title: Memantine - neuroprotective drug in aging brain.
abstract: Aging is the process of progressive accumulation of changes over time, which is additionally connected with increasing susceptibility to some diseases and ultimately leads to death. Aging is associated mainly with loss of permanent cells, e.g. in heart, skeletal muscle and brain. During aging neurons die mainly in the apoptotic way. Apoptosis can be divided into three phases: initiation, execution and degradation. During the execution phase activation of specific enzymes, caspases, is observed. These enzymes are responsible for initiation of the death machinery. Caspase-9 is connected with the internal pathway of apoptosis, which begins at the mitochondrium in response to apoptotic stimulants, such as free radicals, UV radiation or chemotherapeutics. Before the executive phase starts, cytochrome c leaks from the mitochondrium to the cytoplasm, where it joins to the protein Apaf-1 and procaspase-9 and forms a complex called the apoptosome. Then procaspase-9 is converted by autolysis to caspase-9, which subsequently activates procaspase-3 to the active form which ultimately leads to apoptosis. Immunohistochemical analysis demonstrated a small decrease in caspase-9 and caspase-3 activation during normal aging and an increase in this process after application of stress factors. Also increased apoptosis in the cerebrum after administration of a drug for Alzheimer disease, memantine, to aging rats was observed. Taken together, the results obtained in this study seem to confirm the neuroprotective effect of memantine on increasing levels of cells with active caspase-3 and active caspase-9. It probably improves caspase-dependent apoptosis in the aging brain.
authors.affiliation: Andrzej Marszałek, MD, PhD, Collegium Medicum Nicolaus Copernicus University, Department of Clinical Pathomorphology, M. Skłodowskiej-Curie 9, 85-094 Bydgoszcz, tel. +48 52 5854200, fax +48 52 5854049, e-mail: amars@cm.umk.pl.
authors.forename: Dominika
authors.initials: D
authors.lastname: Karolczak
authors.forename: Emilia
authors.initials: E
authors.lastname: Sawicka
authors.forename: Jolanta
authors.initials: J
authors.lastname: Dorszewska
authors.forename: Anna
authors.initials: A
authors.lastname: Radel
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bodnar
authors.forename: Agata
authors.initials: A
authors.lastname: Błaszczyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Jagielska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Marszałek
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008559:Memantine / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D008559:Memantine