Abstract
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.
Highlights
Exposure to childhood adversities is a risk factor for developing psychopathologies later in life
This study employed the positron emission tomography (PET) radioligand [11C]PBR28, which binds to the 18 kDa mitochondrial translocator protein (TSPO), which is thought to be expressed in active microglia during brain injury and neurodegeneration and is considered a marker of neuroinflammation [26,27]
The literature collected and described in this review shows that early-life stress (ELS) has robust effects on microglial functionality and morphology, and that ELS-induced microglial activation mediates the emergence of brain and behavioral alterations
Summary
Exposure to childhood adversities (i.e., abuse, neglect, physical illness, economic difficulty) is a risk factor for developing psychopathologies later in life. A history of early-life stress (ELS) is strongly associated with almost all classes of mental disorders, including mood disorders, anxiety disorders, and substance use disorders [1]. Biological embedding such as alterations in brain structure, function, connectivity, and epigenetic programming has been consistently reported in individuals exposed to adversities in childhood [2,3]. It has been suggested that exposure to ELS could modify the trajectories of brain maturation [4,5,6], increasing vulnerability to psychopathologies later in life.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have