title: Long-lasting effects of minocycline on behavior in young but not adult Fragile X mice.
abstract: Fragile X Syndrome (FXS) is the most common single-gene inherited form of intellectual disability with behaviors characteristic of autism. People with FXS display childhood seizures, hyperactivity, anxiety, developmental delay, attention deficits, and visual-spatial memory impairment, as well as a propensity for obsessive-compulsive disorder. Several of these aberrant behaviors and FXS-associated synaptic irregularities also occur in "fragile X mental retardation gene" knock-out (Fmr1 KO) mice. We previously reported that minocycline promotes the maturation of dendritic spines - postsynaptic sites for excitatory synapses - in the developing hippocampus of Fmr1 KO mice, which may underlie the beneficial effects of minocycline on anxiolytic behavior in young Fmr1 KO mice. In this study, we compared the effectiveness of minocycline treatment in young and adult Fmr1 KO mice, and determined the dependence of behavioral improvements on short-term versus long-term minocycline administration. We found that 4- and 8-week-long treatments significantly reduced locomotor activity in both young and adult Fmr1 KO mice. Some behavioral improvements persisted in young mice post-treatment, but in adults the beneficial effects were lost soon after minocycline treatment was stopped. We also show, for the first time, that minocycline treatment partially attenuates the number and severity of audiogenic seizures in Fmr1 KO mice. This report provides further evidence that minocycline treatment has immediate and long-lasting benefits on FXS-associated behaviors in the Fmr1 KO mouse model.
authors: Division of Biomedical Sciences, Biochemistry and Molecular Biology Program, University of California Riverside, Riverside, CA 92521, USA.
authors: L E
authors: LE
authors: Dansie
authors: K
authors: K
authors: Phommahaxay
authors: A G
authors: AG
authors: Okusanya
authors: J
authors: J
authors: Uwadia
authors: M
authors: M
authors: Huang
authors: S E
authors: SE
authors: Rotschafer
authors: K A
authors: KA
authors: Razak
authors: D W
authors: DW
authors: Ethell
authors: I M
authors: IM
authors: Ethell
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D005600:Fragile X Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D008911:Minocycline; C497684:Fmr1 protein, mouse
references: Psychoneuroendocrinology. 2008 Jul;33(6):883-9
references: 18479837
references: J Dev Behav Pediatr. 2013 Apr;34(3):147-55
references: 23572165
references: BMC Neurol. 2010 Oct 11;10:91
references: 20937127
references: Cereb Cortex. 2000 Oct;10(10):981-91
references: 11007549
references: PLoS One. 2010 Mar 16;5(3):e9706
references: 20300527
references: J Neurosci. 2004 May 19;24(20):4859-64
references: 15152046
references: Behav Pharmacol. 1995 Jan;6(1):24-31
references: 11224308
references: J Cell Sci. 2011 Oct 1;124(Pt 19):3369-80
references: 21896646
references: Prog Neurobiol. 2005 Feb;75(3):161-205
references: 15882774
references: J Neurosci. 2010 Jan 13;30(2):694-702
references: 20071534
references: Epilepsia. 2000 Jan;41(1):19-23
references: 10643918
references: Case Rep Genet. 2012;2012:280813
references: 23074686
references: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7101-6
references: 11416194
references: Learn Mem. 2007 Sep 25;14(10):655-64
references: 17909100
references: Psychopharmacology (Berl). 2009 Jun;204(2):361-73
references: 19189082
references: J Neurochem. 2004 Dec;91(5):1219-30
references: 15569265
references: Neuron. 2007 Dec 20;56(6):955-62
references: 18093519
references: Neuroscientist. 2009 Oct;15(5):549-67
references: 19325170
references: Genes Brain Behav. 2004 Dec;3(6):337-59
references: 15544577
references: J Biol Chem. 1998 Jun 19;273(25):15521-7
references: 9624140
