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Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: Temporal, spatial, and cellular patterns
Author(s) -
Ádori Csaba,
Andó Rómeó D.,
Kovács Gábor G.,
Bagdy György
Publication year - 2006
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/cne.20994
Subject(s) - serotonergic , biology , immunostaining , hippocampus , mdma , endocrinology , medicine , hippocampal formation , neuroscience , serotonin , pharmacology , immunohistochemistry , receptor , biochemistry , immunology
3,4‐Methylenedioxymethamphetamine (MDMA, “ecstasy”) causes long‐term disturbance of the serotonergic system. We examined the temporal, spatial, and cellular distribution of three molecular chaperones, Hsp27, Hsp72, and Hsp90, 3 and 7 days after treatment with 7.5, 15, and 30 mg/kg single intraperitoneal (i.p.) doses of MDMA in Dark Agouti rat brains. Furthermore, we compared the immunostaining patterns of molecular chaperones with serotonergic axonal‐vulnerability evaluated by tryptophan‐hydroxylase (TryOH) immunoreactivity and with astroglial‐activation detected by GFAP‐immunostaining. There was a marked reduction in TryOH‐immunoreactive axon density after MDMA treatment in all examined areas at both time points. Three days after treatment, a significant dose‐dependent increase in Hsp27‐immunoreactive protoplasmic astrocytes was found in the cingulate, frontal, occipital, and pyriform cortex, and in the hippocampus CA1. However, there was no increase in astroglial Hsp27‐immunoreactivity in the caudate putamen, lateral septal nucleus, or anterior hypothalamus. A significant increase in the GFAP immunostaining density of protoplasmic astrocytes was found only in the hippocampus CA1. In addition, numerous strong Hsp72‐immunopositive neurons were found in some brain areas only 3 days after treatment with 30 mg/kg MDMA. Increased Hsp27‐immunoreactivity exclusively in the examined cortical areas reveals that Hsp27 is a sensitive marker of astroglial response to the effects of MDMA in these regions of Dark Agouti rat brain and suggests differential responses in astroglial Hsp27‐expression between distinct brain areas. The co‐occurrence of Hsp27 and GFAP response exclusively in the hippocampus CA1 may suggest the particular vulnerability of this region. The presence of strong Hsp72‐immunopositive neurons in certain brain areas may reflect additional effects of MDMA on nonserotonergic neurons. J. Comp. Neurol. 497:251–269, 2006. © 2006 Wiley‐Liss, Inc.