Trafficking of AMPA receptors (AMPARs) is regulated by specific interactions of the subunit intracellular C-terminal domains (CTDs) with other proteins, but the mechanisms involved in this process are still unclear. We have found that the GluR1 CTD binds to cGMP-dependent protein kinase II (cGKII) adjacent to the kinase catalytic site. Binding of GluR1 is increased when cGKII is activated by cGMP. cGKII and GluR1 form a complex in the brain, and cGKII in this complex phosphorylates GluR1 at S845, a site also phosphorylated by PKA. Activation of cGKII by cGMP increases the surface expression of AMPARs at extrasynaptic sites. Inhibition of cGKII activity blocks the surface increase of GluR1 during chemLTP and reduces LTP in the hippocampal slice. This work identifies a pathway, downstream from the NMDA receptor (NMDAR) and nitric oxide (NO), which stimulates GluR1 accumulation in the plasma membrane and plays an important role in synaptic plasticity.
A minority of parents met criteria for PGD and depression, however, almost half the sample was experiencing significant separation distress associated with persistent longing and yearning for their child. Time since death is a significant predictor of parental psychological distress. This study also highlights the importance of end-of-life factors in parents' long-term adjustment and the need for optimal palliative care to ensure the best possible outcomes for parents.
We piloted a novel parent-targeted intervention, Take A Breath (TAB), for parents of children diagnosed with a life-threatening illness (LTI) with the aim of reducing parental distress. Parents were assisted to adapt to their child's diagnosis, treatment, and recovery via TAB's combined acceptance and commitment therapy (ACT) and problem-solving skills training (PSST) approach. Participants were 11 parents of children with a diagnosis of cancer, or who had life-saving cardiac surgery at least 4 months prior. Parents completed questionnaires at pre, post, and 6-month follow-up assessing parent posttraumatic stress symptoms (PTSS), the emotional impact of the child's LTI (e.g., feelings of uncertainty, guilt and sorrow, emotional resources), and psychological elements targeted by the intervention (parental psychological flexibility and mindfulness). Parents reported significant reductions in PTSS and emotional impact from their child's LTI, along with significant improvements in parental psychological flexibility and mindfulness. Effect sizes were medium to large, and improvements were maintained at 6-month follow-up. Our pilot indicates the TAB intervention has promise for preventing or reducing parental distress associated with child LTI and warrants more rigorous evaluation. Although preliminary, these findings suggest that targeting parents' subjective perceptions of their child's LTI may be an effective approach to reducing parental distress. Our results also indicate the potential for such an approach to be adopted across diverse child diagnoses in the acute pediatric setting. Further, our findings provide early indications that ACT combined with PSST is an appropriate therapeutic approach within this context.
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