parallel, CX3CR1−/− mice showed higher activity of NLR family pyrin domain-containing 3 (NLRP3) inflammasome than WT mice. Interestingly, CX3CR1 deficiency itself could prime NLRP3 signaling by increasing the expression of NLPR3 and affect lysosome biogenesis under basal conditions. Taken together, our findings demonstrated that the functional status of microglia could have an impact on cocaine-mediated reward effects, and NLRP3 inflammasome activity was associated with this phenomenon. This study was consistent with the two-hit hypothesis and provided solid evidence to support the involvement of microglia in drug addiction. Targeting the NLRP3 inflammasome may represent a novel therapeutic approach for ameliorating or blocking the development of drug addiction.

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Long-term maternal separation potentiates depressive-like behaviours and neuroinflammation in adult male C57/BL6J mice

Cited by 30 publications

References 59 publications

Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice

Prolonged Maternal Separation Induces the Depression-Like Behavior Susceptibility to Chronic Unpredictable Mild Stress Exposure in Mice

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

NLRP3 Inflammasome Is Involved in Cocaine-Mediated Potentiation on Behavioral Changes in CX3CR1-Deficient Mice

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