Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation

被引:175
作者
Riazi, Kiarash
Galic, Michael A.
Kentner, Amanda C.
Reid, Aylin Y.
Sharkey, Keith A.
Pittman, Quentin J. [1 ]
机构
[1] Univ Calgary, Cumming Sch Med, Dept Physiol & Pharmacol, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada
基金
加拿大健康研究院;
关键词
cytokine; glutamate; LTD; LTP; microglia; neuroinflammation; LONG-TERM POTENTIATION; CHRONIC LIVER-DISEASE; QUALITY-OF-LIFE; AMPA RECEPTOR; NMDA RECEPTORS; TNF-ALPHA; IN-VIVO; MESSENGER-RNA; NR2B SUBUNIT; BRAIN;
D O I
10.1523/JNEUROSCI.4485-14.2015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Peripheral inflammatory diseases are often associated with behavioral comorbidities including anxiety, depression, and cognitive dysfunction, but the mechanism for these is not well understood. Changes in the neuronal and synaptic functions associated with neuroinflammation may underlie these behavioral abnormalities. We have used a model of colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid in Sprague Dawley rats to identify inflammation-induced changes in hippocampal synaptic transmission. Hippocampal slices obtained 4 d after the induction of inflammation revealed enhanced Schaffer collateral-induced excitatory field potentials in CA1 stratum radiatum. This was associated with larger-amplitude mEPSCs, but unchanged mEPSC frequencies and paired-pulse ratios, suggesting altered postsynaptic effects. Both AMPA-and NMDA-mediated synaptic currents were enhanced, and analysis of AMPA-mediated currents revealed increased contributions of GluR2-lacking receptors. In keeping with this, both transcripts and protein levels of the GluR2 subunit were reduced in hippocampus. Both long-term potentiation (LTP) and depression (LTD) were significantly reduced in hippocampal slices taken from inflamed animals. Chronic administration of the microglial/macrophage activation inhibitor minocycline to the inflamed animals both lowered the level of the cytokine tumor necrosis factor alpha in the hippocampus and completely abolished the effect of peripheral inflammation on the field potentials and synaptic plasticity (LTP and LTD). Our results reveal profound synaptic changes caused by a mirror microglia-mediated inflammatory response in hippocampus during peripheral organ inflammation. These synaptic changes may underlie the behavioral comorbidities seen in patients.
引用
收藏
页码:4942 / 4952
页数:11
相关论文
共 90 条
[81]   Peripheral inflammation is associated with remote global gene expression changes in the brain [J].
Thomson, Carolyn A. ;
McColl, Alison ;
Cavanagh, Jonathan ;
Graham, Gerard J. .
JOURNAL OF NEUROINFLAMMATION, 2014, 11
[82]   EFFECTS OF A SPIDER TOXIN AND ITS ANALOG ON GLUTAMATE-ACTIVATED CURRENTS IN THE HIPPOCAMPAL CA1 NEURON AFTER ISCHEMIA [J].
TSUBOKAWA, H ;
OGURO, K ;
MASUZAWA, T ;
NAKAIMA, T ;
KAWAI, N .
JOURNAL OF NEUROPHYSIOLOGY, 1995, 74 (01) :218-225
[83]   Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons [J].
Ungless, MA ;
Whistler, JL ;
Malenka, RC ;
Bonci, A .
NATURE, 2001, 411 (6837) :583-587
[84]   Epilepsy and brain inflammation [J].
Vezzani, Annamaria ;
Aronica, Eleonora ;
Mazarati, Andrey ;
Pittman, Quentin J. .
EXPERIMENTAL NEUROLOGY, 2013, 244 :11-21
[85]   Switch to Ca2+-permeable AMPA and reduced NR2B NMDA receptor-mediated neurotransmission at dorsal horn nociceptive synapses during inflammatory pain in the rat [J].
Vikman, Kristina S. ;
Rycroft, Beth K. ;
Christie, Macdonald J. .
JOURNAL OF PHYSIOLOGY-LONDON, 2008, 586 (02) :515-527
[86]   Neuroinflammation and Comorbidity of Pain and Depression [J].
Walker, A. K. ;
Kavelaars, A. ;
Heijnen, C. J. ;
Dantzer, R. .
PHARMACOLOGICAL REVIEWS, 2014, 66 (01) :80-101
[87]   NMDA Receptor Blockade by Ketamine Abrogates Lipopolysaccharide-Induced Depressive-Like Behavior in C57BL/6J Mice [J].
Walker, Adam K. ;
Budac, David P. ;
Bisulco, Stephanie ;
Lee, Anna W. ;
Smith, Robin A. ;
Beenders, Brent ;
Kelley, Keith W. ;
Dantzer, Robert .
NEUROPSYCHOPHARMACOLOGY, 2013, 38 (09) :1609-1616
[88]   A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning [J].
Wiltgen, Brian J. ;
Royle, Gordon A. ;
Gray, Erin E. ;
Abdipranoto, Andrea ;
Thangthaeng, Nopporn ;
Jacobs, Nate ;
Saab, Faysal ;
Tonegawa, Susumu ;
Heinemann, Stephen F. ;
O'Dell, Thomas J. ;
Fanselow, Michael S. ;
Vissel, Bryce .
PLOS ONE, 2010, 5 (09)
[89]   Upregulation of forebrain NMDA NR2B receptors contributes to behavioral sensitization after inflammation [J].
Wu, LJ ;
Toyoda, H ;
Zhao, MG ;
Lee, YS ;
Tang, JR ;
Ko, SW ;
Jia, YH ;
Shum, FWF ;
Zerbinatti, CV ;
Bu, GJ ;
Wei, F ;
Xu, TL ;
Muglia, LJ ;
Chen, ZF ;
Auberson, YP ;
Kaang, BK ;
Zhuo, M .
JOURNAL OF NEUROSCIENCE, 2005, 25 (48) :11107-11116
[90]   Short-term synaptic plasticity [J].
Zucker, RS ;
Regehr, WG .
ANNUAL REVIEW OF PHYSIOLOGY, 2002, 64 :355-405