Comparing the effect of the novel ionic cocrystal of lithium salicylate proline (LISPRO) with lithium carbonate and lithium salicylate on memory and behavior in female APPswe/PS1dE9 Alzheimer's mice. Issue 9 (17th May 2019)

• Record Type: Journal Article
• Authors: Habib, Ahsan; Shytle, R. Douglas; Sawmiller, Darrell; Koilraj, Selina; Munna, Sadia Afrin; Rongo, David; Hou, Huayan; Borlongan, Cesario V.; Currier, Glenn; Tan, Jun
• Is Part Of: Journal of neuroscience research. Volume 97:Issue 9(2019)
• Page Start: 1066
• Page End: 1080
• Publication Date: 2019-05-17
• Subjects: Alzheimer's disease -- cognitive impairment -- depression -- irritability -- transgenic mice; Neurobiology -- Periodicals; 612
• DOI: 10.1002/jnr.24438
• Languages: English
• ISSNs: 0360-4012

Abstract

Abstract: Alzheimer's disease (AD) is characterized by progressive decline of cognition and associated neuropsychiatric signs including weight loss, anxiety, depression, agitation, and aggression, which is particularly pronounced in the female gender. Previously, we have shown that a novel ionic co‐crystal of lithium salicylate proline (LISPRO) is an improved lithium formulation compared to the carbonate or salicylate form of lithium in terms of safety and efficacy in reducing AD pathology in Alzheimer's mice. The current study is designed to compare the prophylactic effects of LISPRO, lithium carbonate (LC), and lithium salicylate (LS) on cognitive and noncognitive impairments in female transgenic APPswe/PS1dE9 AD mice. Female APPswe/PS1dE9 mice at 4 months of age were orally treated with low‐dose LISPRO, LS, or LC for 9 months at 2.25 mmol lithium/kg/day followed by determination of body weight, growth of internal organs, and cognitive and noncognitive behavior. No significant differences in body or internal organ weight, anxiety or locomotor activity were found between lithium treated and untreated APPswe/PS1dE9 cohorts. LISPRO, LC, and LS prevented spatial cognitive decline, as determined by Morris water maze and depression as determined by tail suspension test. In addition, LISPRO treatment was superior in preventing associative memory decline determined by contextual fear conditioning and reducing irritability determined by touch escape test in comparison with LC and LS. In conclusion, low‐dose LISPRO, LC, and LS treatment prevent spatial cognitive decline and depression‐like behavior, while LISPRO prevented hippocampal‐dependent associative memory decline and irritability in APPswe/PS1dE9 mice. Abstract : We compared the prophylactic effects of LISPRO (LP), lithium carbonate (LC), and lithium salicylate (LS) treatment on cognitive and non‐cognitive impairments in female Alzheimer's disease transgenic mice. Low‐dose LP, LC, and LS treatment prevented spatial cognitive decline and depression‐like behavior, while LP alone prevented hippocampal dependent associative‐memory decline and irritability.