Maternal Stress Combined with @entity4183 Leads to Comorbid Autistic-Like Behavior and XXXX in a @entity35 Model.

@entity1 @entity410 @entity131 @entity3152 @entity146 @entity16 @entity2438 @entity302 @entity35 @entity4183
@entity1 @entity2438 is comorbid with @entity302 , yet, little is known about the causes or risk factors leading to this combined @entity16 . Although genetic predisposition can play a substantial role, our objective was to investigate whether maternal environmental factors alone could be sufficient.We examined the independent and combined effects of maternal stress and @entity4183 (used to arrest @entity3152 ), @entity2438 risk factors in @entity1 , on measures of both @entity2438 -like behavior and @entity302 in @entity35 . Pregnant dams were exposed to mild stress (foot shocks at 1 week intervals) throughout pregnancy. Pups were injected with @entity4183 on postnatal days 2-5.Either maternal stress or @entity4183 resulted in @entity2438 -like behaviors in offspring (stereotyped/repetitive behaviors and deficits in social interaction or communication), but neither resulted in @entity302 . However, their combination resulted in severe behavioral symptoms, as well as spontaneous recurrent @entity410 in 45% and @entity302 in 100%, of the @entity35 . @entity131 (GFAP reactivity) was correlated with both @entity146 and spontaneous @entity410 .We conclude that prenatal insults alone can cause comorbid @entity2438 and @entity302 but it requires a combination of teratogens to achieve this; testing single teratogens independently and not examining combinatorial effects may fail to reveal key risk factors in @entity1 . Moreover, astrogliosis may be common to both teratogens. This new animal model of combined @entity2438 and @entity302 permits the experimental investigation of both the cellular mechanisms and potential intervention strategies for this debilitating comorbid syndrome. SIGNIFICANCE STATEMENT: The comorbidity of @entity1 @entity2438 and @entity302 has been recognized for decades with little understanding of factors that increase risk. We show that two common @entity1 risk factors for @entity2438 (maternal stress and @entity4183 ), only when combined, result in severe @entity2438 -like behavior and @entity302 . The significance of this work is fourfold: (1) combinations of teratogens are required to assess true risk in @entity1 ; (2) maternal stress and @entity4183 , which are frequently combined in pregnant mothers, may be far more of a risk factor than previously appreciated; (3) astrogliosis may be a common mechanism for this syndrome; and (4) this first animal model of environmentally induced @entity2438 / @entity302 permits experimental investigation of cellular mechanisms and intervention strategies.
