The prion protein regulates glutamate-mediated Ca2+ entry and mitochondrial Ca2+ accumulation in neurons.

The cellular prion protein (PrPC) whose conformational misfolding leads to the production of deadly prions, has a still-unclarified cellular function despite decades of intensive research. Following our recent finding that PrPC limits Ca2+ entry via store-operated Ca2+ channels in neurons, we investigated whether the protein could also control the activity of ionotropic glutamate receptors (iGluRs). To this end, we compared local Ca2+ movements in primary cerebellar granule neurons and cortical neurons transduced with genetically encoded Ca2+ probes and expressing, or not expressing, PrPC Our investigation demonstrated that PrPC downregulates Ca2+ entry through each specific agonist-stimulated iGluR and after stimulation by glutamate. We found that, although PrP-knockout (KO) mitochondria were displaced from the plasma membrane, glutamate addition resulted in a higher mitochondrial Ca2+ uptake in PrP-KO neurons than in their PrPC-expressing counterpart. This was because the increased Ca2+ entry through iGluRs in PrP-KO neurons led to a parallel increase in Ca2+-induced Ca2+ release via ryanodine receptor channels. These data thus suggest that PrPC takes part in the cell apparatus controlling Ca2+ homeostasis, and that PrPC is involved in protecting neurons from toxic Ca2+ overloads.

Quantifying the recruitment challenges with couple-based interventions for cancer: applications to early-stage breast cancer.

OBJECTIVE: Despite mounting evidence supporting the use of psychosocial interventions to promote adaptation to cancer, enrolling participants into these interventions is challenging. This is particularly salient for couple-based interventions, and newer, more targeted recruitment strategies to increase enrollment are needed. However, there have been few published empirical studies focused specifically on recruitment-related variables associated with enrollment into these types of interventions. To better understand how to encourage participation in couple-based psychosocial interventions for cancer, we examined facilitating and impeding factors to enrollment into a couple-based intervention for women with early-stage breast cancer. METHOD: In this sample of 99 women diagnosed with early-stage breast cancer, patient demographic variables and method of approaching eligible patients were examined as predictors of enrollment into a randomized controlled trial comparing couple-based relationship enhancement with treatment as usual. RESULTS: Results indicated that women were more likely to enroll if they were contacted at home or at a follow-up medical appointment rather than when first diagnosed at a busy multidisciplinary clinic; they were also more likely to enroll the closer they lived to the research facility. CONCLUSIONS: In addition to decreasing participant burden, timing and setting of recruitment efforts may have important implications for enhancing participation rates in couple-based intervention studies for cancer.

Assessing disharmony and disaffection in intimate relationships: Revision of the Marital Satisfaction Inventory factor scales.

Previous research has identified 2 broad components of distress in intimate relationships: overt conflict, or disharmony, and emotional distance, or disaffection. Using confirmatory factor analysis, the authors derived 2 broadband scales of disharmony and disaffection from the Marital Satisfaction Inventory-Revised (D. K. Snyder, 1997), building upon previous measures of these constructs (D. K. Snyder & Regts, 1982) derived from the original instrument. The new scales demonstrated high internal consistency and test-retest reliability, as well as discriminative validity and convergent validity with independent criteria of relationship functioning. Distinct distributions of these scales in community and clinical samples suggested their complementary role in research on intimate relationships and assessment of couples in treatment.

Predictors of intimacy in couples' discussions of relationship injuries: an observational study.

The interpersonal process model of intimacy (H. T. Reis & P. Shaver, 1988) proposes that self-disclosure and empathic responding form the basis of intimate interactions. This study examined this model in 102 community couples who completed intimacy measures following videotaped discussions about relationship injuries occurring both within and outside the relationship. Observational assessments of self-disclosure and empathic responding, as well as their respective components, were related to self-reported ratings of post-interaction intimacy. Men's own disclosure and empathic responding predicted their feelings of intimacy, whereas women's intimacy was predicted by their partner's disclosure and empathic responding. Self-disclosure and empathic responding appear to be important behavioral determinants of intimate feelings, but the manner in which they influence intimacy differs according to gender.

The prion protein constitutively controls neuronal store-operated Ca(2+) entry through Fyn kinase.

The prion protein (PrP(C)) is a cell surface glycoprotein mainly expressed in neurons, whose misfolded isoforms generate the prion responsible for incurable neurodegenerative disorders. Whereas PrP(C) involvement in prion propagation is well established, PrP(C) physiological function is still enigmatic despite suggestions that it could act in cell signal transduction by modulating phosphorylation cascades and Ca(2+) homeostasis. Because PrP(C) binds neurotoxic protein aggregates with high-affinity, it has also been proposed that PrP(C) acts as receptor for amyloid-ß (Aß) oligomers associated with Alzheimer's disease (AD), and that PrP(C)-Aß binding mediates AD-related synaptic dysfunctions following activation of the tyrosine kinase Fyn. Here, use of gene-encoded Ca(2+) probes targeting different cell domains in primary cerebellar granule neurons (CGN) expressing, or not, PrP(C), allowed us to investigate whether PrP(C) regulates store-operated Ca(2+) entry (SOCE) and the implication of Fyn in this control. Our findings show that PrP(C) attenuates SOCE, and Ca(2+) accumulation in the cytosol and mitochondria, by constitutively restraining Fyn activation and tyrosine phosphorylation of STIM1, a key molecular component of SOCE. This data establishes the existence of a PrP(C)-Fyn-SOCE triad in neurons. We also demonstrate that treating cerebellar granule and cortical neurons with soluble Aß(1-42) oligomers abrogates the control of PrP(C) over Fyn and SOCE, suggesting a PrP(C)-dependent mechanizm for Aß-induced neuronal Ca(2+) dyshomeostasis.

Predicting 2-year marital satisfaction from partners' discussion of their marriage checkup.

This study tested whether the observed marital interactions of partners following a marriage checkup predicted marital satisfaction 2 years later. In addition, this study examined whether recommendations to pursue therapy predicted subsequent treatment seeking and whether changes in marital distress following the checkup remained stable over 2 years. Results suggest that the affective tone of a couple's interaction predicts later marital satisfaction. Further, receiving a treatment recommendation predicted subsequent treatment seeking for wives. Finally, support was found for the hypothesis that changes in marital distress are self-sustaining.

Current status and future directions in couple therapy.

Couple therapy research affirms that various approaches to couple treatment produce statistically and clinically significant improvement for a substantial proportion of couples in reducing overall relationship distress. Recent studies have extended these findings in indicating the effectiveness of couple-based interventions for a broad range of coexisting emotional, behavioral, or physical health problems in one or both partners. In contrast to these encouraging results, research also indicates that a sizeable percentage of couples fail to achieve significant gains from couple therapy or show significant deterioration afterward. Research on processes of change and predictors of treatment outcome in couple therapy provides preliminary evidence regarding factors potentially contributing to variable treatment response. The chapter concludes with 12 recommendations regarding future directions in couple therapy research and clinical training.