Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa

MicroRNA expression profiling showed that the retina of mice carrying a rhodopsin mutation that leads to retinitis pigmentosa have notably different microRNA profiles from wildtype mice; further in silico analyses identified potential retinal targets for differentially regulated microRNAs

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants

Comparative expression of selected miRs in the retina, brain, and mouse platform

<p><b>Copyright information:</b></p><p>Taken from "Altered retinal microRNA expression profile in a mouse model of retinitis pigmentosa"</p><p>http://genomebiology.com/2007/8/11/R248</p><p>Genome Biology 2007;8(11):R248-R248.</p><p>Published online 22 Nov 2007</p><p>PMCID:PMC2258196.</p><p></p> Bars represent deviations from mean expression levels for each microRNA (miR) on a logscale in c57 retina (dark blue), c57 brain (light blue), and mouse platform (magenta). Relative expression of some known retinal miRs. Relative expression of miRs with novel retinal specificity. Panels a and b display data from miR microarray experiments. Quantitative real-time reverse transcription polymerase chain reaction (qPCR) validation of expression of selected miRs. Note that columns are in descending order of difference between retinal and platform expression; y-axes are to different scales; and bars for miR-181a in brain and miR-204 in mouse platform are missing in panel a because of incomplete data

Effect of acute and chronic lamotrigine on basal and stimulated extracellular 5-hydroxytryptamine and dopamine in the hippocampus of the freely moving rat

1. We have studied the effects of acute and chronic treatment with the anticonvulsant lamotrigine (LTG) on basal and stimulated extracellular 5-hydroxytryptamine (5-HT), dopamine (DA) and their metabolites in the hippocampus of freely moving rats using in vivo microdialysis. 2. Acute LTG (10 and 20 mg kg(−1)) decreased extracellular 5-HT, but had no effect on its metabolite 5-hydroxyindoleacetic acid (5-HIAA). Dialysate DA was also decreased by LTG as were its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). When transmitter release was stimulated by either 50 μM veratridine or 100 mM K(+), marked increases in the release of both transmitters occurred, but LTG was entirely without effect on this. 3. In chronic experiments, rats were dialysed after 2, 4, 7, 14 and 21 days of LTG treatment (5 mg kg(−1), twice daily). During this period a progressively different response to the drug was seen. After 2 days, basal extracellular 5-HT was significantly greater in treated rats than control rats. This effect persisted up to 14 days, but by 21 days 5-HT levels had returned to control values. 5-HIAA levels were unaltered and there was no effect of LTG on veratridine or K(+) stimulated 5-HT release. 4. Similarly, DA concentrations significantly increased after 2–7 days of LTG treatment, but returned and remained at basal values thereafter. During the treatment period LTG had no effect on extracellular DOPAC, but HVA followed a similar pattern to its parent transmitter. As with 5-HT, at no time point did LTG have any effect on stimulated DA release. 5. These neurochemical findings observed in these experiments are considered in relation to the use of LTG in bipolar disorder