references: Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19520-5
references: 19047646
references: Pharmacol Biochem Behav. 1986 Mar;24(3):525-9
references: 2871560
references: PLoS One. 2010 Nov 08;5(11):e15430
references: 21151481
references: Neural Plast. 2012;2012:124548
references: 22685676
references: Brain Res. 2008 Jan 10;1188:241-53
references: 18022143
references: Annu Rev Neurosci. 2001;24:1071-89
references: 11520928
references: Brain Res. 2009 Dec 1;1300:146-58
references: 19748497
references: Neurosci Biobehav Rev. 2005;29(8):1193-205
references: 16084592
references: Biol Psychiatry. 2007 Aug 15;62(4):359-62
references: 17210139
references: J Neurosci. 2007 Dec 26;27(52):14349-57
references: 18160642
references: Biochem Pharmacol. 2010 Feb 15;79(4):632-46
references: 19799873
references: J Med Genet. 2009 Feb;46(2):94-102
references: 18835858
references: J Neurosci. 2012 Oct 17;32(42):14538-47
references: 23077039
references: Neuropharmacology. 2009 Feb;56(2):463-72
references: 18952114
references: Curr Opin Neurobiol. 2006 Jun;16(3):265-9
references: 16707258
references: Trends Neurosci. 2005 Apr;28(4):182-7
references: 15808352
references: J Cereb Blood Flow Metab. 2006 Sep;26(9):1157-64
references: 16395286
references: J Neurosci. 2006 Feb 22;26(8):2167-73
references: 16495443
references: Biochem Cell Biol. 1999;77(4):331-42
references: 10546896
references: Brain Res. 2012 Feb 23;1439:7-14
references: 22265702
references: Genes Brain Behav. 2005 Jun;4(4):240-52
references: 15924556
references: Neuron Glia Biol. 2004 Aug;1(3):297-305
references: 18634603
references: Psychopharmacology (Berl). 1994 May;114(4):597-600
references: 7855221
references: Am J Intellect Dev Disabil. 2010 Sep;115(5):433-43
references: 20687826
references: J Pineal Res. 2009 Mar;46(2):224-34
references: 19141086
references: J Neurosci. 2004 Jul 14;24(28):6352-61
references: 15254091
references: Epilepsia. 1999 Aug;40(8):1092-9
references: 10448821
references: Mol Autism. 2010 Sep 21;1(1):12
references: 20858229
references: Cell. 2011 Jul 22;146(2):247-61
references: 21784246
references: J Cell Biol. 2008 Mar 10;180(5):1021-35
references: 18332222
references: Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4429-34
references: 18332424
references: J Neurophysiol. 2007 Jul;98(1):334-44
references: 17493927
references: Psychopharmacologia. 1973 Aug 3;31(4):305-20
references: 4582344
references: Semin Arthritis Rheum. 1999 Jun;28(6):392-7
references: 10406406
references: Eur J Neurosci. 2005 Jul;22(1):21-7
references: 16029192
references: Am J Med Genet A. 2013 Aug;161A(8):1897-903
references: 23824974
references: Brain Res Brain Res Rev. 2002 Jun;39(1):29-54
references: 12086707
references: J Neurosci. 2006 Jul 5;26(27):7151-5
references: 16822971
references: Eur J Pharmacol. 2003 Feb 28;463(1-3):3-33
references: 12600700
references: Neuropharmacology. 2005 Dec;49(7):1053-66
references: 16054174
references: Circ Res. 2004 Aug 20;95(4):364-71
references: 15256478
references: J Neurosci. 2006 Feb 15;26(7):1923-34
references: 16481424
references: Curr Opin Neurobiol. 1999 Jun;9(3):343-8
references: 10395574
references: J Neuropathol Exp Neurol. 2009 Dec;68(12):1309-18
references: 19915485
references: Neuron. 2006 Aug 17;51(4):441-54
references: 16908410
references: Dis Model Mech. 2011 Sep;4(5):673-85
references: 21669931
references: Prog Neuropsychopharmacol. 1981;5(2):159-65
references: 6115434
references: Autism Res. 2011 Feb;4(1):40-56
references: 21268289
references: Rheumatology (Oxford). 2001 Mar;40(3):329-35
references: 11285382
references: Br J Pharmacol. 2008 Mar;153 Suppl 1:S428-37
references: 18311157
references: Pharmacol Biochem Behav. 1991 Jan;38(1):63-7
references: 2017455
references: Acta Neuropathol. 1985;67(3-4):289-95
references: 4050344