title: Cytokine effects on cortical neuron MAP-2 immunoreactivity: implications for schizophrenia.
abstract: BACKGROUND
  Cytokines demonstrate diverse actions in the brain and modulate systemic and central nervous system (CNS) responses to injury, infection, and inflammation. Cytokines in the CNS are elevated during infection and ischemia, two neurodevelopmental insults associated with increased schizophrenia risk. We hypothesize that cytokine-mediated neuronal injury during development may contribute to schizophrenia pathophysiology, causing subtle alterations in neuronal number and density.
  
  
  METHODS
  We examined cytokine regulation of neuronal number in embryonic day 18 rat cortical cultures using MAP-2 immunohistochemistry. Mixed cultures derived from frontal cortex were fixed and stained after 48-hour exposure to the proinflammatory interleukin-1beta (IL-1beta), interleukin-6 (IL-6), or tumor necrosis factor-alpha (TNF-alpha; 0, 10, 100, or 1000 units/mL).
  
  
  RESULTS
  IL-1beta (maximum effect 35%) and IL-6 (maximum effect 29%) produced dose-dependent decreases in the number of cells (neurons) immunoreactive for MAP-2 antibody, suggesting decreased neuronal survival. TNF-alpha also tended to decrease MAP-2 immunostaining at the highest dose tested.
  
  
  CONCLUSIONS
  Our data suggest a role for cytokines in the modulation of neuronal survival during neurodevelopment, a finding potentially relevant to schizophrenia pathophysiology. If cytokine-mediated neuronal injury proves to be a common response to gestational insults associated with increased schizophrenia risk, the pharmacologic modulation of these molecules may have clinical utility.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Marx
authors.forename: L F
authors.initials: LF
authors.lastname: Jarskog
authors.forename: J M
authors.initials: JM
authors.lastname: Lauder
authors.forename: J A
authors.initials: JA
authors.lastname: Lieberman
authors.forename: J H
authors.initials: JH
authors.lastname: Gilmore
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D016207:Cytokines / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005865:Gestational Age; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; C489788:MAP2 protein, human; C489787:MAP2 protein, rat; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins