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Evidence of hypothalamic degeneration in the anorectic anx/anx mouse.
- Source :
-
Glia [Glia] 2011 Jan; Vol. 59 (1), pp. 45-57. Date of Electronic Publication: 2010 Oct 21. - Publication Year :
- 2011
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Abstract
- 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.<br /> (Copyright © 2010 Wiley-Liss, Inc.)
- Subjects :
- Animals
Anorexia genetics
Apoptosis
Hypothalamus pathology
Immunohistochemistry
In Situ Hybridization
In Situ Nick-End Labeling
Mice
Mutation
Neurons metabolism
Neuropeptide Y genetics
Neuropeptide Y metabolism
Pro-Opiomelanocortin genetics
Pro-Opiomelanocortin metabolism
Anorexia metabolism
Hypothalamus metabolism
Major Histocompatibility Complex physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-1136
- Volume :
- 59
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Glia
- Publication Type :
- Academic Journal
- Accession number :
- 20967882
- Full Text :
- https://doi.org/10.1002/glia.21075