Neonatal immune challenge poses a sex-specific risk for epigenetic microglial reprogramming and behavioral impairment.
Marius SchwabenlandOmar MossadAnnika SievertAdam G PeresElena RingelSebastian BaaschJulia KolterGiulia CasconeNikolaos DokalisAndreas VlachosZsolt RuzsicsPhilipp HennekeMarco PrinzThomas BlankPublished in: Nature communications (2023)
While the precise processes underlying a sex bias in the development of central nervous system (CNS) disorders are unknown, there is growing evidence that an early life immune activation can contribute to the disease pathogenesis. When we mimicked an early systemic viral infection or applied murine cytomegalovirus (MCMV) systemically in neonatal female and male mice, only male adolescent mice presented behavioral deficits, including reduced social behavior and cognition. This was paralleled by an increased amount of infiltrating T cells in the brain parenchyma, enhanced interferon-γ (IFNγ) signaling, and epigenetic reprogramming of microglial cells. These microglial cells showed increased phagocytic activity, which resulted in abnormal loss of excitatory synapses within the hippocampal brain region. None of these alterations were seen in female adolescent mice. Our findings underscore the early postnatal period's susceptibility to cause sex-dependent long-term CNS deficiencies following infections.
Keyphrases
- induced apoptosis
- early life
- mental health
- cell cycle arrest
- young adults
- inflammatory response
- white matter
- gene expression
- lps induced
- lipopolysaccharide induced
- resting state
- dna methylation
- neuropathic pain
- blood brain barrier
- healthcare
- functional connectivity
- dendritic cells
- traumatic brain injury
- signaling pathway
- endoplasmic reticulum stress
- high fat diet induced
- cell death
- spinal cord injury
- preterm infants
- oxidative stress
- epstein barr virus
- mild cognitive impairment
- cerebrospinal fluid
- skeletal muscle
- multiple sclerosis
- cell proliferation
- childhood cancer