Hippocampal CysLT1R overexpression or activation accelerates memory deficits, synaptic dysfunction, and amyloidogenesis in young APP/PS1 transgenic mice.

Background: Our previous studies demonstrated that cysteinyl leukotrienes receptor 1 (CysLTR) knockout, pharmacological blockade, or hippocampus knockdown produced beneficial effects against Alzheimer's disease (AD); however, whether CysLTR upregulation has deleterious effects on AD remains elusive.

Methods: In this study, we investigated the changes in behaviors, hippocampal amyloidogenesis, and synapse plasticity after CysLTR overexpression by microinfusion of the lentiviral vector, containing its coding sequence of mouse (LV-CysLTR), into the bilateral dentate gyri (DG) of the hippocampus or CysLTR activation by repeated systemic administration of its agonist YM-17690 (0.1 mg/kg, once a day, i.

Simvastatin ameliorates memory impairment and neurotoxicity in streptozotocin-induced diabetic mice.

Diabetes comes with an additional burden of moderate to severe hyperlipidemia, but little is known about the effects of lipid-lowering therapy on diabetic complications such as diabetes-associated cognitive decline. Herein we investigated the effects of statins on memory impairment and neurotoxicity in streptozotocin-induced diabetic mice. Our data indicated that oral administration of simvastatin at 10 or 20mg/kg for 4weeks significantly ameliorated diabetes-associated memory impairment reflected by performance better in the Morris water maze and Y-maze tests.

Hippocampal CysLTR knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice.

Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLTR) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLTR in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLTR knockdown and CysLTR blockade on LPS-induced depressive-like behavior in mice.