Hypothalamic Mitochondrial Dysfunction Associated with Anorexia in the Anx/Anx Mouse
Hypothalamic mitochondrial dysfunction associated with anorexia in the anx/anx mouse Charlotte Lindforsa,b,1, Ida A. K. Nilssona,b,c,1,2, Pablo M. Garcia-Rovesd,e, Aamir R. Zuberif, Mohsen Karimib,g, Leah Rae Donahuef, Derry C. Roopenianf, Jan Mulderh,i, Mathias Uhlénj, Tomas J. Ekströmb,g, Muriel T. Davissonf, Tomas G. M. Hökfeltc,i,2, Martin Schallinga,b, and Jeanette E. Johansena,b Departments of aMolecular Medicine and Surgery and gClinical Neuroscience, Karolinska Institutet, 171 76 Stockholm, Sweden; bCenter for Molecular Medicine, Karolinska University Hospital, 171 76 Stockholm, Sweden; Departments of cNeuroscience and dPhysiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden; eDiabetes and Obesity Laboratory, Institute for Biomedical Research August Pi i Sunyer and Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders, 08036 Barcelona, Spain; fThe Jackson Laboratory, Bar Harbor, ME 04609; hEuropean Neuroscience Institute at Aberdeen, University of Aberdeen, Aberdeen AB25 2ZD, United Kingdom; iScience for Life Laboratory, 171 21 Stockholm, Sweden; and jDepartment of Biotechnology, AlbaNova University Center, 106 91 Stockholm, Sweden Contributed by Tomas G. M. Hökfelt, September 16, 2011 (sent for review August 23, 2010) The anorectic anx/anx mouse exhibits disturbed feeding behavior fibers immunoreactive (ir) for AGRP and NPY (7, 8, 10, 11, 16), and aberrances, including neurodegeneration, in peptidergic neu- as well as α-melanocyte–stimulating hormone (αMSH) and anx/anx rons in the appetite regulating hypothalamic arcuate nucleus. Poor CART (7, 9). In the mouse, the orexigenic AGRP system feeding in infants, as well as neurodegeneration, are common develops normally until P12, after which the normal, continuous increase in AGRP-ir fiber density in the main projection areas phenotypes in human disorders caused by dysfunction of the ceases, and in some areas even decreases.
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