Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immune system components also regulate synapse formation and refinement in neurodevelopment. The complement pathway, associated with cell lysis and phagocytosis, is implicated in synaptic elimination. Aberrant adolescent synaptic pruning may underpin schizophrenia onset; thus, changes in cortical complement activity during human development is of major interest. Complement is genetically linked to schizophrenia via increased C4 copy number variants, but developmental trajectory of complement expression in the human brain is undetermined. As complement increases during periods of active synaptic engulfment in rodents, we hypothesized that complement expression would increase during postnatal development in humans, particularly during adolescence. Using human postmortem prefrontal cortex, we observe that complement activator (C1QB and C3) transcripts peak in early neurodevelopment, and are highest in toddlers, declining in teenagers (all ANCOVAs between F=2.41 -3.325, p=0.01-0.05) We found that C4 protein was higher at 1-5yrs (H=16.378, p=0.012) whereas C3 protein levels are unchanged with age. The microglial complement receptor subunit CD11b increased in mRNA early in life and peaked in toddler brain (ANCOVA: pH, F=4.186, p=0.003). Complement inhibitors (CD46 and CD55) increased early in life, but failed to decrease like complement activators (both ANCOVAs, F>4.4, p<0.01), These data suggest activation of complement in the human prefrontal cortex occurs between 1-5 years. We do not find evidence of induction of complement factors during adolescence and instead find increased or sustained levels of complement inhibitor mRNA at maturation. Dysregulation of these typical patterns of complement may predispose the brain to neurodevelopmental disorders such as autism or schizophrenia.
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PMID:Trajectory of Change in Brain Complement Factors from Neonatal to Young Adult Humans. 3319 Feb 36