Oxytocin modulates the link between adult attachment and cooperation through reduced betrayal aversion

An experiment examined whether and how the relationship between individual differences in social attachment and cooperation is modulated by brain oxytocin, a neuropeptide implicated both in parent-child bonding, and in social approach. Healthy males completed a validated attachment style measure, received intranasal oxytocin or placebo, and privately chose between cooperation and non-cooperation in an incentivized social dilemma with an anonymous stranger. Attachment anxiety--the tendency to fear rejection by others--had few effects and was not modulated by oxytocin. However, oxytocin interacted with attachment avoidance--the tendency to fear dependency and closeness in interpersonal relations. Especially among participants high rather than low in attachment avoidance, oxytocin reduced betrayal aversion, and increased trust and cooperation compared to placebo. Effects of attachment avoidance and oxytocin on cooperation were mediated by betrayal aversion, and not by affiliation tendencies.     

Victims of rape show increased cortisol responses to trauma reminders: a study in individuals with war- and torture-related PTSD

Studies investigating cortisol responses to trauma-related stressors in patients with posttraumatic stress disorder (PTSD) have yielded inconsistent results, demonstrating that cortisol responses were enhanced or unaffected when confronted with trauma reminders. This study investigated the effect of the type of trauma experienced on both salivary and plasma cortisol responses during confrontation with trauma-related material. Participants were 30 survivors of war and torture, with and without rape among the traumatic events experienced. Participants of both groups (raped vs. non-raped) fulfilled DSM-IV criteria of PTSD. Plasma and salivary cortisol levels were measured at three time points during a standardized clinical interview: once before and twice after assessing individual traumatic experiences. Results show that groups did not differ in basal plasma and salivary cortisol levels. However, differential salivary cortisol responses were observed in PTSD patients who had been raped compared to those who had not been raped (p<.05) but had experienced an equal number of traumatic events and showed equally high PTSD symptom severity. Whereas salivary cortisol levels decreased in the course of the interview for the group with no past experience of rape (p<.05), those PTSD patients who had been raped showed a significant cortisol increase when reminded of their traumatic events (p<.001). This effect was not found in plasma cortisol. Our results indicate that the type of traumatic stress experienced contributes to cortisol responses during the confrontation with trauma-related material. We hypothesize, that the nearness of the perpetrator during the traumatic event might shape later psychophysiological responding to trauma reminders.     

Visual assessment of dopaminergic degeneration pattern in <Superscript>123</Superscript>I-FP-CIT SPECT differentiates patients with atypical parkinsonian syndromes and idiopathic Parkinson's disease

The aim of this study was to investigate whether visual assessment of ¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (¹²³I-FP-CIT) single photon emission computed tomography (SPECT) in addition to quantitative analyses can help to differentiate idiopathic Parkinson's disease (PD) from atypical parkinsonian syndromes (APS). From a consecutive series of patients examined with ¹²³I-FP-CIT SPECT (n = 190) over a three-year period we identified 165 patients with a clinical diagnosis of PD (n = 120) or APS (n = 45). ¹²³I-FP-CIT SPECT results were analysed visually and quantitatively and compared for PD and APS and for the subgroup of patients with early PD and APS (disease duration <5 years). According to predefined visual patterns of dopaminergic degeneration the results were graded as normal (grade 5) or abnormal (grade 1–4), distinguishing a posterior-anterior degeneration pattern (“egg shape”) from a global and severe degeneration pattern (“burst striatum”). Visual assessment of ¹²³I-FP-CIT SPECT showed significant different dopaminergic degeneration patterns for PD and APS patients. A grade 1 (“burst striatum”) degeneration pattern was predominantly associated with APS patients. In contrast to that, a grade 2 (egg shape) degeneration pattern was the characteristic finding in PD patients. In a subgroup of patients with early disease, visual assessment with identification of the burst striatum degeneration pattern provided 90% positive predictive value and 99% specificity for the diagnosis of APS. Quantitative analysis of striatal binding ratios failed to depict these different degeneration patterns in PD and APS patients. Visual assessment of the pattern of dopaminergic loss in ¹²³I-FP-CIT SPECT shows different patterns of dopaminergic degeneration for PD and APS patients. Therefore, it could provide valuable information to distinguish APS from PD patients, especially in early stages of disease. Within the first 5 years of disease, the occurrence of a burst striatum degeneration pattern has a high positive predictive value of APS.     

Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis

Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence of their intrathecal production in conjunction with the white cell count in the CSF and typical clinical symptoms is the traditional diagnostic gold standard of Lyme neuroborreliosis (LNB). Few data are available on the CSF lactate concentration in European adults with the diagnosis of acute LNB. The objective of the study was to investigate the CSF changes during acute LNB. Routine CSF parameters [leukocyte count, protein, lactate and albumin concentrations, CSF/serum quotients of albumin (Q_Alb), IgG, IgA and IgM, and oligoclonal IgG bands] and the Borrelia burgdorferi (BB)-specific antibody index were retrospectively studied in relation to the clinical presentation in patients diagnosed with acute LNB. A total of 118 patients with LNB were categorized into the following groups according to their symptoms at presentation; group 1: polyradiculoneuritis (Bannwarth’s syndrome), group 2: isolated facial palsy and group 3: predominantly meningitic course of the disease. In addition to the CSF of patients with acute LNB, CSF of 19 patients with viral meningitis (VM) and 3 with neurolues (NL) were analyzed. There were 97 patients classified with definite LNB, and 21 as probable LNB. Neck stiffness and fever were reported by 15.3% of patients. Most of these patients were younger than 50 years. Polyradiculoneuritis was frequently found in patients older than 50 years. Lymphopleocytosis was found in all patients. Only 5 patients had a CSF lactate ≥3.5 mmol/l, and the mean CSF lactate level was not elevated (2.1 ± 0.6 mmol/l). The patients with definite LNB had significantly higher lactate levels than patients with probable LNB. Elevated lactate levels were accompanied by fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF protein concentration and CSF/serum quotients of albumin than LNB patients. In acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts. In contrast to infections by other bacteria, CSF lactate was lower than 3.5 mmol/l in all but 5 patients. The CSF findings did not differ between polyradiculoneuritis, facial palsy, and meningitis. The CSF in LNB patients strongly differed from CSF in VM patients with respect to protein concentration and the CSF/serum albumin quotient.     

Automatic detection of childhood absence epilepsy seizures: toward a monitoring device

Automatic detections of paroxysms in patients with childhood absence epilepsy have been neglected for several years. We acquire reliable detections using only a single-channel brainwave monitor, allowing for unobtrusive monitoring of antiepileptic drug effects. Ultimately we seek to obtain optimal long-term prognoses, balancing antiepileptic effects and side effects. The electroencephalographic appearance of paroxysms in childhood absence epilepsy is fairly homogeneous, making it feasible to develop patient-independent automatic detection. We implemented a state-of-the-art algorithm to investigate the performance of paroxysm detection. Using only a single scalp electroencephalogram channel from 20 patients with a total of 125 paroxysms >2 seconds, 97.2% of paroxysms could be detected with no false detections. This result leads us to recommend further investigations of tiny, one-channel electroencephalogram systems in an ambulatory setting.     

Activation of KCNN3/SK3/KCa2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia

In neurons, small‐conductance calcium‐activated potassium (KCNN/SK/K_Ca2) channels maintain calcium homeostasis after N‐methyl‐D ‐aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/K_Ca2 channels in non‐neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/K_Ca2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N‐cyclohexyl‐N‐[2‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐6‐methyl‐4‐pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/K_Ca2 channels, significantly reduced LPS‐stimulated activation of microglia in a concentration‐dependent manner. The general KCNN/SK/K_Ca2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/K_Ca2 channel activation affected the changes of intracellular calcium levels, [Ca²⁺]_i,, in microglial cells. Our data show that LPS‐induced elevation of [Ca²⁺]_i was attenuated following activation of KCNN2/3/K_Ca2.2/K_Ca2.3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/K_Ca2 channel subtypes to identify which particular channel subtype mediated the observed anti‐inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/K_Ca2.3 channels, but not KCNN2/SK2/K_Ca2.2 channel inhibition, reversed the CyPPA‐effects on LPS‐induced microglial proliferation. These findings revealed that KCNN3/SK3/K_Ca2.3 channels can modulate the LPS‐induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/K_Ca2.3 channels may serve as a therapeutic target for reducing microglial activity and related inflammatory responses in the central nervous system. © 2012 Wiley Periodicals, Inc.     

Impact of vegf on astrocytes: analysis of gap junctional intercellular communication, proliferation, and motility

The purpose of the present study was to investigate the effects of vascular endothelial growth factor (VEGF) on gap junctional intercellular communication (GJIC), cell proliferation, and cell dynamics in primary astrocytes. VEGF is known as a dimeric polypeptide that potentially binds to two receptors, VEGFR-1 and VEGFR-2, however many effects are mediated by VEGFR-2, for example, actin polymerization, forced cell migration, angiogenesis, and cell proliferation. Recently it has been shown that in case of hypoxia, ischemia or injury VEGF is upregulated to stimulate angiogenesis and cell proliferation. Besides this, VEGF reveals a potent therapeutical target for averting tumor vascularization, emerging in bevacizumab, the first humanized anti-VEGF-A antibody for treating recurrent Glioblastoma multiforme. To expand our knowledge about VEGF effects in glial cells, we cultivated rat astrocytes in medium containing VEGF for 1 and 2 days. To investigate the effects of VEGF on GJIC, we microinjected neurobiotin into a single cell and monitored dye-spreading into adjacent cells. These experiments showed that VEGF significantly enhances astrocytic GJIC compared with controls. Cell proliferation measured by BrdU-labeling also revealed a significant increase of astrocytic mitose rates subsequent to 1 day of VEGF exposure, whereas longer VEGF treatment for 2 days did not have additive effects. To study cell-dynamics of astrocytes subsequent to VEGF treatment, we additionally transfected astrocytes with LifeAct-RFP. Live-cell imaging and quantitative analysis of these cells with aid of confocal laser scanning microscopy revealed higher process movement of VEGF-treated astrocytes. In conclusion, VEGF strongly affects cell proliferation, GJIC, and motility in astrocytes.