The chemokine CXCL10 modulates excitatory activity and intracellular calcium signaling in cultured hippocampal neurons

In this study, we provide evidence for direct modulatory effects of the chemokine, CXCL10, on the physiology of hippocampal neurons maintained in primary culture. CXCL10 elicited a rise in intracellular Ca2+ and enhanced both spontaneous and evoked electrical activity of hippocampal neurons. CXCL10-induced elevations in intracellular Ca2+ were associated with an increase in neuronal firing and an alteration in the relationship between the evoked Ca2+ signal and neuronal activity. The effects of CXCL10 were not accompanied by a shift in resting membrane potential (RMP) or input resistance. Expression of the CXCR3 chemokine receptor supports a direct effect of CXCL10 on hippocampal neurons.     

Genotype determines phenotype in experimental Lyme borreliosis

Borrelia burgdorferi sensu lato, the causative organism of Lyme borreliosis, is a heterogeneous group of spirochetes, consisting of at least three pathogenic species. To test the hypothesis that the genetic heterogeneity is the reason for the clinical differences, we investigated whether the experimental disease induced by European isolates is different from that induced by American isolates. Two American isolates of species B. burgdorferi sensu stricto were compared with three European isolates, two of species B. garinii, and one of species B. afzelii. The patterns of infection, immunity, and inflammation induced by the different species was distinctive. Inflammatory cells and levels of antibody in B. garinii- and B. afzelii-infected animals were lower than in B. burgdorferi s.s.-infected animals, whereas levels of spirochetal infection in the skin and nervous system were higher in the former group of animals. These data demonstrate that B. burgdorferi s.s. strains are more infective and inflammatory, whereas B. garinii and B. afzelii strains can survive the adaptive immune response to a greater degree and persist at greater numbers in the skin and nervous system. The results explain to a large extent the disparities between LNB in humans in the United States and Europe.     

An fMRI investigation of speech and tone segmentation

Recent research strongly indicates that phonological tasks activate a subregion of the inferior frontal gyrus. The purpose of the present fMRI study was to investigate the extent to which activation of this region during phonological processing is due to speech processes per se such as articulatory recoding or to other cognitive task demands such as working memory. Thus, we compared activation patterns during segmentation of speech and tone sequences to a tone discrimination task. In particular, participants performed same/different judgments on pairs of words, pseudowords, and tone sequences that required segmentation of a continuous acoustic signal as well as tone pairs that did not require segmentation. Accuracy and reaction time data showed that speech and tone sequence segmentation conditions patterned more similarly to each other than to tone discrimination pairs. Analyses of group data revealed strong activation of the region at the border of the left inferior and middle frontal gyrus for all three segmentation conditions compared to tone discrimination, but no consistent differences were observed when word and pseudoword segmentation were directly contrasted. Analyses of individual subjects indicated that a large number of participants activated a small area of the middle frontal gyrus during the speech conditions compared to the sequences. These results suggest that a significant portion of active frontal areas is recruited for extracting acoustic information and maintaining it in memory for decision. However, some regions at the border of the inferior/middle frontal gyrus may be unique to speech segmentation.     

Neurochemical imaging of dementias

Neurochemical imaging is one of the most established "molecular" imaging techniques. There have been tremendous efforts expended to develop radioligands specific to each neurochemical system. Investigational applications of neurochemical imaging in dementing disorders are extensive. Cholinergic, dopaminergic, and serotonergic systems, as well as benzodiazepine receptors, opioid receptors, and glutamatergic receptors have been imaged in Alzheimer disease and other dementing disorders. These investigations have provided important insights into disease processes in living human patients. The clinical diagnostic use of neurochemical imaging for dementing disorders is currently limited, but this technique is used to help develop therapeutic drugs at multiple levels.     

Inhibition of mixed lineage kinase 3 attenuates MPP+-induced neurotoxicity in SH-SY5Y cells

