p,p'-Methoxyl-diphenyl diselenide prevents neurodegeneration and glial cell activation induced by streptozotocin in rats.
The purpose of this study was to investigate possible molecular targets involved in the neuroprotective effect of p,p'-methoxyl-diphenyl diselenide [(MeOPhSe)2], using a streptozotocin (STZ)-induced sporadic dementia of Alzheimer's type rat model. Male Wistar rats were injected with STZ (1.0 mg/8 μl; 4 μl/ventricle). After 21 days of STZ injection, regular diet-fed rats were supplemented with 10 ppm of (MeOPhSe)2 during 30 days. At the end of this period, rats performed object recognition and step-down passive avoidance tasks. Apoptosis was assessed by TUNEL staining and active caspase-3. Glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, and microtubule associated protein 2 were determined by immunofluorescence in rat hippocampus. The results demonstrate that the (MeOPhSe)2 dietary supplementation reversed STZ-induced memory impairment by enhancing memory in sham rats. (MeOPhSe)2 was also effective in reducing STZ-induced apoptosis and preserving dendrites and synapses. Moreover, (MeOPhSe)2 inhibited activation of microglia and astrogliosis induced by STZ in the rat hippocampus. We conclude that the (MeOPhSe)2 neuroprotective action is related to inhibition of apoptosis and suppression of inflammation.
Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, Brazil.
Simone
S
Pinton
Tuane Bazanella
TB
Sampaio
Rita M
RM
Ramalho
Cecília M P
CM
Rodrigues
Cristina Wayne
CW
Nogueira
D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016566:Organoselenium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000633:toxicity*
D001555:Benzene Derivatives; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; C528548:p-methoxy-diphenyl diselenide; D013311:Streptozocin