The nuclear factor-κB inhibitor pyrrolidine dithiocarbamate reduces polyinosinic-polycytidilic acid-induced immune response in pregnant rats and the behavioral defects of their adult offspring.
BACKGROUND
Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. It is assumed that the maternal infection increases the immune response, leading to neurodevelopmental disorders in the offspring. Maternal polyinosinic-polycytidilic acid (PolyI:C) treatment induces a wide range of characteristics in the offspring mimicking some schizophrenia symptoms in humans. These observations are consistent with the neurodevelopmental hypothesis of schizophrenia.


METHODS
We examined whether suppression of the maternal immune response could prevent neurodevelopmental disorders in adult offspring. PolyI:C or saline was administered to early pregnant rats to mimic maternal infection, and the maternal immune response represented by tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) levels was determined by enzyme-linked immunosorbent assays (ELISA). The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) was used to suppress the maternal immune response. Neurodevelopmental disorders in adult offspring were examined by prepulse inhibition (PPI), passive avoidance, and active avoidance tests.


RESULTS
PolyI:C administration to early pregnant rats led to elevated serum cytokine levels as shown by massive increases in serum TNF-α and IL-10 levels. The adult offspring showed defects in prepulse inhibition, and passive avoidance and active avoidance tests. PDTC intervention in early pregnant rats suppressed cytokine increases and reduced the severity of neurodevelopmental defects in adult offspring.


CONCLUSIONS
Our findings suggest that PDTC can suppress the maternal immune response induced by PolyI:C and partially prevent neurodevelopmental disorders of adult offspring.
Department of Psychiatry, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Xueqin
X
Song
Wenqiang
W
Li
Yongfeng
Y
Yang
Jingping
J
Zhao
Chengdi
C
Jiang
Wei
W
Li
Luxian
L
Lv
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D005260:Female; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000276:immunology; D009422:Nervous System Diseases / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D011070:Poly I-C / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000975:Antioxidants; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C020972:pyrrolidine dithiocarbamic acid; D011070:Poly I-C