Adaptive Plasticity in the Hippocampus of Young Mice Intermittently Exposed to MDMA Could Be the Origin of Memory Deficits

Autor: Jorge Camarasa, Elena Escubedo, David Pubill, Sonia Abad, Antoni Camins
Přispěvatelé: Universitat de Barcelona
Rok vydání: 2015
Předmět:
Male
0301 basic medicine
Aging
medicine.medical_specialty
Tyrosine 3-Monooxygenase
Ratolins (Animals de laboratori)
N-Methyl-3
4-methylenedioxyamphetamine
Hipocamp (Cervell)
Neuroscience (miscellaneous)
Hippocampus
Substantia nigra
Striatum
Hippocampal formation
03 medical and health sciences
Cellular and Molecular Neuroscience
Ecstasy (Drug)
0302 clinical medicine
Memory
Dopamine
Internal medicine
medicine
Animals
RNA
Messenger
Neurons
Brain-derived neurotrophic factor
Memory Disorders
Neuronal Plasticity
Brain-Derived Neurotrophic Factor
Amphetamines
Dopaminergic
Èxtasi (Droga)
Trastorns de la memòria
MDMA
Amfetamines
Mice
Inbred C57BL
Mice (Laboratory animals)
030104 developmental biology
Endocrinology
Neurology
Memory disorders
Hippocampus (Brain)
Psychology
Proto-Oncogene Proteins c-fos
Neuroscience
Biomarkers
030217 neurology & neurosurgery
medicine.drug
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Europe PubMed Central
Recercat. Dipósit de la Recerca de Catalunya
instname
ISSN: 1559-1182
0893-7648
DOI: 10.1007/s12035-015-9618-z
Popis: (±)3,4-Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. This study was designed to evaluate whether MDMA exposure affects their recognition memory and hippocampal expression of plasticity markers. Mice were administered with increasing doses of MDMA once per week for 8 weeks (three times in 1 day, every 3 h) and killed 2 weeks (2w) or 3 months (3m) later. The treatment did not modify hippocampal tryptophan hydroxylase 2, a serotonergic indicator, but induced an initial reduction in dopaminergic markers in substantia nigra, which remained stable for at least 3 months. In parallel, MDMA produced a decrease in dopamine (DA) levels in the striatum at 2w, which were restored 3 months later, suggesting dopaminergic terminal regeneration (sprouting phenomenon). Moreover, recognition memory was assessed using the object recognition test. Young (2w) and mature (3m) adult mice exhibited impaired memory after 24-h but not after just 1-h retention interval. Two weeks after the treatment, animals showed constant levels of CREB but an increase in its phosphorylated form and in c-Fos expression. Brain-derived neurotrophic factor (BDNF) and especially Arc overexpression was sustained and long-lasting. We cannot rule out the absence of MDMA injury in the hippocampus being due to the generation of BDNF. The levels of NMDAR2B, PSD-95, and synaptophysin were unaffected. In conclusion, the young mice exposed to MDMA showed increased expression of early key markers of plasticity, which sometimes remained for 3 months, and suggests hippocampal maladaptive plasticity that could explain memory deficits evidenced here.
Databáze: OpenAIRE
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