Early life adversity, microglial dysfunction linked to abnormal adult stress responses, psychiatric disorders

     Poorly functioning microglia, the brain's immune cells, promote abnormal responses to stress in adulthood in individuals with early life adversity (ELA), according to a new study led by UC Irvine researchers.

May be related to mental illness

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During brain development, microglia prune unnecessary synapses to form delicate functional circuits

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Disruption of this process leaves too many synapses, altering behavior and hormonal responses in response to further stress in future life

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The study, titled "Early-stress induced impairment of microglial pruning of excitatory synapses on? immature CRH-expressing neurons provokes aberrant adult stress responses," was published today in Cell Reports

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Much neuroscience and brain disease research has focused on neurons in the brain

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This study highlights that, in addition to neurons, other brain cells, especially immune cells, play critical roles in brain health and disease," said UC Irvine School of Medicine Anatomy and Neurobiology, Pediatrics, Neurology, Physiology and Physiology.

Tallie Z.

Baram, Distinguished Professor in the Department of Biophysics, said

: "Neuroimmune interactions represent a new and important avenue for understanding and treating several brain and psychiatric disorders that other UCI researchers have linked with Alzheimer's mutism link

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Brain development is influenced by both genes and early life experiences

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Several psychiatric disorders characterized by abnormal stress responses frequently arise after ELA, but their impact on the maturation of stress-related brain circuits is unclear
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In this study, transgenic mice of both sexes were placed in a temperature-controlled, quiet, uncrowded environment with 12 hours of light and 12 hours of darkness, with free access to food and water
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Control dams were housed in cages with a standard amount of corn husk bedding and nesting material
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The ELA group had only half the litter and nesting material
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Real-time interactions of microglia (green) and stress-sensitive neurons (red) in the brains of transgenic mice
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The researchers found that ELA increased functional excitatory synapses in stress-sensitive hypothalamic corticotropin-releasing hormone (CRH)-expressing neurons as neighboring microglia disrupted developing synapses in young mice due to pruning
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These neuroimmune interactions during development make CRH cells and their mice more susceptible to stress
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"Our findings show that ELA causes a reduction in the dynamics of microglia processes during sensitive periods
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We know this is a direct effect of ELA because we artificially activate microglia in stressed neonatal mice , thereby preventing synaptic excess and abnormal stress responses in adulthood," Baram said
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"The next step is to determine whether the molecules that cause microglial dysfunction can be used to prevent their dysfunction and resulting vulnerability to stress. This is transformative for people."