Dendritic Spine Density is Increased in Arcadlin-deleted Mouse Hippocampus.

The neural network undergoes remodeling in response to neural activity and interventions, such as antidepressants. Cell adhesion molecules that link pre- and post-synaptic membranes are responsible not only for the establishment of the neural circuitry, but also for the modulation of the strength of each synaptic connection. Among the various classes of synaptic cell adhesion molecules, a non-clustered protocadherin, Arcadlin/Paraxial protocadherin/Protocadherin-8 (Acad), is unique in that it is induced quickly in response to neural activity. Although the primary structure of Arcadlin implies its cell adhesion activity, it weakens the adhesion of N-cadherin. Furthermore, Arcadlin reduces the dendritic spine density in cultured hippocampal neurons. In order to gain an insight into the function of Arcadlin in the brain, we examined the dendritic morphologies of the hippocampal neurons in Acad-/- mice. Acad-/- mice showed a higher spine density than wild-type mice. Following an electroconvulsive seizure (ECS), which strongly induces Arcadlin in the hippocampus, the spine density gradually decreased for 8 h. ECS did not reduce the spine density of CA1 apical dendrites in Acad-/- mice. Daily intraperitoneal injection of the antidepressant fluoxetine (25 mg/kg/day) for 18 days resulted in the induction of Arcadlin in the hippocampus. This treatment reduced spine density in the dentate gyrus and CA1. Chronic fluoxetine treatment did not suppress spine density in Acad-/- mice, suggesting that fluoxetine-induced decrease in spine density is largely due to Arcadlin. The present findings confirm the spine-repulsing activity of Arcadlin and its involvement in the remodeling of hippocampal neurons in response to antidepressants.

Iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging of multiple myeloma: initial clinical efficiency results.

OBJECTIVES: To evaluate the effectiveness of the iterative decomposition of water and fat with echo asymmetric and least-squares estimation (IDEAL) MRI to quantify tumour infiltration into the lumbar vertebrae in myeloma patients without visible focal lesions. METHODS: The lumbar spine was examined with 3 T MRI in 24 patients with multiple myeloma and in 26 controls. The fat-signal fraction was calculated as the mean value from three vertebral bodies. A post hoc test was used to compare the fat-signal fraction in controls and patients with monoclonal gammopathy of undetermined significance (MGUS), asymptomatic myeloma or symptomatic myeloma. Differences were considered significant at P < 0.05. The fat-signal fraction and ß(2)-microglobulin-to-albumin ratio were entered into the discriminant analysis. RESULTS: Fat-signal fractions were significantly lower in patients with symptomatic myelomas (43.9 ±19.7%, P < 0.01) than in the other three groups. Discriminant analysis showed that 22 of the 24 patients (92%) were correctly classified into symptomatic or non-symptomatic myeloma groups. CONCLUSIONS: Fat quantification using the IDEAL sequence in MRI was significantly different when comparing patients with symptomatic myeloma and those with asymptomatic myeloma. The fat-signal fraction and ß(2)-microglobulin-to-albumin ratio facilitated discrimination of symptomatic myeloma from non-symptomatic myeloma in patients without focal bone lesions. KEY POINTS: • A new magnetic resonance technique (IDEAL) offers new insights in multiple myeloma. • Fat-signal fractions were lower in patients with symptomatic myelomas than in those with asymptomatic myelomas. • The ß2-microglobulin-to-albumin ratio also aided discrimination of symptomatic myeloma. • The fat-signal fraction may provide information about the myeloma cell mass.

Multiple myeloma: microstructural analysis of lumbar trabecular bones in patients without visible bone lesions--preliminary results.

PURPOSE: To evaluate the accuracy of trabecular analysis of the lumbar spine by using multidetector computed tomography (CT) in differentiating multiple myeloma patients without spinal fractures from control subjects. MATERIALS AND METHODS: This retrospective single-institution study was approved by the institutional review board, with a waiver of informed consent. Spinal microarchitecture was examined by using 64-detector row CT in 29 patients with multiple myeloma and 51 control subjects. The patients were 13 men and 16 women (mean ages, 71.1 and 69.2 years, respectively). By using multidetector CT data, eight parameters were calculated for the L3 vertebral trabeculae with a three-dimensional image analysis system. The χ(2) test was used to select a preliminary set of predictors for multiple myeloma. A multivariable generalized linear model was constructed to identify parameters that could be used to differentiate between patients and controls. Parameters with findings of P < .05 were included in the multivariable model. RESULTS: Generalized linear models showed that mean trabecular thickness (TbTh) (patients, 703.7 µm ± 46.7 [standard deviation]; controls, 661.1 µm ± 35.7) and fractal dimension (FD) (patients, 2.23 ± 0.24; controls, 2.41 ± 0.15) in men (P = .05 and .03, respectively) and degree of anisotropy (DA) (patients, 1.63 ± 0.23; controls, 1.38 ± 0.10) in women (P = .02) had significant effects in differentiation between patients and controls. CONCLUSION: Significant differences were observed in spinal microarchitecture between control subjects and multiple myeloma patients without pathologic fractures. Independent predictors of multiple myeloma included TbTh and FD in male patients and DA in female patients.

Anxiety, reactivity, and social stress-induced cortisol elevation in humans.

OBJECTIVES: Traditionally, it has been hypothesized that highly anxious/emotionally reactive subjects may have exaggerated social stress response. We examined the relationship between self-reported anxiety, emotional reactivity, and social stress response. METHODS: We investigated the relationship between personality scales of trait-state anxiety, subjective autonomic reactivity, and salivary cortisol levels before and after social stress exposure (Trier Social Stress Test) in 20 men. RESULTS: Significant positive correlations between anxiety, subjective autonomic reactivity, and basal cortisol levels were observed, while neither anxiety nor subjective autonomic reactivity was correlated with social stress-induced cortisol elevation. CONCLUSIONS: The present results indicate (i) subjects with higher degrees of trait anxiety/subjective autonomic reactivity have higher basal cortisol levels, and (ii) in contrast to the traditional view, anxious personality is not strongly associated with exaggerated cortisol response to social stress.

Interpersonal trust and social stress-induced cortisol elevation.

A neuroendocrine correlate of interpersonal trust is relatively unknown. We investigated the relationship between an interpersonal trust-related personality (General Trust Scale) and cortisol elevation induced by social stress in 20 men. Spearman's rank order correlation analysis revealed a significant negative correlation between social stress-induced cortisol elevation and General Trust Scale. The present results indicate subjects with higher degrees of interpersonal trust have lower levels of neuroendocrine response to social stress.

Social stress-induced cortisol elevation acutely impairs social memory in humans.

Although stress is known to affect the memory process, little has been elucidated regarding its effect on social memory. In this study, 30 subjects' social memory (face-name association memory) performance was tested. Twenty subjects were exposed to social stress with a subsequent test of social memory, while the remaining ten subjects served as controls. Free cortisol was determined via saliva samples taken before and after the social stress exposure. Because stress hormones might have biphasic actions on neurons, we separated the subjects with cortisol elevations between high and low responders. The high responders had significantly impaired social memory. Furthermore, we observed a negative relation between social stress-induced cortisol elevation and social memory. These results indicate that social stress acutely impairs social memory.