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bioRxiv · 10.1101/537720

Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice

Bracke, A.·Domanska, G.·Bracke, K.·Harzsch, S.·van den Brandt, J.·Broeker, B.·von Bohlen und Halbach, O.
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Abstract

AbstractsO_ST_ABSBackgroundC_ST_ABSObesity has become a severe problem among the worlds population with clearly increasing prevalence over the last decades. Because obesity is associated with several comorbidities (e.g. hypertension or cancer) it constitutes an increasing burden for the health care system. Correlations between obesity and cognition have been studied in humans with ambivalent results. Here, we studied the effects of obesity on hippocampus dependent learning and memory and cell morphology in a mouse model of obesity. MethodsThe body mass of male and female Lep+/+(wt) and Lepob/ob(ob/ob) animals with access to food and water ad libitum was measured between postnatal day 60-200 and animals with clear adiposity (4-6 months) were further analyzed. Adult hippocampal neurogenesis in the dentate gyrus was examined using phosphohistone H3 as a marker for proliferation, doublecortin as a marker for differentiation and caspase3 as a marker for apoptosis. Moreover, the density of dendritic spines on apical and basal dendrites of pyramidal neurons of the cornu ammonis 1 (CA1) were analyzed using Golgi impregnation. In addition, mice were subjected to the open field and Morris water maze test in order to analyze locomotor activity and spatial learning. ResultsThe body weight of ob/ob mice nearly doubled during the first 120 postnatal days. Adult hippocampal neurogenesis was reduced in ob/ob mice due to reduced cell proliferation. Dendritic spine densities in the hippocampal area CA1 were not altered in ob/ob mice. Four to six months old ob/ob mice showed reduced locomotor activity in the open field test but similar performance in the Morris water maze compared to control mice. ConclusionOur data show that alterations in adult neurogenesis in leptin-deficient mice are not associated with an impairment in spatial learning abilities. Moreover, ob/ob mice are inconspicuous in the Morris water maze and do not display altered spine densities in the hippocampus, suggesting that obesity does not have a severe impact upon hippocampal neuronal plasticity and spatial learning.

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Bracke, A., Domanska, G., Bracke, K., Harzsch, S., van den Brandt, J., Broeker, B., von Bohlen und Halbach, O.. 2019-02-01. Obesity alters mobility and adult neurogenesis, but not hippocampal dependent learning in ob/ob mice. https://doi.org/10.1101/537720

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