PMID- 23973311
OWN - NLM
STAT- MEDLINE
DCOM- 20140605
LR  - 20131021
IS  - 1873-7064 (Electronic)
IS  - 0028-3908 (Linking)
VI  - 76 Pt A
DP  - 2014 Jan
TI  - Zonisamide regulates basal ganglia transmission via astroglial kynurenine 
      pathway.
PG  - 137-45
LID - S0028-3908(13)00359-6 [pii]
LID - 10.1016/j.neuropharm.2013.08.002 [doi]
AB  - To clarify the anti-parkinsonian mechanisms of action of zonisamide (ZNS), we 
      determined the effects of ZNS on tripartite synaptic transmission associated with 
      kynurenine (KYN) pathway (KP) in cultured astrocytes, and transmission in both 
      direct and indirect pathways of basal ganglia using microdialysis. Interactions 
      between cytokines [interferon-gamma (IFNgamma) and tumor-necrosis factor-alpha (TNFalpha)] and 
      ZNS on astroglial releases of KP metabolites, KYN, kynurenic-acid (KYNA), 
      xanthurenic-acid (XTRA), cinnabarinic-acid (CNBA) and quinolinic-acid (QUNA), 
      were determined by extreme liquid-chromatography with mass-spectrometry. 
      Interaction among metabotropic glutamate-receptor (mGluR), KP metabolites and ZNS 
      on striato-nigral, striato-pallidal GABAergic and subthalamo-nigral glutamatergic 
      transmission was examined by microdialysis with extreme liquid-chromatography 
      fluorescence resonance-energy transfer detection. Acute and chronic ZNS 
      administration increased astroglial release of KYN, KYNA, XTRA and CNBA, but not 
      QUNA. Chronic IFNgamma administration increased the release of KYN, KYNA, CNBA and 
      QUNA, but had minimal inhibitory effect on XTRA release. Chronic TNFalpha 
      administration increased CNBA and QUNA, but not KYN, KYNA or XTRA. ZNS inhibited 
      IFNgamma-induced elevation of KYN, KYNA and QUNA, but enhanced IFNgamma-induced that of 
      CNBA. TNFalpha-induced rises in CNBA and QUNA were inhibited by ZNS. ZNS inhibited 
      striato-nigral GABAergic, striato-pallidal GABAergic and subthalamo-nigral 
      glutamatergic transmission via activation of groups II and III mGluRs. ZNS 
      enhanced astroglial release of endogenous agonists of group II mGluR, XTRA and 
      group III mGluR, CNBA. Activated endogenous mGluR agonists inhibited transmission 
      in direct and indirect pathways of basal ganglia. These mechanisms contribute to 
      effectiveness and well tolerability of ZNS as an adjunct treatment for 
      Parkinson's disease during l-DOPA monotherapy. This article is part of the 
      Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Fukuyama, Kouji
AU  - Fukuyama K
AD  - Department of Neuropsychiatry, Division of Neuroscience, Graduate School of 
      Medicine, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
FAU - Tanahashi, Shunske
AU  - Tanahashi S
FAU - Hoshikawa, Masamitsu
AU  - Hoshikawa M
FAU - Shinagawa, Rika
AU  - Shinagawa R
FAU - Okada, Motohiro
AU  - Okada M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130822
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (metabotropic glutamate receptor 2)
RN  - 0 (metabotropic glutamate receptor 3)
RN  - 343-65-7 (Kynurenine)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism
MH  - Basal Ganglia/*drug effects/physiology
MH  - Drug Interactions
MH  - Interferon-gamma/pharmacology
MH  - Kynurenine/drug effects/*metabolism
MH  - Neural Pathways/drug effects/metabolism
MH  - Primary Cell Culture
MH  - Rats
MH  - Receptors, Metabotropic Glutamate/agonists
MH  - Signal Transduction/*drug effects
MH  - Substantia Nigra/drug effects/metabolism
MH  - Synaptic Transmission/*drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
OTO - NOTNLM
OT  - Astrocyte
OT  - Cinnabarinic acid
OT  - Kynurenine pathway
OT  - Parkinson's disease
OT  - Xanthurenic acid
OT  - Zonisamide
EDAT- 2013/08/27 06:00
MHDA- 2014/06/06 06:00
CRDT- 2013/08/27 06:00
PHST- 2013/02/25 00:00 [received]
PHST- 2013/08/01 00:00 [revised]
PHST- 2013/08/08 00:00 [accepted]
PHST- 2013/08/27 06:00 [entrez]
PHST- 2013/08/27 06:00 [pubmed]
PHST- 2014/06/06 06:00 [medline]
AID - S0028-3908(13)00359-6 [pii]
AID - 10.1016/j.neuropharm.2013.08.002 [doi]
PST - ppublish
SO  - Neuropharmacology. 2014 Jan;76 Pt A:137-45. doi: 
      10.1016/j.neuropharm.2013.08.002. Epub 2013 Aug 22.