Analysis of the network of feeding neuroregulators using the Allen Brain Atlas

Abstract

The Allen Brain Atlas, the most comprehensive in situ hybridization database, covers over 21000 genes expressed in the mouse brain. Here we discuss the feasibility to utilize the ABA in research pertaining to the central regulation of feeding and we define advantages and vulnerabilities associated with the use of the atlas as a guidance tool. We searched for 57 feeding-related genes in the ABA, and of those 42 display distribution consistent with that described in previous reports. Detailed analyses of these 42 genes in the nucleus accumbens, ventral tegmental area, nucleus of the solitary tract, lateral hypothalamus, arcuate, paraventricular, ventromedial and dorsomedial nuclei suggests that molecules involved in feeding stimulation and termination are coexpressed in multiple consumption-related sites. Gene systems linked to energy needs, reward or satiation display a remarkably high level of overlap. This conclusion calls into question the classical concept of brain sites viewed as independent hunger or reward "centers" and favors the theory of a widespread feeding network comprising multiple neuroregulators affecting numerous aspects of consumption. KeywordsCNS; food intake; obesity; anorexia; neuropeptides The Allen Brain Atlas: Brief OverviewThe human brain is undoubtedly the organ of the body that we have the least knowledge about in relationship to its complexity. It has been estimated that 99% of the neuroscience literature focuses on only 1% of the genes expressed in the brain (Gewin, 2005). Deciphering spatial gene expression patterns in the central nervous system is crucial for our understanding of functional neuronal networks. It has been speculated that "in the brain, more than any other organ, function follows form" (Gewin, 2005).Correspondence and reprint requests should be addressed to: Pawel K. Olszewski, Ph.D. Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24 Uppsala, Sweden. Tel ++46184714362 Fax ++4618511540 E-mail: pawel.olszewski@neuro.uu.se. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Gong et al., 2003)]. Moreover, it also contains expression patterns from transgenic mouse lines that express green fluorescent protein (EGFP) reporter gene in cells that normally express a gene of interest. The GENSAT provides comprehensive information about the limited number of the mapped genes. Another project is the GenePaint atlas (www.genepaint.org), which displays in situ hybridization data of several thousand genes in selected sections of whole mouse embryos at embryonic day (E) 14.5 and as well as some genes in E10.5 embryos, E1...

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