TY  - JOUR
AB  - Mitochondrial Membrane Protein-Associated Neurodegeneration is a rare 
      monogenic form of neurodegeneration characterized by iron accumulation 
      in the brain. It is due to variants in the orphan gene C19orf12.
       Since its definition in 2011, many scientific groups have investigated 
      the clinical features and molecular underpinnings of the disorder. In 
      this review, we summarize the main points of progress in this field, 
      trying to highlight the issues that need further attention and efforts 
      to speed up the diagnostic path, improve the existing treatment options,
       and define targeted therapies.
AU  - Gnutti, B.*
AU  - Iuso, A.
AU  - Angelini, C.*
AU  - Finazzi, D.*
C1  - 75231
C2  - 57857
CY  - Mdpi Ag, Grosspeteranlage 5, Ch-4052 Basel, Switzerland
TI  - An update and perspectives on mitochondrial membrane protein-associated neurodegeneration and C19orf12 research.
JO  - Brain Sci.
VL  - 15
IS  - 8
PB  - Mdpi
PY  - 2025
SN  - 2076-3425
ER  - 

TY  - JOUR
AB  - 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.
AU  - Griebsch, N.I.*
AU  - Kern, J.*
AU  - Hansen, J.*
AU  - Rullmann, M.*
AU  - Luthardt, J.*
AU  - Helfmeyer, S.*
AU  - Dekorsy, F.J.*
AU  - Soeder, M.*
AU  - Hankir, M.K.*
AU  - Zientek, F.*
AU  - Becker, G.A.*
AU  - Patt, M.*
AU  - Meyer, P.M.*
AU  - Dietrich, A.*
AU  - Blüher, M.
AU  - Ding, Y.S.*
AU  - Hilbert, A.*
AU  - Sabri, O.*
AU  - Hesse, S.*
C1  - 66679
C2  - 53268
TI  - Central serotonin/noradrenaline transporter availability and treatment success in patients with obesity.
JO  - Brain Sci.
VL  - 12
IS  - 11
PY  - 2022
SN  - 2076-3425
ER  - 

TY  - JOUR
AB  - Purpose: Obesity is thought to arise, in part, from deficits in the inhibitory control over appetitive behavior. Such motivational processes are regulated by neuromodulators, specifically acetylcholine (ACh), via α4β2* nicotinic ACh receptors (nAChR). These nAChR are highly enriched in the thalamus and contribute to the thalamic gating of cortico-striatal signaling, but also act on the mesoaccumbal reward system. The changes in α4β2* nAChR availability, however, have not been demonstrated in human obesity thus far. The aim of our study was, thus, to investigate whether there is altered brain α4β2* nAChR availability in individuals with obesity compared to normal-weight healthy controls. Methods: We studied 15 non-smoking individuals with obesity (body mass index, BMI: 37.8 ± 3.1 kg/m2; age: 39 ± 14 years, 9 females) and 16 normal-weight controls (non-smokers, BMI: 21.9 ± 1.7 kg/m2; age: 28 ± 7 years, 13 females) by using PET and the α4β2* nAChR selective (−)-[18F]flubatine, which was applied within a bolus-infusion protocol (294 ± 16 MBq). Volume-of-interest (VOI) analysis was performed in order to calculate the regional total distribution volume (VT). Results: No overall significant difference in VT between the individuals with obesity and the normal-weight volunteers was found, while the VT in the nucleus basalis of Meynert tended to be lower in the individuals with obesity (10.1 ± 2.1 versus 11.9 ± 2.2; p = 0.10), and the VT in the thalamus showed a tendency towards higher values in the individuals with obesity (26.5 ± 2.5 versus 25.9 ± 4.2; p = 0.09). Conclusion: While these first data do not show greater brain α4β2* nAChR availability in human obesity overall, the findings of potentially aberrant α4β2* nAChR availability in the key brain regions that regulate feeding behavior merit further exploration.
AU  - Schweickert de Palma, E.*
AU  - Günnewig, T.*
AU  - Rullmann, M.*
AU  - Luthardt, J.*
AU  - Hankir, M.K.*
AU  - Meyer, P.M.*
AU  - Becker, G.A.*
AU  - Patt, M.*
AU  - Martin, S.*
AU  - Hilbert, A.*
AU  - Blüher, M.
AU  - Sabri, O.*
AU  - Hesse, S.*
C1  - 67098
C2  - 53470
CY  - St Alban-anlage 66, Ch-4052 Basel, Switzerland
TI  - Availability of central α4β2* nicotinic acetylcholine receptors in human obesity.
JO  - Brain Sci.
VL  - 12
IS  - 12
PB  - Mdpi
PY  - 2022
SN  - 2076-3425
ER  -