Abstract:
:The present study investigated the effects of a single intravenous (i.v.) dose of Vitamin C (ascorbate, ASC) on spatial memory in APP/PSEN1 mice, an Alzheimer's disease model. First, we confirmed the uptake time course in ASC-depleted gulo (-/-) mice, which cannot synthesize ASC. Differential tissue uptake was seen based on ASC transporter distribution. Liver (SVCT1 and SVCT2) ASC was elevated at 30, 60 and 120 min post-treatment (125 mg/kg, i.v.), whereas spleen (SVCT2) ASC increased at 60 and 120 min. There was no detectable change in cortical (SVCT2 at choroid plexus, and neurons) ASC within the 2-h interval, although the cortex preferentially retained ASC. APP/PSEN1 and wild type (WT) mice at three ages (3, 9, or 20 months) were treated with ASC (125 mg/kg, i.v.) or saline 45 min before testing on the Modified Y-maze, a two-trial task of spatial memory. Memory declined with age and ASC treatment improved performance in 9-month-old APP/PSEN1 and WT mice. APP/PSEN1 mice displayed no behavioral impairment relative to WT controls. Although dopamine and metabolite DOPAC decreased in the nucleus accumbens with age, and improved spatial memory was correlated with increased dopamine in saline treated mice, acute ASC treatment did not alter monoamine levels in the nucleus accumbens. These data show that the Modified Y-maze is sensitive to age-related deficits, but not additional memory deficits due to amyloid pathology in APP/PSEN1 mice. They also suggest improvements in short-term spatial memory were not due to changes in the neuropathological features of AD or monoamine signaling.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
Kennard JA,Harrison FEdoi
10.1016/j.bbr.2014.01.044subject
Has Abstractpub_date
2014-05-01 00:00:00pages
34-42eissn
0166-4328issn
1872-7549pii
S0166-4328(14)00058-8journal_volume
264pub_type
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