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
Csaba Ádori, Rómeó D. Andó, Gábor G. Kovács, György Bagdy
The Journal of Comparative Neurology 2006 DOI: 10.1002/cne.20994 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experiment Peer reviewed |
|---|---|
| Population | Dark Agouti rat brains |
| Intervention | MDMA |
| Dose | 7.5, 15, and 30 mg/kg single intraperitoneal (i.p.) doses |
| Duration | 3 and 7 days after treatment |
| Topics | MDMA Serotonin |
| Keywords | Immunostaining Hippocampus Endocrinology Hippocampal formation |
| Citations | 51 |
| Key findings | MDMA caused a dose-dependent increase in Hsp27-immunoreactive protoplasmic astrocytes in cortical areas and hippocampus CA1, with co-occurrence of Hsp27 and GFAP response only in hippocampus CA1, suggesting regional differences in astroglial response and particular vulnerability of the hippocampus CA1. |
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 22
- The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis Current Neuropharmacology March 1, 2011
- Effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: implications for MDMA neurotoxicity Journal of Neurochemistry November 30, 2009
- Enzymatic–nonenzymatic cellular antioxidant defense systems response and immunohistochemical detection of MDMA, VMAT2, HSP70, and apoptosis as biomarkers for MDMA (Ecstasy) neurotoxicity Journal of Neuroscience Research October 1, 2009
- Recovery and aging of serotonergic fibers after single and intermittent MDMA treatment in dark agouti rat The Journal of Comparative Neurology March 31, 2011
- Effects of Stress and MDMA on Hippocampal Gene Expression BioMed Research International 2014
and 17 more in the library
Cites 15
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- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype British Journal of Pharmacology August 1, 1995
- The Role of Metabolism in 3,4-(±)-Methylenedioxyamphetamine and 3,4-(±)-Methylenedioxymethamphetamine (Ecstasy) toxicity Therapeutic Drug Monitoring March 19, 2004
- Cutaneous Vasoconstriction Contributes to Hyperthermia Induced by 3,4-Methylenedioxymethamphetamine (Ecstasy) in Conscious Rabbits Journal of Neuroscience November 1, 2001
and 10 more in the library