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, 15 (1), e0226806

Effects of Supplemental Creatine and Guanidinoacetic Acid on Spatial Memory and the Brain of Weaned Yucatan Miniature Pigs


Effects of Supplemental Creatine and Guanidinoacetic Acid on Spatial Memory and the Brain of Weaned Yucatan Miniature Pigs

Jason L Robinson et al. PLoS One.


The emergence of creatine as a potential cognitive enhancement supplement for humans prompted an investigation as to whether supplemental creatine could enhance spatial memory in young swine. We assessed memory performance and brain concentrations of creatine and its precursor guanidinoacetic acid (GAA) in 14-16-week-old male Yucatan miniature pigs supplemented for 2 weeks with either 200 mg/kg∙d creatine (+Cr; n = 7) or equimolar GAA (157 mg/kg∙d) (+GAA; n = 8) compared to controls (n = 14). Spatial memory tests had pigs explore distinct sets of objects for 5 min. Objects were spatially controlled, and we assessed exploration times of previously viewed objects relative to novel objects in familiar or novel locations. There was no effect of either supplementation on memory performance, but pigs successfully identified novel objects after 10 (p < 0.01) and 20 min (p < 0.01) retention intervals. Moreover, pigs recognized spatial transfers after 65 min (p < 0.05). Regression analyses identified associations between the ability to identify novel objects in memory tests and concentrations of creatine and GAA in cerebellum, and GAA in prefrontal cortex (p < 0.05). The concentration of creatine in brain regions was not influenced by creatine supplementation, but GAA supplementation increased GAA concentration in cerebellum (p < 0.05), and the prefrontal cortex of +GAA pigs had more creatine/g and less GAA/g compared to +Cr pigs (p < 0.05). Creatine kinase activity and maximal reaction velocity were also higher with GAA supplementation in prefrontal cortex (p < 0.05). In conclusion, there appears to be a relationship between memory performance and guanidino compounds in the cerebellum and prefrontal cortex, but the effects were unrelated to dietary supplementation. The cerebellum is identified as a target site for GAA accretion.

Conflict of interest statement

The authors have declared that no competing interests exist.


Fig 1
Fig 1. Schematic of testing apparatus.
The testing apparatus was a 152 x 152 cm box with a latchable door. The rectangles within the box perimeter represent sites where objects could be attached for pig exploration. Fig 1a-c: 4-Object Test. The initial exposure is represented in (Fig 1a), the second exposure (Fig 1b) and the test exposure (Fig 1c). In (Fig 1c), subscript M denotes that this object has been moved from the previous exposure. Fig 1d: 24-Hour Recall Test. During one episode, pigs were tested to distinguish between novel object C and object A (Fig 1d). Object A1 was viewed 24-h prior during the 4-object test in Fig 1c. Fig 1e-f: Short-Term 2-Object Test. The initial exposure (Fig 1e) and the test exposure (Fig 1f). In (Fig 1f), the object D is novel.
Fig 2
Fig 2. Regressions between brain guanidino compounds and performance.
Regression analyses identified significant relationships between concentrations of GAA in the PFC and time exploring a familiar object during the 4-object test (Fig 2a), creatine in the cerebellum and time exploring a moved object during the 4-object test (Fig 2b) and GAA in the cerebellum and time exploring a novel object during the 24-hour recall test (Fig 2c).

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