Memantine protects against secondary neuronal degeneration in lateral geniculate nucleus and superior colliculus after retinal damage in mice.
The purpose of this study, on mice, was to determine whether memantine, a glutamate-receptor antagonist of the N-methyl-(d)-aspartate (NMDA) subtype, protects against neuronal degeneration in the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) after the induction of retinal damage by intravitreal injection of NMDA. NMDA (20 mM/2 microl) was injected into the vitreous body of the left eye in mice (day 0). To evaluate the neuroprotective effect of memantine, mice were assigned to one of two memantine-treated groups: receiving a daily administration of memantine at 30 mg/kg/day, p.o. either from day 0 (administered at 1 h before NMDA injection) to day 90 (pretreated group) or from day 7 to day 90 (post-treated group). The pretreated group exhibited significant suppression of the retinal damage induced by intravitreal injection of NMDA and significant prevention of transsynaptic neuronal degeneration in the dLGN and SC on the contralateral side. Although the mice of the post-treated group displayed no reversion of such retinal damage, they did exhibit protection against neuronal degeneration in the LGN and SC on the contralateral side. These data indicate that memantine can protect against transsynaptic neuronal degeneration in the murine brain (LGN and SC) even if treatment is begun after retinal ganglion cell (RGC) death has started. Memantine protects against the secondary neuronal degeneration in brain regions in the visual pathway that occurs after retinal damage in mice.
Ito
Yasushi
Y
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-Higashi, Gifu 502-8585, Japan.
Nakamura
Shinsuke
S
Tanaka
Hirotaka
H
Shimazawa
Masamitsu
M
Araie
Makoto
M
Hara
Hideaki
H
D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005500:Follow-Up Studies; D005829:Geniculate Bodies / Q000187:drug effects / Q000473:pathology; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012160:Retina / Q000293:injuries / Q000473:pathology; D012164:Retinal Diseases / Q000150:complications* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology; D013477:Superior Colliculi / Q000187:drug effects / Q000473:pathology; D014795:Visual Pathways / Q000187:drug effects* / Q000473:pathology
D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D008559:Memantine
Br J Ophthalmol. 1999 Aug;83(8):980-6
10413706
J Biol Chem. 1999 Aug 6;274(32):22569-80
10428835
Neuropharmacology. 1999 Jun;38(6):735-67
10465680
J Neurosci. 2000 Feb 15;20(4):1333-41
10662823
Arch Ophthalmol. 2000 Mar;118(3):378-84
10721961
Brain Res. 2000 Sep 29;878(1-2):136-47
10996144
Mol Cell Neurosci. 2001 Sep;18(3):247-58
11591126
Exp Eye Res. 2001 Nov;73(5):661-7
11747366
J Comp Neurol. 2002 May 27;447(2):138-51
11977117
Invest Ophthalmol Vis Sci. 2002 Oct;43(10):3319-26
12356841
Arch Ophthalmol. 2003 Feb;121(2):183-8
12583783
N Engl J Med. 2003 Apr 3;348(14):1333-41
12672860
J Pharmacol Exp Ther. 2004 Nov;311(2):677-82
15192085
Invest Ophthalmol Vis Sci. 2004 Aug;45(8):2640-51
15277487
Vis Neurosci. 2005 Sep-Oct;22(5):661-76
16332277
Mol Vis. 2005 Dec 27;11:1173-82
16402025
Br J Ophthalmol. 2006 Jun;90(6):674-8
16464969
Arch Ophthalmol. 2006 Feb;124(2):217-25
16476892
Neuroscience. 2006 Jul 7;140(3):913-28
16626872
Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3975-82
16936113
Mol Vis. 2007 Apr 05;13:578-87
17438523
J Neurosci. 2007 May 9;27(19):5023-32
17494688
J Clin Invest. 2007 Jul;117(7):1763-70
17607354
Neuropsychopharmacology. 2008 Aug;33(9):2228-36
17971830
Eye (Lond). 2007 Dec;21 Suppl 1:S11-4
18157171
Brain Res. 2008 May 30;1212:89-101
18440495
Am J Ophthalmol. 1989 May 15;107(5):453-64
2712129
Neurosci Lett. 1995 Aug 4;195(2):137-9
7478269
N Engl J Med. 1994 Mar 3;330(9):613-22
7905600
Arch Ophthalmol. 1996 Mar;114(3):299-305
8600890
Invest Ophthalmol Vis Sci. 1996 Jul;37(8):1618-24
8675405
Br J Ophthalmol. 1996 May;80(5):389-93
8695555
Eur J Pharmacol. 1996 Feb 5;296(3):239-46
8904075
J Comp Neurol. 1998 Aug 3;397(3):371-93
9674563