Prostaglandin E2-induced synaptic plasticity in neocortical networks of organotypic slice cultures.
Traumatic brain injury (TBI) is a major cause of epilepsy, yet the mechanisms underlying the progression from TBI to epilepsy are unknown. TBI induces the expression of COX-2 (cyclooxygenase-2) and increases levels of prostaglandin E2 (PGE2). Here, we demonstrate that acutely applied PGE2 (2 mum) decreases neocortical network activity by postsynaptically reducing excitatory synaptic transmission in acute and organotypic neocortical slices of mice. In contrast, long-term exposure to PGE2 (2 mum; 48 h) presynaptically increases excitatory synaptic transmission, leading to a hyperexcitable network state that is characterized by the generation of paroxysmal depolarization shifts (PDSs). PDSs were also evoked as a result of depriving organotypic slices of activity by treating them with tetrodotoxin (TTX, 1 mum; 48 h). This treatment predominantly increased postsynaptically excitatory synaptic transmission. The network and cellular effects of PGE2 and TTX treatments reversed within 1 week. Differences in the underlying mechanisms (presynaptic vs postsynaptic) as well as occlusion experiments in which slices were exposed to TTX plus PGE2 suggest that the two substances evoke distinct forms of homeostatic plasticity, both of which result in a hyperexcitable network state. PGE2 and TTX (alone or together with PGE2) also increased levels of apoptotic cell death in organotypic slices. Thus, we hypothesize that the increase in excitability and apoptosis may constitute the first steps in a cascade of events that eventually lead to epileptogenesis triggered by TBI.
Koch
Henner
H
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington 98101, USA. henner.koch@seattlechildrens.org
Huh
Sung-Eun
SE
Elsen
Frank P
FP
Carroll
Michael S
MS
Hodge
Rebecca D
RD
Bedogni
Francesco
F
Turner
Michael S
MS
Hevner
Robert F
RF
Ramirez
Jan-Marino
JM
D000818:Animals; D000831:Animals, Newborn; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D015232:Dinoprostone
Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2317-21
8637870
Cereb Cortex. 2008 Jun;18(6):1335-49
17965127
Mol Cell Neurosci. 2008 Apr;37(4):682-95
18295507
Annu Rev Physiol. 2001;63:847-69
11181978
J Neurosci. 2008 Apr 23;28(17):4377-84
18434516
J Neurosci. 1997 Mar 15;17(6):2168-80
9045741
Nature. 1993 Apr 15;362(6421):640-2
8385275
J Neurosci. 2010 Mar 24;30(12):4440-8
20335480
Science. 2002 Mar 22;295(5563):2282-5
11910117
J Neurosci. 1995 Jan;15(1 Pt 2):604-22
7823167
Neuron. 2008 Nov 6;60(3):477-82
18995822
J Neurophysiol. 2006 Oct;96(4):2127-33
16760351
J Neurosci. 2008 Jul 2;28(27):6760-72
18596152
J Neurophysiol. 2003 Sep;90(3):1571-80
12750417
Neuron. 2008 May 22;58(4):472-97
18498731
Seizure. 2000 Oct;9(7):453-7
11034867
Neurology. 1985 Oct;35(10):1406-14
3929158
Neuron. 1993 Aug;11(2):371-86
8352945
J Neurophysiol. 2005 Feb;93(2):929-41
15653788
J Neurophysiol. 2001 Mar;85(3):1067-77
11247977
J Neurosci. 2009 Feb 18;29(7):2103-12
19228963
Nature. 2006 Apr 20;440(7087):1054-9
16547515
J Neurosci. 2008 Apr 2;28(14):3707-17
18385329
Arch Phys Med Rehabil. 2003 Mar;84(3):365-73
12638104
Neuron. 2009 Feb 12;61(3):340-50
19217372
PLoS One. 2007 Aug 01;2(7):e670
17668052
Eur J Neurosci. 2003 Aug;18(3):486-96
12911745
J Neurophysiol. 2006 Nov;96(5):2564-77
16870839
J Clin Neurophysiol. 2007 Apr;24(2):154-64
17414971
Methods Enzymol. 1992;207:100-22
1528114
J Neurophysiol. 1993 Apr;69(4):1276-91
8492163
J Neurosci. 2006 Oct 4;26(40):10209-21
17021176
J Neurophysiol. 2006 Feb;95(2):902-13
16236784
Arch Ital Biol. 2001 Feb;139(1-2):37-51
11256186
J Neurosci. 2007 May 30;27(22):5915-25
17537962
Nature. 1998 Feb 26;391(6670):892-6
9495341
Cereb Cortex. 2005 Jun;15(6):834-45
15483049
Neuron. 2001 Feb;29(2):353-66
11239428
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1924-9
11172052
Nat Neurosci. 2002 Jan;5(1):34-40
11740501
Int J Dev Neurosci. 2007 Jun;25(4):233-41
17459648
Dev Neurosci. 2000;22(1-2):125-38
10657705
Neuroscience. 1990;39(2):451-8
2087266
J Head Trauma Rehabil. 2006 Sep-Oct;21(5):398-402
16983225
J Neurosci. 2007 Feb 14;27(7):1746-55
17301182
J Neurosci. 2006 Nov 29;26(48):12587-95
17135420
Nat Neurosci. 2000 Oct;3(10):1027-34
11017176
Nat Neurosci. 1999 Jun;2(6):515-20
10448215
Neuron. 2003 Aug 28;39(5):831-42
12948449
Neuron. 1998 Nov;21(5):1067-78
9856462
Nature. 2006 Sep 7;443(7107):81-4
16929304
J Neurosci. 2005 Oct 26;25(43):9858-70
16251433
J Neurosci. 2006 Apr 26;26(17):4535-45
16641233