Neuroprotective effect of ACTH (4-9) in degeneration of hippocampal nerve cells caused by dexamethasone: morphological, immunocytochemical and ultrastructural studies.
Sustained exposure to glucocorticosteroids (GCs), adrenal hormones secreted during stress, can cause neural degeneration. This is particularly so in the hippocampus, a principal neural target site for GCs. The purpose of this research was an assessment of the neuroprotective effect of ACTH (4-9) in degenerative changes of hippocampal neurons induced by synthetic GC-dexamethasone. Experiments were conducted on male Albino-Swiss mice. We studied the morphology of neurons in the dorsal hippocampus in slides stained with cresyl violet. Immunocytochemical analysis was carried out with the use of monoclonal antibody anti-MAP2 in order to detect alterations in the neuronal cytoskeleton. We also performed ultrastructural examinations of hippocampal neurons. Quantitative analysis of morphological changes was completed using a computer analyser of histological pictures. It was shown that dexamethasone administered in toxic doses evokes neuronal death in layer CA3 of the hippocampus. Results indicate that ACTH (4-9) shows protective effects in that model. Dexamethasone-induced damage to hippocampal pyramidal neurons (assessed by cell counts, immunocytochemical analysis of cytoskeletal alterations and ultrastructural studies) was significantly reduced in animals administered ACTH (4-9).
Sekita-Krzak
Joanna
J
Department of Histology and Embryology, Lab of Experimental Cytology of Medical University, 11 Radziwiłłowska St., 20-080 Lublin, Poland. jsekita@panaceum.am.lublin.pl.
Zebrowska-Lupina
Iwona
I
Czerny
Krystyna
K
Stepniewska
Maria
M
Wróbel
Andrzej
A
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors; D009410:Nerve Degeneration / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D010446:Peptide Fragments / Q000494:pharmacology*
D005938:Glucocorticoids; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; C028024:ACTH (4-9); D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone