Chronic lithium administration down regulates transthyretin mRNA expression in rat choroid plexus

Transthyretin (TTR) accounts for a quarter of the protein content of ventricular cerebrospinal fluid (CSF) yet its exact role in the brain remains unknown. Patients with a diagnosis of depression have reduced CSF levels of TTR and the locus encoding the TTR gene has been implicated in a Danish pedigree of bipolar patients. Lithium, the major treatment for bipolar disorder in the UK, was subcutaneously infused into rats for 28 days in the form of lithium chloride using osmotic minipumps. In situ hybridizations using oligonucleotide probes targeted against the TTR transcript were performed on coronal brain sections. Lithium significantly reduced the level of transthyretin mRNA in the rat choroid plexus within the lateral and third ventricle. The down-regulation was confirmed using semi-quantitative reverse transcription PCR on dissected brain tissue. Recent studies in mice suggest that the TTR gene is implicated in depression-like behavior therefore this effect of lithium may be relevant to its use as a mood stabilizer or an adjuvant to antidepressant drugs

Mobile and cordless telephones, serum transthyretin and the blood-cerebrospinal fluid barrier: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Whether low-intensity radiofrequency radiation damages the blood-brain barrier has long been debated, but little or no consideration has been given to the blood-cerebrospinal fluid barrier. In this cross-sectional study we tested whether long-term and/or short-term use of wireless telephones was associated with changes in the serum transthyretin level, indicating altered transthyretin concentration in the cerebrospinal fluid, possibly reflecting an effect of radiation.</p> <p>Methods</p> <p>One thousand subjects, 500 of each sex aged 18–65 years, were randomly recruited using the population registry. Data on wireless telephone use were assessed by a postal questionnaire and blood samples were analyzed for serum transthyretin concentrations determined by standard immunonephelometric techniques on a BN Prospec^®instrument.</p> <p>Results</p> <p>The response rate was 31.4%. Logistic regression of dichotomized TTR serum levels with a cut-point of 0.31 g/l on wireless telephone use yielded increased odds ratios that were statistically not significant. Linear regression of time since first use overall and on the day that blood was withdrawn gave different results for males and females: for men significantly higher serum concentrations of TTR were seen the longer an analogue telephone or a mobile and cordless desktop telephone combined had been used, and in contrast, significantly lower serum levels were seen the longer an UMTS telephone had been used. Adjustment for fractions of use of the different telephone types did not modify the effect for cumulative use or years since first use for mobile telephone and DECT, combined. For women, linear regression gave a significant association for short-term use of mobile and cordless telephones combined, indicating that the sooner blood was withdrawn after the most recent telephone call, the higher the expected transthyretin concentration.</p> <p>Conclusion</p> <p>In this hypothesis-generating descriptive study time since first use of mobile telephones and DECT combined was significantly associated with higher TTR levels regardless of how much each telephone type had been used. Regarding short-term use, significantly higher TTR concentrations were seen in women the sooner blood was withdrawn after the most recent telephone call on that day.</p