5-HT(1B) autoreceptors regulate serotonin release from terminals of dorsal raphe nucleus (DRN) projections. Due to postsynaptic 5-HT(1B) receptors in DRN terminal fields, it has not previously been possible to manipulate 5-HT(1B) autoreceptor activity without also changing 5-HT(1B) heteroreceptor activity. We have developed a viral gene transfer strategy to express epitope-tagged 5-HT(1B) and green fluorescent protein in vivo, allowing us to increase 5-HT(1B) expression in DRN neurons. We have shown that increased 5-HT(1B) autoreceptor expression reduced anxiety in unstressed animals but increased anxiety following inescapable stress. These findings suggest that effects of increased 5-HT(1B) autoreceptor expression are dependent on stress context. To better understand the mechanisms underlying these observations, we have used fear-potentiated startle (FPS). FPS is especially sensitive to the activity of the amygdala, which shares reciprocal connections with DRN. In the absence of an inescapable stressor, increased 5-HT(1B) autoreceptor expression attenuated FPS response compared with animals injected with a virus expressing only green fluorescent protein. Administration of the 5-HT(1B) antagonist SB224289 (5 mg/kg i.p.) before startle testing blocked the effects of increased 5-HT(1B) autoreceptor expression. Since SB224289 had no effect on FPS in the absence of viral gene transfer, these results suggest that the antagonist reversed the behavioral effects of increased 5-HT(1B) autoreceptor expression through blockade of transgenic receptors. When tested 24 h following water-restraint stress, animals with increased 5-HT(1B) autoreceptors demonstrated restoration of robust FPS response. These results extend our previous studies and suggest explanations for the complex relationship between 5-HT(1B) autoreceptor expression, stress, and anxiety behavior.     

Time-dependent reduction in Abeta levels after intracranial LPS administration in APP transgenic mice

Inflammation has been argued to play a primary role in the pathogenesis of Alzheimer's disease (AD). Lipopolysaccharide (LPS) activates the innate immune system, triggering gliosis and inflammation when injected in the central nervous system. In studies described here, APP transgenic mice were injected intrahippocampally with 4 or 10 microg of LPS and evaluated 1, 3, 7, 14, or 28 days later. Abeta load was significantly reduced at 3, 7, and 14 days but surprisingly returned near baseline 28 days after the injection. No effects of LPS on congophilic amyloid deposits could be detected. LPS also activated both microglia and astrocytes in a time-dependent manner. The GFAP astrocyte reaction and the Fcgamma receptor microglial reaction peaked at 7 days after LPS injection, returning to baseline by 2 weeks postinjection. When stained for CD45, microglial activation was detected at all time points, although the morphology of these cells transitioned from an ameboid to a ramified and bushy appearance between 7 and 14 days postinjection. These results indicate that activation of brain glia can rapidly and transiently clear diffuse Abeta deposits but has no effect on compacted fibrillar amyloid.     

Who is portrayed in psychotropic drug advertisements?

The purpose of our study was to determine who is portrayed in psychotropic drug advertisements across time in three national psychiatric journals. All psychotropic drug advertisements portraying people were collected from the American Journal of Psychiatry, the British Journal of Psychiatry, and the Canadian Journal of Psychiatry at three time intervals (1981, 1991, and 2001). The advertisements were classified according to patient demographics, patient portrayal, and product information. Chi-square analysis was used to test for statistically significant associations among the variables. Fifty-seven percent of the psychotropic drug advertisements featured women, and 88% portrayed white patients. Statistically significant associations were detected between gender and the setting in which the patient was portrayed (chi(2) = 13.54, df = 3, p < 0.004), and gender and role (chi(2) = 29.41, df = 3, p < 0.001). Disproportionate gender representation was most notable in the 2001 time interval in the American Journal of Psychiatry. Women and white patients were overrepresented compared with psychiatric epidemiologic data in all three countries. The effect of these advertisements on physician perception, diagnosis, and prescribing is unknown but may be substantial. Future advertisements for psychotropic drugs should seek more balanced representations of gender and race.     

A self-psychology approach to narcissistic personality disorder: a nursing reflection

TOPIC: The use of Heinz Kohut's self-psychology perspective in understanding and providing care for patients with narcissistic personality disorder (NPD). PURPOSE: To describe how nurses can apply the self-psychology perspective as a way to understand the development of self for individuals with NPD and to enhance the therapeutic relationship between the nurse and patient with NPD. SOURCES: Theoretical literature; the author's clinical experience. CONCLUSIONS: Self-psychology provides nurses with a theoretical perspective that can enhance the interpersonal relationship between the nurse and patient with NPD.     

Violent lives of women: critical points for intervention--phase I focus groups

PROBLEM: To identify critical developmental periods, experiences, and events in women's lives associated with violence to guide a larger study. METHODS: Two focus groups of 10 women each (N = 20) were conducted to determine the critical times when girls and women might be exposed to violence. FINDINGS: Broad themes in the data were developmental periods, abusers, staying in the relationship, leaving the relationship, parenting, and living with violence. The women in these focus groups clearly identified times of increased risk for violence in their lives: establishing intimate relationships, pregnancy, childrearing years, and times when substance abuse is occurring. CONCLUSIONS: While clinicians should be vigilant for the presence of domestic violence with all clients, it is important to know when a woman experiences increased risk for violence. The findings indicate a need for education for communities, those who provide care for women and children, and people in whom victims may confide.