Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors

Bordt, Evan A.; Ceasrine, Alexis M; Bilbo, Staci D.

doi:10.1002/glia.23753

Cited by 80 publications

(64 citation statements)

References 128 publications

(227 reference statements)

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“…However, studies using different ELS procedures have yielded different outcomes. As previously described by Bordt, Caesrine, and Bilbo (2019), sex differences in microglial number and morphology exist during critical periods of development [167]. These developmental differences may mediate the diverse sex-specific reactivity to ELS [168].…”

Section: Perspectivesmentioning

confidence: 54%

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Catale

Gironda

Iacono

et al. 2020

JCM

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The putative effects of early-life stress (ELS) on later behavior and neurobiology have been widely investigated. Recently, microglia have been implicated in mediating some of the effects of ELS on behavior. In this review, findings from preclinical and clinical literature with a specific focus on microglial alterations induced by the exposure to ELS (i.e., exposure to behavioral stressors or environmental agents and infection) are summarized. These studies were utilized to interpret changes in developmental trajectories based on the time at which the stress occurred, as well as the paradigm used. ELS and microglial alterations were found to be associated with a wide array of deficits including cognitive performance, memory, reward processing, and processing of social stimuli. Four general conclusions emerged: (1) ELS interferes with microglial developmental programs, including their proliferation and death and their phagocytic activity; (2) this can affect neuronal and non-neuronal developmental processes, which are dynamic during development and for which microglial activity is instrumental; (3) the effects are extremely dependent on the time point at which the investigation is carried out; and (4) both pre- and postnatal ELS can prime microglial reactivity, indicating a long-lasting alteration, which has been implicated in behavioral abnormalities later in life.

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Section: Perspectivesmentioning

confidence: 54%

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Catale

Gironda

Iacono

et al. 2020

JCM

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“…However, four days later situation is reversed with males display more amoeboid microglia than females in the parietal cortex, hippocampus, and amygdala (Schwarz et al, 2012). However, a few studies to date reported that cerebellum microglia does not demonstrate any sex differences in shape and quantity (reviewed in (reviewed in Bordt, Ceasrine, & Bilbo, 2020; VanRyzin, Pickett, & McCarthy, 2018).…”

Section: Introductionmentioning

confidence: 99%

Postnatal alcohol exposure and adolescent exercise have opposite effects on cerebellar microglia in rat

Gursky

Johansson

Klintsova

2020

Intl J of Devlp Neuroscience

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Developmental alcohol exposure results in altered neuroimmune function in both humans and rodents. Given the critical role for the principle neuroimmune cell, microglia, in maintaining synaptic form and function, microglial dysfunction in the cerebellum may be an important mechanism underlying the aberrant cerebellar connectivity observed in rodent models of fetal alcohol spectrum disorders. Using an established rodent model of alcohol exposure during human third-trimester fetal development, we examine the cerebellum of male and female Long Evans rats to determine the impact of early postnatal alcohol exposure on cerebellar microglia, and the potential therapeutic effects of an adolescent intervention consisting of voluntary exercise (running). All cerebelli were examined at postnatal day 42 (i.e., late adolescence), and microglia were labeled with Iba1, a microglia-specific protein. Early postnatal alcohol exposure caused an increase in microglial density throughout cerebellum and a reduction in cerebellar volume, and a reduction in the proportion of fully ramified (often called "resting state") microglia selective to lobules 1-4. In contrast, adolescent exercise decreased microglial density throughout cerebellum and increased cerebellar volume, while activating microglia (as indicated by increases in amoeboid microglia, and reductions in fully and partially ramified microglia) selectively in lobules 1-4. These results suggest that adolescent exercise may be a suitable intervention to ameliorate alcohol-induced neuroimmune dysfunction as it alters microglia density and cerebellar volume in opposite to the effects of developmental alcohol exposure. Importantly, exercise intervention can be flexibly implemented well after the time window of vulnerability to alcohol.

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“…Microglia also interact with neurons through physical contact under homeostatic conditions [7,9,11,[33][34][35][36] . Microglia have recently been shown to contact dendrites and neuronal cell bodies in the normal adult brain [37,38] .…”

Section: Introductionmentioning

confidence: 99%

Microglial process convergence on axonal segments in health and disease

Benusa

Lafrenaye

2020

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Microglia dynamically interact with neurons influencing the development, structure, and function of neuronal networks. Recent studies suggest microglia may also influence neuronal activity by physically interacting with axonal domains responsible for action potential initiation and propagation. However, the nature of these microglial process interactions is not well understood. Microglial-axonal contacts are present early in development and persist through adulthood, implicating microglial interactions in the regulation of axonal integrity in both the developing and mature central nervous system. Moreover, changes in microglial-axonal contact have been described in disease states such as multiple sclerosis (MS) and traumatic brain injury (TBI). Depending on the disease state, there are increased associations with specific axonal segments. In MS, there is enhanced contact with the axon initial segment and node of Ranvier, while, in TBI, microglia alter interactions with axons at the site of injury, as well as at the axon initial segment. In this article, we review the interactions of microglial processes with axonal segments, analyzing their associations with various axonal domains and how these interactions may differ between MS and TBI. Furthermore, we discuss potential functional consequences and molecular mechanisms of these interactions and how these may differ among various types of microglial-axonal interactions.

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Microglia and sexual differentiation of the developing brain: A focus on ontogeny and intrinsic factors

Cited by 80 publications

References 128 publications

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Microglial Function in the Effects of Early-Life Stress on Brain and Behavioral Development

Postnatal alcohol exposure and adolescent exercise have opposite effects on cerebellar microglia in rat

Microglial process convergence on axonal segments in health and disease

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