D-Serine Ameliorates Neonatal PolyI:C Treatment^|^ndash;Induced Emotional and Cognitive Impairments in Adult Mice

Abstract

Abstract. Polyriboinosinic-polyribocytidilic acid (polyI:C) is a synthetic analog that elicits virallike immune responses in mammals. We have recently found that polyI:C treatment in neonatal mice induced abnormalities of emotional, cognitive, and sensorimotor gating and dysfunction of glutamatergic neurotransmission in adulthood. In this study, we investigated the effect of the NMDA-receptor co-agonist D-serine on polyI:C-induced behavioral abnormalities in mice. Neonatal ICR mice were repeatedly injected with polyI:C for 5 days from postnatal day 2 to 6. At 10 weeks, sensorimotor gating function was analyzed in the prepulse inhibition (PPI) test. Emotional function was analyzed in open field and social interaction tests. Cognitive function was analyzed by novel object recognition tests. D-Serine dose-dependently improved polyI:C-induced impairment of emotional and cognitive behaviors whereas it had no effect on PPI deficit in adults. The ameliorating effects of D-serine were antagonized by pretreatment with an NMDA-receptor antagonist, MK-801. Although the mRNA level of D-amino acid oxidase (DAAO) was increased in the prefrontal cortex and hippocampus of neonatal polyI:C-treated mice in adulthood, no changes were observed in D-serine content and DAAO enzymatic activity. These results suggest that Dserine ameliorates emotional and cognitive impairments of the polyI:C-treated mice through potentiating NMDA receptor activity.

Aging with Traumatic Brain Injury: Effects of Age at Injury on Behavioral Outcome following Diffuse Brain Injury in Rats

“…The open field task was used to assess locomotor activity and anxiety-like behavior, as previously described [29]. At 8 months after injury, the rats were placed in an empty arena (70 × 70 × 46 cm, W × L × H) and allowed to explore freely for 5 min.…”

Acute Post-Traumatic Sleep May Define Vulnerability to a Second Traumatic Brain Injury in Mice

“…The open field task was used to assess locomotor activity and anxiety-like behavior as previously described. 40 At 7, 14, and 28 DPI, mice were placed in an empty arena (45 ×45 ×30 cm, W ×L ×H) and allowed to explore freely for five minutes. Mouse movement was tracked by an overhead camera and the distance traveled, time spent in the center of the arena (29.5 ×29.5 cm), and number of entries into the center were calculated using EthoVision XT 10 software (Noldus Information Technology, Leesburg, VA).…”

The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents

“…Interestingly, long-term increases in D-serine through a genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO) was shown to reverse the social interaction deficits of Grin1 D481N mice, without altering social investigation in wild-type mice [90], suggesting that overstimulation of the glycine-binding site of the NMDA receptors does not negatively affect social interaction. Furthermore, Nagai et al [91] have shown that D-serine ameliorates social interaction deficits by potentiating the NMDA receptor activity. As such, mice treated with polyriboinosinic-polyribocytidilic acid (polyI:C; a synthetic analog that elicits viral-like immune responses) during early postnatal development show social interaction deficits which could be improved by D-serine treatment in adulthood, an effect which was antagonized by pretreatment with the un-competitive NMDA-receptor antagonist MK-801 [91].…”

“…Furthermore, Nagai et al [91] have shown that D-serine ameliorates social interaction deficits by potentiating the NMDA receptor activity. As such, mice treated with polyriboinosinic-polyribocytidilic acid (polyI:C; a synthetic analog that elicits viral-like immune responses) during early postnatal development show social interaction deficits which could be improved by D-serine treatment in adulthood, an effect which was antagonized by pretreatment with the un-competitive NMDA-receptor antagonist MK-801 [91].…”