PMID- 26442661
OWN - NLM
STAT- MEDLINE
DCOM- 20160425
LR  - 20151222
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 136
IP  - 1
DP  - 2016 Jan
TI  - Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic 
      neuron degeneration and neuroinflammation is age-dependent.
PG  - 148-62
LID - 10.1111/jnc.13377 [doi]
AB  - Previous studies have demonstrated that caffeine administration to adult mice 
      potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). 
      As neuroinflammatory response seems to correlate with neurodegeneration, and the 
      young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine 
      neuron degeneration and glial activation in the caudate-putamen (CPu) and 
      substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were 
      treated with MDMA (4 x 20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin 
      (IL)-1beta, tumor necrosis factor (TNF)-alpha, neuronal nitric oxide synthase (nNOS) 
      were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary acidic 
      protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA 
      decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers 
      in CPu were only decreased in adults. In CPu of adolescent mice, caffeine 
      potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b, 
      whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS, 
      IL-1beta, and TNF-alpha were increased by MDMA in CPu of adults, whereas in adolescents, 
      levels were only elevated after combined MDMA plus caffeine. Caffeine alone 
      modified only nNOS. Results suggest that the use of MDMA in association with 
      caffeine during adolescence may exacerbate the neurotoxicity and 
      neuroinflammation elicited by MDMA. Previous studies have demonstrated that 
      caffeine potentiated glial activation induced by 
      3,4-methylenedioxymethamphetamine (MDMA) in adult mice. In this study, caffeine 
      was shown to potentiate MDMA-induced dopamine neuron degeneration in substantia 
      nigra pars compacta, astrogliosis, and TNF-alpha levels in caudate-putamen of 
      adolescent mice. Results suggest that combined use of MDMA plus caffeine during 
      adolescence may worsen the neurotoxicity and neuroinflammation elicited by MDMA.
CI  - (c) 2015 International Society for Neurochemistry.
FAU - Frau, Lucia
AU  - Frau L
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Cagliari, Italy.
FAU - Costa, Giulia
AU  - Costa G
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Cagliari, Italy.
FAU - Porceddu, Pier Francesca
AU  - Porceddu PF
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Cagliari, Italy.
FAU - Khairnar, Amit
AU  - Khairnar A
AD  - Applied Neuroscience Research Group, CEITEC - Central European Institute of 
      Technology, Masaryk University, Brno, Czech Republic.
FAU - Castelli, Maria Paola
AU  - Castelli MP
AD  - Department of Biomedical Sciences, Section of Neuroscience and Clinical 
      Pharmacology, University of Cagliari, Monserrato (CA), Italy.
FAU - Ennas, Maria Grazia
AU  - Ennas MG
AD  - Department of Biomedical Sciences, Section of Neuroscience and Clinical 
      Pharmacology, University of Cagliari, Monserrato (CA), Italy.
FAU - Madeddu, Camilla
AU  - Madeddu C
AD  - Department of Biomedical Sciences, Section of Neuroscience and Clinical 
      Pharmacology, University of Cagliari, Monserrato (CA), Italy.
FAU - Wardas, Jadwiga
AU  - Wardas J
AD  - Department of Neuropsychopharmacology, Institute of Pharmacology, Polish Academy 
      of Sciences, Krakow, Poland.
FAU - Morelli, Micaela
AU  - Morelli M
AD  - Department of Biomedical Sciences, Section of Neuropsychopharmacology, University 
      of Cagliari, Cagliari, Italy.
AD  - CNR, Institute of Neuroscience, Cagliari, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151106
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 3G6A5W338E (Caffeine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Age Factors
MH  - Aging/*drug effects/pathology
MH  - Animals
MH  - Caffeine/administration & dosage/*toxicity
MH  - Dopaminergic Neurons/*drug effects/pathology
MH  - Drug Synergism
MH  - Inflammation/chemically induced/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity
MH  - Nerve Degeneration/*chemically induced/pathology
OTO - NOTNLM
OT  - adolescence
OT  - caudate-putamen
OT  - cytokines
OT  - nitric oxide
OT  - substantia nigra
OT  - tyrosine hydroxylase
EDAT- 2015/10/08 06:00
MHDA- 2016/04/26 06:00
CRDT- 2015/10/08 06:00
PHST- 2015/07/01 00:00 [received]
PHST- 2015/09/02 00:00 [revised]
PHST- 2015/09/03 00:00 [accepted]
PHST- 2015/10/08 06:00 [entrez]
PHST- 2015/10/08 06:00 [pubmed]
PHST- 2016/04/26 06:00 [medline]
AID - 10.1111/jnc.13377 [doi]
PST - ppublish
SO  - J Neurochem. 2016 Jan;136(1):148-62. doi: 10.1111/jnc.13377. Epub 2015 Nov 6.