Affiliations: [a] 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 | [b] Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), University of Lisbon, Lisbon, Portugal | [c] Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal
Correspondence:
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Correspondence to: Cristina W. Nogueira, Laboratório de Síntese, Reatividade e Avaliação Farmacológica e Toxicológica de Organocalcogênios, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Santa Maria, CEP 97105-900, RS, Brazil. Tel.: +55 55 3220 8140, Fax: +55 55 3220 8978; E-mail: [email protected] or Cecília M.P. Rodrigues, Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon 1649-003, Portugal. Tel.: +351 21 794 6490; Fax: +351 21 794 6491; E-mail: [email protected].
Abstract: 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.
