Sex differences in depressive-like behaviour may relate to imbalance of microglia activation in the hippocampus

Liu, Linlin; Li, Jiamei; Su, Wen‐Jun; Wang, Bo; Jiang, Chun‐Lei

doi:10.1016/j.bbi.2019.06.012

Cited by 96 publications

(77 citation statements)

References 46 publications

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“…Anxiety might play a role in the establishment of CMS-induced depression, but some stressors are known to be aversive without being anxiety-focused, e.g. tilted cages, changes in circadian rhythms by continuous illumination or heat stress 43 , while tail handling is known to induce anxiety 10 . Perhaps the permanent exposition to the anxiogenic handling is one explanation for the specific effect on males-as some studies showed how female rodents typically display less anxiety-like behaviour 44,45 .…”

Section: Discussionmentioning

confidence: 99%

The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific

Sensini

Inta

Palme

et al. 2020

Sci Rep

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Handling is a well-known source of stress to laboratory animals and can affect variability of results and even compromise animal welfare. The conventional tail handling in mice has been shown to induce aversion and anxiety-like behaviour. Recent findings demonstrate that the use of alternative handling techniques, e.g. tunnel handling, can mitigate negative handling-induced effects. Here, we show that technique and frequency of handling influence affective behaviour and stress hormone release of subjects in a sex-dependent manner. While frequent tail handling led to a reduction of wellbeing-associated burrowing and increased despair-like behaviour in male mice, females seemed unaffected. Instead, they displayed a stress response to a low handling frequency, which was not detectable in males. This could suggest that in terms of refinement, the impact in handling could differ between the sexes. Independently from this observation, both sexes preferred to interact with the tunnel. Mice generally explored the tunnel more often than the tail-handling hands of the experimenter and showed more positively rated approaches, e.g. touching or climbing, and at the same time, less defensive burrowing, indicating a strong preference for the tunnel.

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Section: Discussionmentioning

confidence: 99%

The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific

Sensini

Inta

Palme

et al. 2020

Sci Rep

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“…Previous preclinical and clinical research has supported the finding that females with abnormal phenotypes and BDNF levels in specific brain areas are more vulnerable to stress than males. For instance, female mice with BDNF deletions in the forebrain or hippocampus are more sensitive to chronic unpredictable stress and exhibit depression-like behaviors; on the contrary, loss of BDNF in the same brain regions does not increase stress susceptibility in male mice [158,159]. MS stress can increase sensitivity to neuropathic pain on inducing depression-like behaviors only in female mice, but not in males, which is associated with differential BDNF expression in the hippocampus and striatum between the two sexes [160].…”

Section: Sex Differences In Stress-associated Bdnf Alterationsmentioning

confidence: 99%

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

Zhang

Wang

Sun

2020

IJMS

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Brain-derived neurotrophic factor (BDNF), a critical member of the neurotrophic family, plays an important role in multiple stress-related mental disorders. Although alterations in BDNF in multiple brain regions of individuals experiencing stress have been demonstrated in previous studies, it appears that a set of elements are involved in the complex regulation. In this review, we summarize the specific brain regions with altered BDNF expression during stress exposure. How various environmental factors, including both physical and psychological stress, affect the expression of BDNF in specific brain regions are further summarized. Moreover, epigenetic regulation of BDNF, including DNA methylation, histone modification, and noncoding RNA, in response to diverse types of stress, as well as sex differences in the sensitivity of BDNF to the stress response, is also summarized. Clarification of the underlying role of BDNF in the stress process will promote our understanding of the pathology of stress-linked mental disorders and provide a potent target for the future treatment of stress-related illness.

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“…Chronic mild stress (CMS) or chronic variable stress (CVS), an experimental stressor whereby the subject is placed under mild and ever-changing stress-provoking conditions (Hodes et al, 2015;Wang et al, 2018;Johnson et al, 2020), has been shown to cause an increase in gene expression for inflammatory factors such as IL-6, IL-1ß and TNF-α in the hippocampus (Wang et al, 2018;Liu et al, 2019). In studies directly identifying sex-specific effects of CMS on hippocampal inflammation, both males and females demonstrated increased proinflammatory cytokines, but males exhibited increases in mRNA iNOS and IL-1b while females demonstrated increases in TNF-a and reductions in antiinflammatory cytokines IL-10 and IL1ra (Liu et al, 2019). Moreover, ratios of pro-to antiinflammatory cytokines indicated that females were more prone to a pro-inflammatory environment.…”

Section: Inflammatory Response To Preclinical Models Of Stress In Malmentioning

confidence: 99%

Sex Differences in the Inflammatory Consequences of Stress: Implications for Pharmacotherapy

Martinez-Muniz

Wood

2020

J Pharmacol Exp Ther

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Sex differences in depressive-like behaviour may relate to imbalance of microglia activation in the hippocampus

Cited by 96 publications

References 46 publications

The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific

The impact of handling technique and handling frequency on laboratory mouse welfare is sex-specific

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

Sex Differences in the Inflammatory Consequences of Stress: Implications for Pharmacotherapy

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