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Excitatory neurosteroids attenuate apoptotic and excitotoxic cell death in primary cortical neurons

100%

Leskiewicz M., Jantas D., Budziszewska B., Lason W.

Journal of Physiology and Pharmacology

2008

tom 59

nr 3

457-475

Some neurosteroids show neuroprotective action in in vitro and in vivo studies, but their interaction with apoptotic/necrotic processes has been only partially unraveled. The aim of the present study was to examine the effect of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), pregnenolone (PGL) and allopregnanolone (Allo) on staurosporine-, glutamate-, and NMDA-induced damage in primary cortical neuronal culture. DHEA, DHEAS and PGL (0.1 and 1 µM) inhibited the staurosporine-evoked LDH release and decreased the number of apoptotic cells as shown by Hoechst`s staining, whereas Allo was without effect. The neurosteroids affected neither the staurosporine-evoked changes in caspase-3 activity nor the decrease in mitochondrial membrane potential. It was also shown that protective effects of DHEA, DHEAS and PGL against staurosporine-induced LDH release were attenuated by extracellular signal-regulated kinase (ERK) - mitogen-activated protein kinase (MAPK) inhibitor – PD 98059 (5 µM) but not by phosphatidylinositol-3-kinase (PI3-K) inhibitors such as LY 294002 (1 µM) or wortmannin (10 nM). The involvement of ERK2-MAPK in protective effects of neurosteroids was confirmed by Western blot study. Further study demonstrated that glutamate-induced cell damage was attenuated by DHEA, DHEAS, and PGL, but not by Allo. None of the steroids influenced NMDA-induced LDH release. The results of the present in vitro studies suggest that excitatory neurosteroids DHEA, DHEAS and PGL at physiological concentrations participate in the inhibition of cortical neuronal degeneration elicited by staurosporine and glutamate, whereas the most potent positive modulator of GABAA receptor - Allo - has no effect. Moreover, neurosteroids appear to attenuate the staurosporine-induced cell damage in a caspase-3 independent way and their neuroprotective mechanism of action involves the increase in ERK-MAPK phosphorylation.

Cytochrome P450 aromatase expression in canine nervous tissue: an immunohistochemical study

100%

Karahan S., Yarim M., Harada N.

Polish Journal of Veterinary Sciences

2008

tom 11

nr 4

347-352

The enzyme cytochrome P450 aromatase is responsible for conversion of androgens to estrogens. Estrogens have been implicated in neurophysiology and neuropathology. The present study investigated the presence of aromatase immunoreactivity in the temporal, parietal and occipital cortices, olfactory bulb, cerebellum, and choroid plexus of the normal dog. Aromatase immunoreactivity was localized exclusively in neurons in the cortices and olfactory bulb. Immunoreactivity was also present in a small number of astrocytes in the substantia alba of the cerebellum. In the cortical regions, immunoreactive neurons, morphologically identified as pyramidal cells, were found throughout Layer II down to Layer VI, but not all pyramidal neurons were immunoreactive. In the olfactory bulb, immunoreactive neurons were mainly observed in mitral cells and inner granular cell layers. In the cerebellum, immunoreactivity was present in neurons of the deep cerebellar nuclei and in some neurons of the molecular and granular cell layers. Immunoreactivity was also present in endothelial cells of the subarachnoid vessels and those adjacent to ventricles in the cortex. The presence of well defined cytoplasmic aromatase immunoreactivity in neurons, some astrocytes, and endothelial cells suggests estrogen involvement in CNS physiology and function in the dog. The presence of aromatase in ependymal cells lining cerebral ventricles and choroid epithelial cells suggests that these cells may be partially responsible for estrogen concentration in the cerebrospinal fluid.

Ograniczanie wyników

1 Journal of Physiology and Pharmacology

1 Polish Journal of Veterinary Sciences

1 Budziszewska B.

1 Harada N.

1 Jantas D.

1 Karahan S.

1 Lason W.

1 Leskiewicz M.

1 Yarim M.

2 2008

Wyniki wyszukiwania

Excitatory neurosteroids attenuate apoptotic and excitotoxic cell death in primary cortical neurons

Cytochrome P450 aromatase expression in canine nervous tissue: an immunohistochemical study