Spermidine/spermine N1-acetyltransferase overexpression in mice induces hypoactivity and spatial learning impairment

Kaasinen, S.K.; Oksman, M.; Alhonen, L.; Tanila, H.; Jänne, J.

Pharmacology Biochemistry and Behavior 78(1): 35-45


ISSN/ISBN: 0091-3057
PMID: 15159132
DOI: 10.1016/j.pbb.2004.02.001
Accession: 012576444

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The present work addresses the role of polyamines in learning and general behavior by subjecting transgenic mice overexpressing polyamine catabolic enzyme, spermidine/spermine N(1)-acetyltransferase (SSAT) and their syngenic littermates to neurobehavioral profiling assessment (SHIRPA) and to radial eight-arm maze. The general health and physiological conditions as well as the entire behavioral battery comprising of 34 parameters were recorded. The eight-arm radial maze (8-RAM) task included an initial acquisition task for 9 days followed by a 2-day retention test after a 2-week break. In addition, blood samples were taken for hormone analysis. Transgenic mice, which showed reduced motor activity, aggression and muscle tone, spent more time in the radial maze during initial acquisition and retention tasks as compared with syngenic mice. Moreover, the learning performance of transgenic females was significantly inferior to syngenic females. Interestingly, the levels of several hormones were significantly altered in SSAT transgenic mice; circulating adrenocorticotropic hormone (ACTH) and corticosterone levels were markedly increased while testosterone and thyroidal hormone levels were decreased. These changes may be related to the dramatic increase in brain putrescine levels in SSAT-overexpressing (SSAT-OE) mice, but it is likewise possible that the behavioral changes and learning impairment are attributable to more peripheral mechanisms (such as alterations in steroid hormone metabolism), which in turn, could be a consequence of the disturbed polyamine homeostasis.