Neonatal Behavioral Changes in Rats With Gestational Exposure to Lipopolysaccharide: A Prenatal Infection Model for Developmental Neuropsychiatric Disorders

Abstract

Exposure to prenatal infections has been widely associated with the increased risk for neuropsychiatric disorders of developmental origin such as schizophrenia and autism. Although several behavioral and cognitive deficits have been detected during adulthood in rodent models of prenatal infections, early behavioral changes have not been well characterized. In a prenatal lipopolysaccharide (LPS) model, we have previously observed significant alterations in the neuronal cytoarchitecture during early postnatal life. In the present study, we aimed to investigate the potential effects of prenatal immune activation on early neurophenotypic presentations using a set of behavioral test battery. Female Sprague-Dawley rats were administered with 100 μg/kg LPS (intraperitoneally) at gestational days 15 and 16. During the first postnatal week, we found no significant effect on maternal behavior or mother-pup interaction by this treatment. Also, no major changes in physical developmental milestones of pups were noted from postnatal (P) days P6 to P16. Importantly, prenatal LPS-exposed pups had a significant decrease in the number and duration of ultrasonic vocalization calls at P3 and P5. Prenatal LPS treatment also led to impairments in nest-seeking behavior and odor-stroke associative learning in neonatal rats at P8 and P9. At the molecular level, we detected significant decrease in the expression of cortical 5HT1A and 5HT1B messenger RNA at P3. These data suggest that prenatal exposure to an immune activator can significantly impair the social/communicative behavior in the neonate offspring, which may be relevant to childhood and premorbid abnormalities reported in autism and schizophrenia subjects.

Malaria in Pregnancy: An Unrecognized Risk Factor for Neuropsychiatric Disease in Offspring?

“…The neurochemical changes in malaria-exposed offspring are consistent with reports of altered brain chemistry in neuropsychiatric disorders [62,70,71]. In further support of this hypothesis, several inflammatory factors including IL-6, TNF and CRP that are implicated as mediators of maternal immune activation-related neuropsychiatric disorders [51,53,54,72] are increased in MIP [9,15,73,74].…”

Deep brain stimulation improves behavior and modulates neural circuits in a rodent model of schizophrenia

“…The well-documented association between intrauterine inflammatory/immunologic responses (e.g. to infectious agents) and the susceptibility for the development of schizophrenia promoted the establishment of the so-called "maternal immune activation" (MIA) models (Baharnoori et al, 2012;Piontkewitz et al, 2012a). These involve administering pregnant dams with viruses, bacterial products (i.e.…”

Prenatal zinc supplementation to lipopolysaccharide infected female rats prevents neurochemical, behavioral and biochemical deficits produced in infants

“…on prenatally LPS treated pups and pups showed impairment in behavior. [51,52] Maternal zinc supplementation prevents aberrant behavior in object recognition task in mice off spring following early gestational exposure of LPS. [53] In accordance with the previous reports in case of present study also an improvement in memory following maternal zinc supplementation was observed.…”