CSF-hypocretin-1 levels in patients with major depressive disorder compared to healthy controls.

Depressive patients exhibit symptoms of impaired regulation of wakefulness with hyperarousal and agitation as well as difficulties to falling asleep and preserving sleep continuity. Changes in hypocretin (hcrt) levels as polypeptides with impact on arousal and sleep-wake-regulation have been discussed in affective disorders but have not been investigated in patients with solely unipolar depression in comparison to healthy controls. In the present study, cerebrospinal fluid (CSF) levels of hcrt-1 for the first time were analyzed in patients with major depressive disorder (MDD) without psychiatric comorbidities and compared with levels in healthy controls. In 17 inpatients with MDD (mean Hamilton Depression Rating Scale 13.9 ± 7.4) and 10 healthy controls, CSF-hcrt-1 levels were measured using a fluorescence immunoassay (FIA). The mean hcrt-1 CSF levels in patients with MDD (74.3 ± 17.8pg/ml) did not differ compared to that of healthy controls (82.8 ± 22.1pg/ml). Hcrt-1 levels did not correlate with the severity of depressive episode, the symptoms of depression or the number of episodes. Although autonomic and neurohumoral signs of hyperarousal are common in MDD, hcrt-1 levels in CSF were not found to be altered in MDD compared to healthy controls. Whether hcrt-1 levels are altered in depressive patients exhibiting impaired vigilance regulation has to be investigated in further studies combining measures of CSF-hcrt-1 with electroencephalography.

Reduction and expansion of the glutamine synthetase expressing zone in livers from tetracycline controlled TGF-beta1 transgenic mice and multiple starved mice.

BACKGROUND/AIMS: To learn more about tissue remodelling in fibrotic livers of tetracycline-controlled TGF-beta1 transgenic mice (TGF-beta1-on-mice) and during regeneration after removal of the fibrotic stimulus (off-mice), we investigated the expression of glutamine synthetase (GS), an exclusive pericentrally expressed enzyme. METHODS: GS was localised immunohistochemically and quantified by real-time RT-PCR and enzymatic activity measurement. Apoptosis in livers of TGF-beta1-on-mice was demonstrated by in situ apoptosis detection kit (TUNEL reaction). RESULTS: Livers of TGF-beta1-on-mice harbour a reduced number of GS-positive hepatocytes and expression of GS is downregulated, while multiple starved mice serving as controls for malnutrition during TGF-beta1 exposure surprisingly showed an impressive amplification of GS-positive hepatocytes. Apoptotic events were frequent around central veins in livers of TGF-beta1-on-mice, while in multiple induced mice apoptosis was dominant around all vessels and weak in midzonal areas. During regeneration from fibrosis, control levels were regained within 21 days. Beta-catenin was dislocated from plasma membrane to cytoplasm exclusively in pericentral hepatocytes during a short time slot after a unique expression of TGF-beta1. CONCLUSIONS: Reduction of GS in TGF-beta1-on-mice results from apoptosis of GS-positive hepatocytes rather than downregulation of GS expression. Beta-catenin seems involved in the recovery of GS-positive hepatocytes.