A multifunctional compound ebselen reverses memory impairment, apoptosis and oxidative stress in a mouse model of sporadic Alzheimer's disease

• Published in: Journal of psychiatric research Vol. 109; pp. 107 - 117
• Main Authors: Martini, Franciele, Rosa, Suzan Gonçalves, Klann, Isabella Pregardier, Fulco, Bruna Cruz Weber, Carvalho, Fabiano Barbosa, Rahmeier, Francine Luciano, Fernandes, Marilda Cruz, Nogueira, Cristina Wayne
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2019
• Subjects: Alzheimer Disease - drug therapy; Animals; Antioxidants - pharmacology; Apoptosis; Apoptosis - drug effects; Azoles - administration & dosage; Azoles - pharmacology; Disease Models, Animal; Ebselen; Male; Memory; Memory Disorders - drug therapy; Mice; Neuroprotective; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacology; Organoselenium; Organoselenium Compounds - administration & dosage; Organoselenium Compounds - pharmacology; Oxidative Stress - drug effects; Selenium; Selenium - pharmacology; Neuroprotective; Ebselen; Selenium; Organoselenium; Memory; Apoptosis
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2018.11.021

Alzheimer 's disease (AD) is characterized by progressive cognitive decline including memory impairment, cortical dysfunction, and neuropsychiatric disturbances. The drug discovery to treat AD consists to develop compounds able to act in multiple molecular targets involved in the pathogenesis of the disease and the repositioning of old drugs for new application. This way, the intracerebroventricular (icv) injection of streptozotocin (STZ) has been used as a metabolic model of sporadic AD. The aim of the present study was to investigate whether ebselen (1–10 mg/kg), a multifunctional selenoorganic compound, ameliorates memory impairment, hippocampal oxidative stress, apoptosis and cell proliferation in a mouse model of sporadic AD induced by icv STZ (3 mg/kg, 1 μl/min). The administration of ebselen (10 mg/kg, i.p.) reversed memory impairment and hippocampal oxidative stress, by increasing the activities of antioxidant enzymes and the level of a non-enzymatic antioxidant defense, in Swiss mice administered with icv STZ. The anti-apoptotic property of ebselen was demonstrated by its effectiveness against the increase in the ratios of Bax/Bcl-2, cleaved PARP/PARP and the cleaved caspase-3 levels in the hippocampus of icv STZ mice. Although ebselen reversed memory impairment, it was ineffective against the reduction in the number of BrdU positive cells induced by icv STZ. In conclusion, the multifunctional selenoorganic compound ebselen was effective to reverse memory impairment, hippocampal oxidative stress and apoptosis in a mouse model of sporadic AD induced by icv STZ. •Ebselen reverses memory impairment in a sporadic model of AD.•Ebselen reverses apoptosis in a sporadic model of AD.•Ebselen reverses oxidative stress in a sporadic model of AD.•Ebselen is a multifunctional compound.