Evaluation of Affymetrix Gene Chip sensitivity in rat hippocampal tissue using SAGE analysis *

DNA microarrays are a powerful tool for monitoring thousands of transcript levels simultaneously. However, the use of DNA microarrays in studying the central nervous system faces several challenges. These include the detection of low-abundance transcripts in highly complex tissue as well as estimating relatively low-magnitude changes in transcript levels in response to experimental manipulation. Many transcripts important to brain function have low expression levels or are expressed in relatively few cells, making them difficult to detect in the complex background of brain tissue. The aim of the present study is to evaluate the sensitivity of Gene Chip detection of transcripts in brain by using results from serial analysis of gene expression (SAGE) studies. The results of this comparison indicate that Affymetrix Gene Chips, like SAGE, only reliably detect medium- to high-abundance transcripts and that detection of low-abundance transcripts, many of which have great relevance to biological function in brain, is inconsistent. Specifically, we estimate that Gene Chips reliably detect no more than 30% of the hippocampal transcriptome when using a gross hippocampal dissection as the source tissue. This report provides the first broad evaluation of Affymetrix Gene Chip sensitivity relevant to studying the brain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75717/1/j.1460-9568.2002.02097.x.pd

Earlier chronotype in patients with rheumatoid arthritis

Objectives: Rheumatoid arthritis (RA) patients show an earlier circadian rhythm (i.e. serum melatonin peaks earlier during the night, indicating an earlier timing of the internal circadian pacemaker). In the current study, we examined whether the chronotype, which is influenced by the circadian rhythm, is also earlier. In addition, we explored whether chronotype is related to disease activity and patient-reported outcomes. Methods: The chronotype (Munich Chronotype Questionnaire) of patients with RA (n = 121; mean age 60 years, 73% female) was compared with that of subjects from the general population (norm group; n = 1695) with a one-sample t test. In addition, we investigated chronotype in relation to disease activity (Disease Activity Score; DAS), reported morning stiffness, fatigue (Checklist Individual Strength), and health-related quality of life (RAND-36). Results: The chronotype of patients with RA was, on average, 23 min (95% CI, 15 to 31 min) earlier than that of the norm group (t(115) = − 5.901, p 0.05). Conclusion: As expected, chronotype was earlier in RA patients. However, in this correlational study, chronotype was not related to disease activity or patient-reported outcomes. An experimental study is needed to examine whether delaying the circadian rhythm has a positive influence on these outcomes. This insight could improve our understanding of the pathophysiology of RA and contribute to exploring new treatment possibilities.• This is the first study examining chronotype in patients with rheumatoid arthritis, and how chronotype relates to disease activity and patient-reported outcomes.• We found an earlier chronotype in patients with rheumatoid arthritis than in subjects from the general population.• In this correlational

Hippocampal CARP over-expression solidifies consolidation of contextual fear memories

The Doublecortin-Like Kinase (DCLK) gene is involved in neuronal migration during development. Through alternative splicing the DCLK gene also produces a transcript called Ca2+/calmodulin dependent protein kinase (CaMK)-related peptide (CARP) that is expressed exclusively during adulthood in response to neuronal activity. The function of CARP, however, is poorly understood. To study CARP function, we have generated transgenic mice with over-expression of the CARP transcript in, amongst other brain areas, the hippocampus. We aimed to characterize possible behavioral adaptations of these mice by using a Pavlovian fear conditioning approach. This type of fear conditioning, in which both the hippocampus and amygdala are critically involved, allows studying the formation and extinction of fear related memories. We here report on the behavioral adaptations of two distinct transgenic lines: one with high levels of CARP in the hippocampus and amygdala, whilst the other has high levels of CARP in the hippocampal formation, but not in the amygdala. We tested both mouse lines separately by comparing them to their wild-type littermate controls. We provide evidence suggesting consolidation of contextual fear memories is strengthened in mice of both transgenic lines. © 2010 Elsevier Inc

The microtubule associated protein doublecortin-like regulates the transport of the glucocorticoid receptor in neuronal progenitor cells

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