Abstract：
:The risk of Alzheimer's disease (AD) is higher in patients with type 2 diabetes mellitus (T2DM). Previous studies in high-fat diet-induced AD animal models have shown that brain insulin resistance in these animals leads to the accumulation of amyloid beta (Aβ) and the reduction in GSK-3β phosphorylation, which promotes tau phosphorylation to cause AD. No therapeutic treatments that target AD in T2DM patients have yet been discovered. Agmatine, a primary amine derived from l-arginine, has exhibited anti-diabetic effects in diabetic animals. The aim of this study was to investigate the ability of agmatine to treat AD induced by brain insulin resistance. ICR mice were fed a 60% high-fat diet for 12 weeks and received one injection of streptozotocin (100 mg/kg/ip) 4 weeks into the diet. After the 12-week diet, the mice were treated with agmatine (100 mg/kg/ip) for 2 weeks. Behaviour tests were conducted prior to sacrifice. Brain expression levels of the insulin signal molecules p-IRS-1, p-Akt, and p-GSK-3β and the accumulation of Aβ and p-tau were evaluated. Agmatine administration rescued the reduction in insulin signalling, which in turn reduced the accumulation of Aβ and p-tau in the brain. Furthermore, agmatine treatment also reduced cognitive decline. Agmatine attenuated the occurrence of AD in T2DM mice via the activation of the blunted insulin signal.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Kang S,Kim CH,Jung H,Kim E,Song HT,Lee JEdoi
10.1016/j.neuropharm.2016.10.029subject
Has Abstractpub_date
2017-02-01 00:00:00pages
467-479issue
Pt Aeissn
0028-3908issn
1873-7064pii
S0028-3908(16)30483-Xjournal_volume
113pub_type
杂志文章abstract：:Dieting induces depression and anxiety among other emotional symptoms. Animal models indicate that repeated access to palatable foods such as sugar induces depression and anxiety-like behavior when the food is no longer available. However, the neurobiological mechanisms of how dietary restriction influences mood have ...
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