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@ARTICLE{Bayer:162632,
      author       = {Bayer, David and Antonucci, Stefano and Müller, Hans-Peter
                      and Saad, Rami and Dupuis, Luc and Rasche, Volker and
                      Böckers, Tobias and Ludolph, Albert and Kassubek, Jan and
                      Roselli, Francesco},
      title        = {{D}isruption of orbitofrontal-hypothalamic projections in a
                      murine {ALS} model and in human patients.},
      journal      = {Translational neurodegeneration},
      volume       = {10},
      number       = {1},
      issn         = {2047-9158},
      address      = {London},
      publisher    = {Biomed Central},
      reportid     = {DZNE-2021-01328},
      pages        = {17},
      year         = {2021},
      note         = {CC BY},
      abstract     = {Increased catabolism has recently been recognized as a
                      clinical manifestation of amyotrophic lateral sclerosis
                      (ALS). The hypothalamic systems have been shown to be
                      involved in the metabolic dysfunction in ALS, but the exact
                      extent of hypothalamic circuit alterations in ALS is yet to
                      be determined. Here we explored the integrity of large-scale
                      cortico-hypothalamic circuits involved in energy homeostasis
                      in murine models and in ALS patients.The rAAV2-based
                      large-scale projection mapping and image analysis pipeline
                      based on Wholebrain and Ilastik software suites were used to
                      identify and quantify projections from the forebrain to the
                      lateral hypothalamus in the SOD1(G93A) ALS mouse model
                      (hypermetabolic) and the FusΔNLS ALS mouse model
                      (normo-metabolic). 3 T diffusion tensor imaging
                      (DTI)-magnetic resonance imaging (MRI) was performed on 83
                      ALS and 65 control cases to investigate cortical projections
                      to the lateral hypothalamus (LHA) in ALS.Symptomatic
                      SOD1(G93A) mice displayed an expansion of projections from
                      agranular insula, ventrolateral orbitofrontal and secondary
                      motor cortex to the LHA. These findings were reproduced in
                      an independent cohort by using a different analytic
                      approach. In contrast, in the FusΔNLS ALS mouse model
                      hypothalamic inputs from insula and orbitofrontal cortex
                      were maintained while the projections from motor cortex were
                      lost. The DTI-MRI data confirmed the disruption of the
                      orbitofrontal-hypothalamic tract in ALS patients.This study
                      provides converging murine and human data demonstrating the
                      selective structural disruption of hypothalamic inputs in
                      ALS as a promising factor contributing to the origin of the
                      hypermetabolic phenotype.},
      keywords     = {Amyotrophic Lateral Sclerosis: diagnostic imaging /
                      Amyotrophic Lateral Sclerosis: pathology / Animals / Brain
                      Mapping / Case-Control Studies / Cohort Studies / Diffusion
                      Tensor Imaging / Energy Metabolism / Humans / Hypothalamus:
                      diagnostic imaging / Hypothalamus: pathology /
                      Immunohistochemistry / Mice / Motor Cortex: growth $\&$
                      development / Motor Cortex: pathology / Neural Pathways:
                      diagnostic imaging / Neural Pathways: pathology / Prefrontal
                      Cortex: diagnostic imaging / Prefrontal Cortex: pathology /
                      RNA-Binding Protein FUS: genetics / Superoxide Dismutase-1:
                      genetics / Agranular insula (Other) / Amyotrophic lateral
                      sclerosis (Other) / Hypermetabolism (Other) / Lateral
                      hypothalamus (Other) / Orbitofrontal cortex (Other) / rAAV2
                      (Other)},
      cin          = {AG Roselli / AG Böckers / Clinical Study Center Ulm},
      ddc          = {570},
      cid          = {I:(DE-2719)1910001 / I:(DE-2719)1910002 /
                      I:(DE-2719)5000077},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34059131},
      pmc          = {pmc:PMC8168014},
      doi          = {10.1186/s40035-021-00241-6},
      url          = {https://pub.dzne.de/record/162632},
}