主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
BACKGROUND:
Maternal immune activation (MIA) during pregnancy negatively transforms offspring brain development, resulting in neurochemical abnormalities and neuropsychiatric disorder behaviors. Since hypofunction of N-methyl-D-aspartate receptors (NMDARs) in offspring after MIA may be a convergence point for psychiatric symptoms, particularly cognitive deficits. This study was undertaken to evaluate whether NMDAR modulator could reduce MIA-induced behavioral impairments in the adult offspring.
METHODS:
Using a prenatal infection model, the pregnant ICR mice were administrated with double-stranded RNA polyinosinic:polycytidylic acid [poly (I:C)] or saline on embryonic days 12-17 (E12 to E17) for six days. The offspring (P70-84) were given (i.p.) daily with NMDAR modulator (100 mg/kg) or vehicle for two weeks. Adult offspring were tested for spontaneous locomotion, social interaction, stereotyped behavior, and restraint stress induced behavioral responses. The expressing levels of cell surface markers from adult offspring peripheral blood were also determined by flow cytometry.
RESULTS:
In spontaneous locomotion test (LMT), MIA offspring traveled a greater total distance and center area distance in open field compared with their control groups. MIA offspring at adult stage exhibited a less social interaction and a higher level of stereotypic digging and marble burying compared to control offspring. Moreover, peripheral blood CD11b+ cells from MIA adult offspring expressed a higher levels of activation markers, CD86 and major histocompatibility complex class II (MHC class II, I-A/I-E). Subchronic administration of NMDAR modulator for two weeks attenuated the hyperlocomotion activity and social interaction deficits, but not stereotypic digging, induced by MIA. Moreover, NMDAR modulator alleviated the social interaction deficits and reduction of locomotion, but not alter stereotypic digging in MIA offspring after acute restraint stress.
CONCLUSIONS:
This work raises the possibility that dietary supplementation with NMDAR modulator may open new avenues for a successful attenuation of behavioral alterations relevant to psychiatric disorder in the adult MIA offspring.
