TY - JOUR
T1 - Chronic pyruvate supplementation increases exploratory activity and brain energy reserves in young and middle-aged mice
AU - Koivisto, Hennariikka
AU - Leinonen, Henri
AU - Puurula, Mari
AU - Hafez, Hani Sayed
AU - Barrera, Glenda Alquicer
AU - Stridh, Malin H
AU - Waagepetersen, Helle S.
AU - Tiainen, Mika
AU - Soininen, Pasi
AU - Zilberter, Yuri
AU - Tanila, Heikki
PY - 2016
Y1 - 2016
N2 - Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer's disease (AD) and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~800 mg/kg/day Na-pyruvate in their chow for 2-6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force, and endurance, and found no effects. Metabolic postmortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment, but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement.
AB - Numerous studies have reported neuroprotective effects of pyruvate when given in systemic injections. Impaired glucose uptake and metabolism are found in Alzheimer's disease (AD) and in AD mouse models. We tested whether dietary pyruvate supplementation is able to provide added energy supply to brain and thereby attenuate aging- or AD-related cognitive impairment. Mice received ~800 mg/kg/day Na-pyruvate in their chow for 2-6 months. In middle-aged wild-type mice and in 6.5-month-old APP/PS1 mice, pyruvate facilitated spatial learning and increased exploration of a novel odor. However, in passive avoidance task for fear memory, the treatment group was clearly impaired. Independent of age, long-term pyruvate increased explorative behavior, which likely explains the paradoxical impairment in passive avoidance. We also assessed pyruvate effects on body weight, muscle force, and endurance, and found no effects. Metabolic postmortem assays revealed increased energy compounds in nuclear magnetic resonance spectroscopy as well as increased brain glycogen storages in the pyruvate group. Pyruvate supplementation may counteract aging-related behavioral impairment, but its beneficial effect seems related to increased explorative activity rather than direct memory enhancement.
KW - Aging
KW - Alzheimer's disease
KW - Explorative activity
KW - Glycogen
KW - Memory
U2 - 10.3389/fnagi.2016.00041
DO - 10.3389/fnagi.2016.00041
M3 - Journal article
C2 - 27014054
AN - SCOPUS:84964570092
SN - 1663-4365
VL - 8
SP - 1
EP - 14
JO - Frontiers in Aging Neuroscience
JF - Frontiers in Aging Neuroscience
M1 - 41
ER -