How do maternal PTSD and alexithymia interact to impact maternal behavior?

Maternal interpersonal violence-related post-traumatic stress disorder (IPV-PTSD) is known to be associated with impairment of a mother's capacity to participate in mutual emotion regulation during her child's first years of life. This study tested the hypothesis that maternal difficulty in identifying feelings in self and other, as an important dimension of the construct of alexithymia, together with maternal IPV-PTSD, would be negatively associated with maternal sensitivity. Maternal sensitivity to child emotional communication is a marker of maternal capacity to engage in mutual regulation of emotion and arousal. Following diagnostic interviews and administration of the Toronto Alexithymia Scale, 56 mothers and their toddlers (ages 12-42 months) were filmed during free-play and separation/novelty-exposure. Observed maternal sensitivity was coded via the CARE-Index. Maternal IPV-PTSD severity, difficulty in identifying emotions, and lower socio-economic status were all associated with less maternal sensitivity, and also with more maternal controlling and unresponsive behavior on the CARE-Index.

Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool.

BACKGROUND: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. METHODOLOGY AND PRINCIPAL FINDINGS: We report a novel method for the long-term delivery of antibody fragments. We designed an allogenous immunoisolated implant consisting of polymer encapsulated myoblasts engineered to chronically release scFv antibodies targeted against the N-terminus of the Aß peptide. Following a 6-month intracerebral therapy we observed a significant reduction of the production and aggregation of the Aß peptide in the APP23 transgenic mouse model of Alzheimer's disease. In addition, functional assessment showed prevention of behavioral deficits related to anxiety and memory traits. CONCLUSIONS AND SIGNIFICANCE: The chronic local release of antibodies using immunoisolated polymer cell implants represents an alternative passive vaccination strategy in Alzheimer's disease. This novel technique could potentially benefit other diseases presently treated by local and systemic antibody administration.

Role of the amygdala in antidepressant effects on hippocampal cell proliferation and survival and on depression-like behavior in the rat.

The stimulation of adult hippocampal neurogenesis by antidepressants has been associated with multiple molecular pathways, but the potential influence exerted by other brain areas has received much less attention. The basolateral complex of the amygdala (BLA), a region involved in anxiety and a site of action of antidepressants, has been implicated in both basal and stress-induced changes in neural plasticity in the dentate gyrus. We investigated here whether the BLA modulates the effects of the SSRI antidepressant fluoxetine on hippocampal cell proliferation and survival in relation to a behavioral index of depression-like behavior (forced swim test). We used a lesion approach targeting the BLA along with a chronic treatment with fluoxetine, and monitored basal anxiety levels given the important role of this behavioral trait in the progress of depression. Chronic fluoxetine treatment had a positive effect on hippocampal cell survival only when the BLA was lesioned. Anxiety was related to hippocampal cell survival in opposite ways in sham- and BLA-lesioned animals (i.e., negatively in sham- and positively in BLA-lesioned animals). Both BLA lesions and low anxiety were critical factors to enable a negative relationship between cell proliferation and depression-like behavior. Therefore, our study highlights a role for the amygdala on fluoxetine-stimulated cell survival and on the establishment of a link between cell proliferation and depression-like behavior. It also reveals an important modulatory role for anxiety on cell proliferation involving both BLA-dependent and -independent mechanisms. Our findings underscore the amygdala as a potential target to modulate antidepressants' action in hippocampal neurogenesis and in their link to depression-like behaviors.

KAP1-mediated epigenetic repression in the forebrain modulates behavioral vulnerability to stress.

KAP1 is an essential cofactor of KRAB-zinc finger proteins, a family of vertebrate-specific epigenetic repressors of largely unknown functions encoded in the hundreds by the mouse and human genomes. Here, we report that KAP1 is expressed at high levels and necessary for KRAB-mediated repression in mature neurons of the mouse brain. Mice deleted for KAP1 in the adult forebrain exhibit heightened levels of anxiety-like and exploratory activity and stress-induced alterations in spatial learning and memory. In the hippocampus, a small number of genes are dysregulated, including some imprinted genes. Chromatin analyses of the promoters of two genes markedly upregulated in knockout mice reveal decreased histone 3 K9-trimethylation and increased histone 3 and histone 4 acetylation. We propose a model in which the tethering of KAP1-associated chromatin remodeling factors via KRAB-ZFPs epigenetically controls gene expression in the hippocampus, thereby conditioning responses to behavioral stress.

Stress amplifies memory for social hierarchy.

Individuals differ in their social status and societies in the extent of social status differences among their members. There is great interest in understanding the key factors that contribute to the establishment of social dominance structures. Given that stress can affect behavior and cognition, we hypothesized that, given equal opportunities to become either dominant or submissive, stress experienced by one of the individuals during their first encounter would determine the long-term establishment of a social hierarchy by acting as a two-stage rocket: (1) by influencing the rank achieved after a social encounter and (2) by facilitating and/or promoting a long-term memory for the specific hierarchy. Using a novel model for the assessment of long-term dominance hierarchies in rats, we present here the first evidence supporting such hypothesis. In control conditions, the social rank established through a first interaction and food competition test between two male rats is not maintained when animals are confronted 1 week later. However, if one of the rats is stressed just before their first encounter, the dominance hierarchy developed on day 1 is still clearly observed 1 week later, with the stressed animal becoming submissive (i.e., looser in competition tests) in both social interactions. Our findings also allow us to propose that stress potentiates a hierarchy-linked recognition memory between "specific" individuals through mechanisms that involve de novo protein synthesis. These results implicate stress among the key mechanisms contributing to create social imbalance and highlight memory mechanisms as key mediators of stress-induced long-term establishment of social rank.