2024-03-29T14:25:22Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/770872016-02-17T17:56:56Zcom_10261_22com_10261_1col_10261_275
Imaging hypothalamic activity using diffusion weighted magnetic resonance imaging in the mouse and human brain
Lizarbe, Blanca
Benítez, Ania
Sánchez-Montañés, Manuel
Lago-Fernández, L.
García-Martín, María L.
López-Larrubia, Pilar
Cerdán, Sebastián
Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
Ministerio de Ciencia y Tecnología (España)
Ministerio de Asuntos Exteriores y Cooperación (España)
Universidad Autónoma de Madrid
Hypothalamic appetite regulation is a vital homeostatic process underlying global energy balance in animals and humans, its disturbances resulting in feeding disorders with high morbidity and mortality. The objective evaluation of appetite remains difficult, very often restricted to indirect measurements of food intake and body weight. We report here, the direct, non-invasive visualization of hypothalamic activation by fasting using diffusion weighted magnetic resonance imaging, in the mouse brain as well as in a preliminary study in the human brain. The brain of fed or fasted mice or humans were imaged at 7 or 1.5Tesla, respectively, by diffusion weighted magnetic resonance imaging using a complete range of b values (10<b<2000s.mm -2). The diffusion weighted image data sets were registered and analyzed pixel by pixel using a biexponential model of diffusion, or a model-free Linear Discriminant Analysis approach. Biexponential fittings revealed statistically significant increases in the slow diffusion parameters of the model, consistent with a neurocellular swelling response in the fasted hypothalamus. Increased resolution approaches allowed the detection of increases in the diffusion parameters within the Arcuate Nucleus, Ventromedial Nucleus and Dorsomedial Nucleus. Independently, Linear Discriminant Analysis was able to classify successfully the diffusion data sets from mice and humans between fed and fasted states. Present results are consistent with increased glutamatergic neurotransmission during orexigenic firing, a process resulting in increased ionic accumulation and concomitant osmotic neurocellular swelling. This swelling response is spatially extendable through surrounding astrocytic networks until it becomes MRI detectable. Present findings open new avenues for the direct, non-invasive, evaluation of appetite disorders and other hypothalamic pathologies helping potentially in the development of the corresponding therapies. © 2012 Elsevier Inc.
This work was supported in part by grants SAF-2008-01327 and SAF2011-23622 to SC, grant CTQ-2010-20960-C02-02 to PLL, grants S-BIO-2006-0170 and S2010/BMD-2349 to SC, PLL andMSM and grant CAM/UAM (CCG10-UAM/TIC-5864) to LFLF. BL and ABSDC held predoctoral fellowships from the Spanish Ministry of Science and Technology (BES 2009-027615) and the Spanish Agency for International Cooperation and Development.
Peer Reviewed
2013-05-29T11:33:33Z
2013-05-29T11:33:33Z
2013
2013-05-29T11:33:34Z
artículo
http://purl.org/coar/resource_type/c_6501
issn: 1053-8119
e-issn: 1095-9572
NeuroImage 64: 448-457 (2013)
http://hdl.handle.net/10261/77087
10.1016/j.neuroimage.2012.09.033
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100006280
http://dx.doi.org/10.13039/501100003767
http://dx.doi.org/10.13039/501100004593
http://dx.doi.org/10.13039/100012818
en
#PLACEHOLDER_PARENT_METADATA_VALUE#
S2010/BMD-2349/I2M2
Preprint
http://dx.doi.org/10.1016/j.neuroimage.2012.09.033
Sí
open
Elsevier