RESUMEN
Serotonin (5-hydroxytryptamine, 5-HT) as well as noradrenaline (NA) are key modulators of various fundamental brain functions including the control of appetite. While manipulations that alter brain serotoninergic signaling clearly affect body weight, studies implicating 5-HT transporters and NA transporters (5-HTT and NAT, respectively) as a main drug treatment target for human obesity have not been conclusive. The aim of this positron emission tomography (PET) study was to investigate how these central transporters are associated with changes of body weight after 6 months of dietary intervention or Roux-en-Y gastric bypass (RYGB) surgery in order to assess whether 5-HTT as well as NAT availability can predict weight loss and consequently treatment success. The study population consisted of two study cohorts using either the 5-HTT-selective radiotracer [11C]DASB to measure 5-HTT availability or the NAT-selective radiotracer [11C]MRB to assess NAT availability. Each group included non-obesity healthy participants, patients with severe obesity (body mass index, BMI, >35 kg/m2) following a conservative dietary program (diet) and patients undergoing RYGB surgery within a 6-month follow-up. Overall, changes in BMI were not associated with changes of both 5-HTT and NAT availability, while 5-HTT availability in the dorsal raphe nucleus (DRN) prior to intervention was associated with substantial BMI reduction after RYGB surgery and inversely related with modest BMI reduction after diet. Taken together, the data of our study indicate that 5-HTT and NAT are involved in the pathomechanism of obesity and have the potential to serve as predictors of treatment outcomes.
RESUMEN
The transcriptional activator retinoic acid (RA) supports axonal regeneration of several neuronal cell populations in vitro, and it has been suggested that its receptor RARbeta2 may be used to support axonal regeneration in the adult mammalian spinal cord. We have previously shown that spinal cord injury induces activity of the RA synthesizing enzyme retinaldehyde dehydrogenase (RALDH)2 in NG2-positive cells. This report quantifies the increase of RALDH2 protein in the injured spinal cord and characterizes the RALDH2/NG2 expressing cells probably as a unique RA synthesizing subpopulation of activated oligodendrocyte precursors or "polydendrocytes". In the uninjured spinal cord low levels of RALDH2 are present in oligodendrocytes as well as in the meninges and in blood vessels. Following injury there is a significant increase in RALDH2 in these latter two tissues and, given that the RALDH2/NG2 positive cells are clustered in the same area, this implies that these are specific foci of RA synthesis. It is presumed that these cells release RA in a paracrine fashion in the region of the wound; however, the RALDH2/NG2-immunoreactive cells expressed the retinoid receptors RARalpha, RARbeta, RXRalpha and RXRbeta, suggesting that RA also serves an autocrine function.