ABSTRACT
OBJECTIVES: There is a growing evidence to suggest that the antecedents of some adult diseases can be traced back to their fetal origins. Despite extensive research on such diseases, to our knowledge, there has been no research investigating the relationship between the origins of multiple sclerosis (MS) disease and maternal infections. The aim of this study was to examine the role of prenatal exposure to endotoxin in fetal programming with respect to induction of susceptibility/vulnerability to MS. METHODS: The pregnant dams were administered a single intraperitoneal injection of lipopolysaccharide in gestational day 10. The male offspring were weighed and examined for clinical signs of experimental autoimmune encephalomyelitis in a blinded fashion within 36 days after immunization (postnatal day 63-98). RESULTS: Our data provide the evidence showing prenatal exposures to higher doses of Lipopolysaccharide resulted in an earlier onset of the disease, an augmentation of its clinical signs, and lower body weight in the prenatally Lipopolysaccharide -treated C57BL/6 mice after the immunization. DISCUSSION: Therefore, the present research can provide evidence that prenatal stress may play a role in enhancing the clinical symptoms of experimental autoimmune encephalomyelitis/MS.
Subject(s)
Encephalomyelitis, Autoimmune, Experimental/physiopathology , Fetal Development/physiology , Prenatal Exposure Delayed Effects/physiopathology , Animals , Body Weight/drug effects , Body Weight/physiology , Disease Models, Animal , Dose-Response Relationship, Drug , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Female , Fetal Development/drug effects , Male , Mice , Mice, Inbred C57BL , Myelin-Oligodendrocyte Glycoprotein/toxicity , Peptide Fragments/toxicity , Polysaccharides/toxicity , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Severity of Illness Index , Time FactorsABSTRACT
Growing evidence suggests that early life events are critical determinants for disorders later in life. According to a comprehensive number of epidemiological/animal studies, exposure to lipopolysaccharide, causes alteration in pro-inflammatory cytokine levels, hypothalamic-pituitary-adrenal functioning and the hormonal system which may contribute to behavioral and neurological injuries. In this study we investigated the effects of lipopolysaccharide administration on physiological parameters in pregnant dams and their male offspring aged 9 weeks. In gestational Day 10, pregnant mice were injected intrapritoneally with Salmonella enterica lipopolysaccharide to model prenatal exposure to infection. The following results were obtained for offspring from dams stressed during pregnancy: (a) reduced anxiety-related behavior in the elevated plus maze; (b) reduced food and water intake; (c) reduced body weight from birth up to postnatal Day 40. The observed data provide experimental evidence showing that prenatal stress can have complex and long-lasting physiological/behavioral consequences in offspring.
