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Evidence of hypothalamic degeneration in the anorectic anx/anx mouse
Author(s) -
Nilsson Ida A. K.,
Thams Sebastian,
Lindfors Charlotte,
Bergstrand Anita,
Cullheim Staffan,
Hökfelt Tomas,
Johansen Jeanette E.
Publication year - 2011
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.21075
Subject(s) - biology , endocrinology , medicine , hypothalamus , neuropeptide , microglia , arcuate nucleus , neuropeptide y receptor , in situ hybridization , median eminence , central nervous system , receptor , gene expression , inflammation , immunology , gene , biochemistry
Mice homozygous for the anorexia ( anx ) mutation are characterized by poor food intake and death by three to five weeks after birth. By P21 these mice display lower density of hypothalamic neuropeptides, including Agouti gene‐related protein (AGRP). The AGRP/neuropeptide Y (NPY) system of the anx/anx mice develops normally until postnatal day (P) 12, then the normal increase in fiber density ceases, in some areas even distinctly decreases. This overlaps with activation of microglia, indicating an inflammatory and/or degenerative process. Here we studied, by in situ hybridization and immunohistochemistry (IHC), the expression of major histocompatibility complex (MHC) class I‐related molecules and markers for cellular reactivity in hypothalamus of anx/anx mice. MHC class I transcript and ‐related proteins were found in arcuate nucleus (Arc), presumably both in neurons and glia, the latter also in areas innervated by AGRP (NPY) neurons. In the anx/anx hypothalamus, using TUNEL labeling, significantly higher number of apoptotic cells were found compared with +/+ mice, and active caspase 6 immunoreactivity was detected in degenerating NPY‐fibers as well as signs of “microglia‐associated cell death”. In addition, Y1 receptor‐labeled processes and soma of pro‐opiomelanocortin (POMC) neurons, were markedly decreased at P21. These results support the hypothesis of degeneration of hypothalamic arcuate neuron populations in the anx/anx mice, whereby the AGRP system may be first affected, the changes in the POMC system being secondary in this process. © 2010 Wiley‐Liss, Inc.