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The effects of hyperammonemia in learning and brain metabolic activity

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Abstract

Ammonia is thought to be central in the development of hepatic encephalopathy. However, the specific relation of ammonia with brain energy depletions and learning has not been studied. Our work attempts to reproduce an increase in rat cerebral ammonia level, study the hyperamonemic animals’ performance of two learning tasks, an allocentric (ALLO) and a cue guided (CG) task, and elucidate the contribution of hyperammonemia to the differential energy requirements of the brain limbic system regions involved in these tasks. To assess these goals, four groups of animals were used: a control (CHA) CG group (n = 10), a CHA ALLO group (n = 9), a hyperammonemia (HA) CG group (n = 7), and HA ALLO group (n = 8). Oxidative metabolism of the target brain regions were assessed by histochemical labelling of cytochrome oxidase (C.O.). The behavioural results revealed that the hyperammonemic rats were not able to reach the behavioural criterion in either of the two tasks, in contrast to the CHA groups. The metabolic brain consumption revealed increased C.O. activity in the anterodorsal thalamus when comparing the HA ALLO group with the CHA ALLO group. Significant differences between animals trained in the CG task were observed in the prelimbic, infralimbic, parietal, entorhinal and perirhinal cortices, the anterolateral and anteromedial striatum, and the basolateral and central amygdala. Our findings may provide fresh insights to reveal how the differential damage to the brain limbic structures involved in these tasks differs according to the degree of task difficulty.

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Acknowledgments

This research was supported by Grants MICINN PSI2010-19348 and MEC AP2009-1714 to NA.

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Authors and Affiliations

  1. Laboratory of Neuroscience, Departamento de Psicología, Universidad de Oviedo, Plaza Feijoo s/n 33003, Oviedo, Spain

    Natalia Arias, Camino Fidalgo & Jorge L. Arias

  2. INEUROPA, Instituto de Neurociencias del Principado de Asturias, Oviedo, Spain

    Natalia Arias & Jorge L. Arias

  3. Laboratory of Neurobiology, Centro Investigación Príncipe Felipe, Valencia, Spain

    Vicente Felipo

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  1. Natalia Arias
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  2. Camino Fidalgo
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  3. Vicente Felipo
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  4. Jorge L. Arias
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Correspondence to Natalia Arias.

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Arias, N., Fidalgo, C., Felipo, V. et al. The effects of hyperammonemia in learning and brain metabolic activity. Metab Brain Dis 29, 113–120 (2014). https://doi.org/10.1007/s11011-013-9477-0

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