| First Author | Pan Y | Year | 2018 |
| Journal | Brain Behav Immun | Volume | 70 |
| Pages | 36-47 | PubMed ID | 29545118 |
| Mgi Jnum | J:351924 | Mgi Id | MGI:7703869 |
| Doi | 10.1016/j.bbi.2018.03.007 | Citation | Pan Y, et al. (2018) Cognitive benefits of lithium chloride in APP/PS1 mice are associated with enhanced brain clearance of beta-amyloid. Brain Behav Immun 70:36-47 |
| abstractText | Epidemiological evidence suggests that people with bipolar disorder prescribed lithium exhibit a lower risk of Alzheimer's disease (AD) relative to those prescribed other mood-stabilizing medicines. Lithium chloride (LiCl) reduces brain beta-amyloid (Abeta) levels, and the brain clearance of Abeta is reduced in AD. Therefore, the purpose of this study was to assess whether the cognitive benefits of LiCl are associated with enhanced brain clearance of exogenously-administered Abeta. The brain clearance of intracerebroventricularly (icv) administered (125)I-Abeta(42) was assessed in male Swiss outbred mice administered daily oral NaCl or LiCl (300mg/kg for 21days). LiCl exhibited a 31% increase in the brain clearance of (125)I-Abeta(42) over 10min, which was associated with a 1.6-fold increase in brain microvascular expression of the blood-brain barrier efflux transporter low density lipoprotein receptor-related protein 1 (LRP1) and increased cerebrospinal fluid (CSF) bulk-flow. 8-month-old female wild type (WT) and APP/PS1 mice were also administered daily NaCl or LiCl for 21days, which was followed by cognitive assessment by novel object recognition and water maze, and measurement of soluble Abeta(42), plaque-associated Abeta(42), and brain efflux of (125)I-Abeta(42). LiCl treatment restored the long-term spatial memory deficit observed in APP/PS1 mice as assessed by the water maze (back to similar levels of escape latency as WT mice), but the short-term memory deficit remained unaffected by LiCl treatment. While LiCl did not affect plaque-associated Abeta(42), soluble Abeta(42) levels were reduced by 49.9% in APP/PS1 mice receiving LiCl. The brain clearance of (125)I-Abeta(42) decreased by 27.8% in APP/PS1 mice, relative to WT mice, however, LiCl treatment restored brain (125)I-Abeta(42) clearance in APP/PS1 mice to a rate similar to that observed in WT mice. These findings suggest that the cognitive benefits and brain Abeta(42) lowering effects of LiCl are associated with enhanced brain clearance of Abeta(42), possibly via brain microvascular LRP1 upregulation and increased CSF bulk-flow, identifying a novel mechanism of protection by LiCl for the treatment of AD. |
