TY - JOUR
T1 - Effects of β-hydroxy-β-methyl butyrate on working memory and cognitive flexibility in an animal model of aging
AU - Hankosky, Emily R.
AU - Sherrill, Luke K.
AU - Ruvola, Lauren A.
AU - Haake, Rachel M.
AU - Kim, Taehyeon
AU - Hammerslag, Lindsey R.
AU - Kougias, Daniel G.
AU - Juraska, Janice M.
AU - Gulley, Joshua M.
N1 - Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/8/9
Y1 - 2017/8/9
N2 - Objectives: Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Methods: Beginning ∼12 months of age, male and female Long–Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Results: Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Discussion: Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.
AB - Objectives: Normal aging results in cognitive decline and nutritional interventions have been suggested as potential approaches for mitigating these deficits. Here, we used rats to investigate the effects of short- and long-term dietary supplementation with the leucine metabolite β-hydroxy-β-methyl butyrate (HMB) on working memory and cognitive flexibility. Methods: Beginning ∼12 months of age, male and female Long–Evans rats were given twice daily access to sipper tubes containing calcium HMB (450 mg/kg) or vehicle (285 mg/kg calcium lactate) in a sucrose solution (20% w/v). Supplementation continued for 1 or 7 months (middle- and old-age (OA) groups, respectively) before testing began. Working memory was assessed by requiring rats to respond on a previously sampled lever following various delays. Cognitive flexibility was assessed by training rats to earn food according to a visual strategy and then, once acquired, shifting to an egocentric response strategy. Results: Treatment with HMB improved working memory performance in middle-age (MA) males and OA rats of both sexes. In the cognitive flexibility task, there was a significant age-dependent deficit in acquisition of the visual strategy that was not apparent in OA males treated with HMB. Furthermore, HMB ameliorated an apparent deficit in visual strategy acquisition in MA females. Discussion: Together, these findings suggest that daily nutritional supplementation with HMB facilitates learning and improves working memory performance. As such, HMB supplementation may mitigate age-related cognitive deficits and may therefore be an effective tool to combat this undesirable feature of the aging process.
KW - Aging
KW - Cognitive flexibility
KW - Prefrontal cortex
KW - Working memory
KW - β-Hydroxy-β-methyl butyrate
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U2 - 10.1080/1028415X.2016.1145376
DO - 10.1080/1028415X.2016.1145376
M3 - Article
C2 - 26896292
AN - SCOPUS:84978539249
SN - 1028-415X
VL - 20
SP - 379
EP - 387
JO - Nutritional Neuroscience
JF - Nutritional Neuroscience
IS - 7
ER -