Abstract：
:Long-term use of anti-diabetic agents has become commonplace as rates of obesity, metabolic syndrome and diabetes continue to escalate. Metformin, a commonly used anti-diabetic drug, has been shown to have many beneficial effects outside of its therapeutic regulation of glucose metabolism and insulin sensitivity. Studies on metformin's effects on the central nervous system are limited and predominantly consist of in vitro studies and a few in vivo studies with short-term treatment in relatively young animals; some provide support for metformin as a neuroprotective agent while others show evidence that metformin may be deleterious to neuronal survival. In this study, we examined the effect of long-term metformin treatment on brain neurotrophins and cognition in aged male C57Bl/6 mice. Mice were fed control (C), high-fat (HF) or a high-fat diet supplemented with metformin (HFM) for 6 months. Metformin decreased body fat composition and attenuated declines in motor function induced by a HF diet. Performance in the Morris water maze test of hippocampal based memory function, showed that metformin prevented impairment of spatial reference memory associated with the HF diet. Quantitative RT-PCR on brain homogenates revealed decreased transcription of BDNF, NGF and NTF3; however protein levels were not altered. Metformin treatment also decreased expression of the antioxidant pathway regulator, Nrf2. The decrease in transcription of neurotrophic factors and Nrf2 with chronic metformin intake, cautions of the possibility that extended metformin use may alter brain biochemistry in a manner that creates a vulnerable brain environment and warrants further investigation.
journal_name
Behav Brain Resjournal_title
Behavioural brain researchauthors
Allard JS,Perez EJ,Fukui K,Carpenter P,Ingram DK,de Cabo Rdoi
10.1016/j.bbr.2015.12.012subject
Has Abstractpub_date
2016-03-15 00:00:00pages
1-9eissn
0166-4328issn
1872-7549pii
S0166-4328(15)30326-0journal_volume
301pub_type
杂志文章abstract：:When rats are placed in a novel environment, they alternate between progression and stopping: in the course of a session they stop briefly in many places, but in one or two places they also stop for very long periods. The place in which they stay for the longest cumulative time is defined as the rat's home base. In th...
journal_title：Behavioural brain research
pub_type： 杂志文章
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
pub_type： 杂志文章
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
pub_type： 杂志文章,评审
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
pub_type： 杂志文章
doi：10.1016/0166-4328(90)90105-n
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journal_title：Behavioural brain research
pub_type： 杂志文章
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更新日期：1994-10-20 00:00:00
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journal_title：Behavioural brain research
pub_type： 杂志文章
doi：10.1016/j.bbr.2009.07.001
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journal_title：Behavioural brain research
pub_type： 杂志文章
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更新日期：1997-09-01 00:00:00
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journal_title：Behavioural brain research
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doi：10.1016/j.bbr.2004.12.006
更新日期：2005-05-28 00:00:00
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
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doi：10.1016/j.bbr.2010.05.037
更新日期：2010-12-25 00:00:00
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journal_title：Behavioural brain research
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journal_title：Behavioural brain research
pub_type： 杂志文章
doi：10.1016/0166-4328(85)90165-2
更新日期：1985-10-01 00:00:00
abstract：:The lighting environment where the baby born prematurely is placed is different from that experienced in utero. As early exposure to light may affect the immature visual system we have attempted to quantify the neonatal ocular light dose. Lighting surveys performed in 7 neonatal units (NNUs) suggested that mean unit i...
journal_title：Behavioural brain research
pub_type： 杂志文章,评审
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更新日期：1992-07-31 00:00:00
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journal_title：Behavioural brain research
pub_type： 杂志文章
doi：10.1016/j.bbr.2008.08.030
更新日期：2009-02-11 00:00:00
