Memantine - neuroprotective drug in aging brain

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 neuron...

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Bibliographic Details
Published in:Polish journal of pathology 2013-10, Vol.64 (3), p.196-203
Main Authors: Karolczak, Dominika, Sawicka, Emilia, Dorszewska, Jolanta, Radel, Anna, Bodnar, Magdalena, Błaszczyk, Agata, Jagielska, Joanna, Marszałek, Andrzej
Format: Article
Language:English
Subjects:
Aging
Aging - metabolism
Animals
Antibodies
Apoptosis
Apoptosis - drug effects
Brain
Brain - drug effects
Brain - metabolism
Caspase 3 - biosynthesis
Caspase 9 - biosynthesis
Catheters
Disease
Drug dosages
Enzyme Activation - drug effects
Enzymes
Female
Immunohistochemistry
Memantine - pharmacology
Neuroprotective Agents - pharmacology
Rats
Rats, Wistar
Rodents
Variance analysis
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Summary: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.
ISSN:1233-9687
2084-9869
DOI:10.5114/PJP.2013.38139