Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice

Hellwig, Sabine; Brioschi, Simone; Dieni, Sandra; Frings, Lars; Masuch, Annette; Blank, Thomas; Biber, Knut

doi:10.1016/j.bbi.2015.11.008

Cited by 202 publications

(172 citation statements)

References 55 publications

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“…While process shortening and increased soma size has traditionally been associated with microglial activation, increasing evidence points to the fact that there are many types of microglial “activation”. In fact, hyper-ramification of microglia in the PFC and hippocampus has been observed in other models of stress, such as repeated swimming in a chronic behavioral despair model (Hellwig et al, 2016) and chronic restraint stress (Hinwood et al, 2013). In contrast to the traditional pro-inflammatory form of microglial activation, little is known about hyper-ramification of microglia or about the function of hyper-ramified microglia (Hinwood et al, 2013).…”

Section: Discussionmentioning

confidence: 92%

Adolescent food restriction in rats alters prefrontal cortex microglia in an experience-dependent manner

Ganguly

Thompson

Gildawie

et al. 2018

Stress

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Microglia are resident immune cells of the brain that can regulate neural communication and excitability. Any environmental influence on microglial activity has the potential to alter subsequent neural physiology and behavior. Within the prefrontal cortex, several types of stressors have been shown to increase microglial expression of activation markers such as ionized calcium-binding adapter molecule-1 (Iba-1), which suggests altered microglial activity. Recent reports in rodents suggest that exposure to forms of early-life stress such as maternal separation can alter microglial responsivity to subsequent challenges. Several learning paradigms used in rodents require food restriction to provoke motivational states that facilitate approach behaviors. Here, we tested whether food restriction (increasing from 13 g/day-23 g/day in males and 10 g/day-20 g/day in females, which reduced body weight to 72-84% free-fed weight) in adolescent rats is a sufficient challenge to affect microglial Iba-1 expression, and whether previous exposure to postnatal maternal separation influenced microglial outcomes. We measured prefrontal cortex Iba-1 expression and microglial morphology after 20 days of ad libitum or restricted food availability in males and females with or without exposure to maternal separation. Food-restricted animals displayed higher levels of Iba-1 in the prefrontal cortex, with hyper-ramified microglial morphology in maternally separated males and control females, compared to those that were free-fed. Together, our data provide evidence that food restriction paradigms may have unintended effects in some behavioral protocols.

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Section: Discussionmentioning

confidence: 92%

Adolescent food restriction in rats alters prefrontal cortex microglia in an experience-dependent manner

Ganguly

Thompson

Gildawie

et al. 2018

Stress

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“…Prenatal and early-life stress also increase anxiety, increase despair-like behavior, increase stress reactivity, and decrease social interactions later in life (Holland et al, 2014; Rayen et al, 2011; Vallée et al, 1997; Wei et al, 2010). Lastly, fractalkine knockout mice, a model with disrupted microglial physiology and lower microglial density during the early postnatal period, showed decreased reactivity to stress and social behavior deficits in adulthood (Hellwig et al, 2016; Zhan et al, 2014). However, the knockout effects are lifelong thus making it hard to determine what effects are developmental in origin.…”

Section: Discussionmentioning

confidence: 99%

“…In development, models that are thought to activate microglia or alter their function, such as perinatal stress or inflammatory challenge, show changes in social, anxiety and despair-like behavior, as well as stress reactivity (Choi et al, 2016; Hellwig et al, 2016; Lin et al, 2012; Majidi-Zolbanin et al, 2013; Meyer, 2006; Vallée et al, 1997; Wei et al, 2010; Zhan et al, 2014). These results suggest that microglia may be more important for developmental programming of behavior than the maintenance of behavior in adulthood.…”

Section: Introductionmentioning

confidence: 99%

Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats

Nelson

Lenz

2017

Behavioural Brain Research

102

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Microglia, the innate immune cells of the central nervous system, regulate brain development by promoting cell genesis, pruning synapses, and removing dying, newly-born or progenitor cells. However, the role of microglia in the early life programming of behavior under normal conditions is not well characterized. We used central infusion of liposomal clodronate to selectively deplete microglia from the neonatal rat brain and subsequently assessed the impact of microglial depletion on programming of juvenile and adult motivated behaviors. Liposomal clodronate treatment on postnatal days one and four led to greater than 70% loss of forebrain microglia by postnatal day 6 that lasted for approximately ten days. Neonatal microglia depletion led to reduced juvenile and adult anxiety behavior on the elevated plus maze and open field test, and increased locomotor activity. On a test of juvenile social play, microglial depletion led to decreased chase behaviors relative to control animals. There was no change in active social behavior in adults on a reciprocal social interaction test, but there was decreased passive interaction time and an increased number of social avoidance behaviors in clodronate treated rats relative to controls. There was an overall decrease in behavioral despair on the forced swim test in adult rats treated neonatally with clodronate. Females, but not males, treated neonatally with clodronate showed a blunted corticosterone response after acute stress in adulthood. These results show that microglia are important for the early life programming of juvenile and adult motivated behavior.

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“…Furthermore, studies using animal models have described the effects of fractalkine on brain physiology, which are associated with depression and anxiety (6). Mice deficient in CX3CR1 cells have been shown to exhibit resistance to stress-induced depression-like behavior and to not respond to antidepressant treatment (19). Therefore, high levels of systemic fractalkine seems to be linked to the incidence of depression and anxiety.…”

Section: Discussionmentioning

confidence: 99%

Fractalkine (C‑X3‑C motif chemokine ligand 1) as a potential biomarker for depression and anxiety in colorectal cancer patients

et al. 2017

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Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice

Cited by 202 publications

References 55 publications

Adolescent food restriction in rats alters prefrontal cortex microglia in an experience-dependent manner

Adolescent food restriction in rats alters prefrontal cortex microglia in an experience-dependent manner

Microglia depletion in early life programs persistent changes in social, mood-related, and locomotor behavior in male and female rats

Fractalkine (C‑X3‑C motif chemokine ligand 1) as a potential biomarker for depression and anxiety in colorectal cancer patients

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