title: 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.
abstract: 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.
authors.affiliation: Laboratory of Neurochemistry and Experimental Medicine, National Institute of Psychiatry and Neurology, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Adori
authors.forename: Rómeó D
authors.initials: RD
authors.lastname: Andó
authors.forename: Gábor G
authors.initials: GG
authors.lastname: Kovács
authors.forename: György
authors.initials: G
authors.lastname: Bagdy
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage*; D009363:Neoplasm Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D055551:HSP27 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D018490:Serotonin Agents; D012701:Serotonin; D014446:Tyrosine 3-Monooxygenase; D018817:N-Methyl-3,4-methylenedioxyamphetamine