Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

Bollinger, Justin L.; Collins, Kaitlyn; Patel, Rushi; Wellman, Cara L.

doi:10.1371/journal.pone.0187631

Cited by 85 publications

(67 citation statements)

References 75 publications

(107 reference statements)

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“…Consistent with previous studies in stress‐naïve rats (Baran, Armstrong, Niren, Hanna, & Conrad, ; Bollinger et al, ; Garrett & Wellman, ; Moench et al, ), chronic stress attenuated weight gain and increased adrenal‐to‐body weight ratios in male and female rats that were stressed in adolescence. However, unlike in our previous study (Moench & Wellman, ), in males the increased adrenal weight was maintained after 7 days of rest.…”

Section: Discussionsupporting

confidence: 89%

“…Stress in adulthood consisted of chronic restraint stress (3 hr/day for 10 days) in which rats were placed in a semi‐cylindrical Plexiglas tube (male: 16 cm × 6.5 cm × 5 cm; female: 15 cm × 6 cm × 4.5 cm, modified so the tail piece locks into place; Braintree Scientific, Braintree, MA). This procedure increases adrenal weights and attenuates weight gain in males and females (Bollinger, Collins, Patel, & Wellman, ; Moench et al, ).…”

Section: Methodsmentioning

confidence: 99%

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Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats

Breach

Moench

Wellman

2019

Developmental Neurobiology

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Adolescence is an important period for HPA axis development and synapse maturation and reorganization in the prefrontal cortex (PFC). Thus, stress during adolescence could alter stress-sensitive brain regions such as the PFC and may alter the impact of future stressors on these brain regions. Given that women are more susceptible to many stress-linked psychological disorders in which dysfunction of PFC is implicated, and that this increased vulnerability emerges in adolescence, stress during this time could have sex-dependent effects. Therefore, we investigated the effects of adolescent social instability stress (SIS) on dendritic morphology of Golgistained pyramidal cells in the medial PFC of adult male and female rats. We then examined dendritic reorganization following chronic restraint stress (CRS) with and without a rest period in adult rats that had been stressed in adolescence. Adolescent SIS conferred long-term alterations in prelimbic of males and females, whereby females show reduced apical length and basilar thin spine density and males show reduced basilar length. CRS in adulthood failed to produce immediate dendritic remodeling in SIS rats. However, CRS followed by a rest period reduced apical dendritic length and increases mushroom spine density in adolescently stressed adult males. Conversely, CRS followed by rest produced apical outgrowth and decreased mushroom spine density in adolescently stressed adult females. These results suggest that stress during adolescence alters development of the PFC and modulates stressinduced dendritic changes in adulthood. K E Y W O R D Sadolescent, chronic restraint stress, neuronal morphology, sex differences, social stress 840 | BREACH Et Al.How to cite this article: Breach MR, Moench KM, Wellman CL. Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats. Develop Neurobiol.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats

Breach

Moench

Wellman

2019

Developmental Neurobiology

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“…This is consistent with previous studies of sex differences in neuroimmune activity. Floor example, after chronic stress, males but not females showed ongoing microglial activation in basolateral amygdala (Bollinger, Collins, Patel, & Wellman, 2017). Alternatively, sex differences in strategy and mechanisms of fear memory formation may mediate differential susceptibility of males to disruption by prior Poly I:C (Keiser et al, 2017;Shansky, 2018).…”

Section: Discussionmentioning

confidence: 99%

Memory deficits in males and females long after subchronic immune challenge

Tchessalova

Tronson

2018

Preprint

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Memory impairments and cognitive decline persist long after recovery from major illness or injury, and correlate with increased risk of later dementia. Here we developed a subchronic peripheral immune challenge model to examine delayed and persistent memory impairments in females and in males. We show that intermittent injections of either lipopolysaccharide or Poly I:C cause memory decline in both sexes that are evident eight weeks after the immune challenge. Importantly, we observed sex-specific patterns of deficits.Females showed impairments in object recognition one week after challenge that persisted for at least eight weeks. In contrast, males had intact memory one week after the immune challenge but exhibited broad impairments in memory tasks including object recognition, and both context and tone fear conditioning several months later. The differential patterns of memory deficits in males and in females were observed without sustained microglial activation or changes in blood-brain barrier permeability. Together, these data suggest that transient neuroimmune activity results in differential vulnerabilities of females and males to memory decline after immune challenge. This model will be an important tool for determining the mechanisms in both sexes that contribute to memory impairments that develop over the weeks and months after recovery from illness. Future studies using this model will provide new insights into the role of chronic inflammation in the pathogenesis of long-lasting memory decline and dementias.

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“…As a result of the large number of correlations, only statistically significant associations ( P < 0.05) are reported. Outliers more than ±2 SD from the mean were removed from all analyses in accordance with standard laboratory procedures …”

Section: Methodsmentioning

confidence: 99%

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

Bollinger

Salinas

Fender

et al. 2019

J Neuroendocrinology

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Women are more susceptible to various stress‐linked psychopathologies, including depression. Dysfunction of the medial prefrontal cortex (mPFC) has been implicated in depression, and studies indicate sex differences in stress effects on mPFC structure and function. For example, chronic stress induces dendritic atrophy in the mPFC in male rats, yet dendritic growth in females. Recent findings suggest glial pathways toward depression. Glia are highly responsive to neuronal activity and function as critical regulators of synaptic plasticity. Preclinical models demonstrate stress‐induced microglial activation in mPFC in males, yet deactivation in females. By contrast, stress reduces astrocyte complexity in mPFC in male rats, whereas the effects in females are unknown. Glia possess receptors for most gonadal hormones and gonadal hormones are known to modulate neuronal activity. Thus, gonadal hormones represent a potential mechanism underlying sex differences in glia, as well as divergent stress effects. Therefore, we examined the role of gonadal hormones in sex‐specific stress effects on neuronal activity (ie FosB/ ΔFosB induction) and glia in the mPFC. The findings obtained indicate greater microglial activation in mPFC in females and a greater astrocyte area in males. Basal astrocyte morphology is modulated by androgens, whereas androgens or oestrogens dampen the microglial state in males. Astrocyte morphology is associated with neuronal activity in both sexes, regardless of hormonal condition. Chronic stress induced astrocytic atrophy in males, yet hypertrophy in females, with gonadal hormones partly regulating this difference. Stress effects on microglia are oestradiol‐dependent in females. Taken together, these data suggest sex‐specific, gonadal hormone‐dependent stress effects on astrocytes and microglia in the mPFC.

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Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner

Cited by 85 publications

References 75 publications

Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats

Social instability in adolescence differentially alters dendritic morphology in the medial prefrontal cortex and its response to stress in adult male and female rats

Memory deficits in males and females long after subchronic immune challenge

Gonadal hormones differentially regulate sex‐specific stress effects on glia in the medial prefrontal cortex

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