Article Text

other Versions

PDF
Minocycline Promotes Dendritic Spine Maturation and Improves Behavioral Performance in the Fragile X Mouse Model
  1. Tina Bilousova (bilousova_tina{at}hotmail.com)
  1. University of California Riverside, United States
    1. Lorraine Dansie (ldans001{at}student.ucr.edu)
    1. University of California Riverside, United States
      1. Michelle Ngo (michellengo517{at}yahoo.com)
      1. University of California Riverside, United States
        1. Jennifer Aye (jaye001{at}student.ucr.edu)
        1. University of California Riverside, United States
          1. Jonathan R Charles (jchar008{at}student.ucr.edu)
          1. University of California Riverside, United States
            1. Douglas W Ethell (doug.ethell{at}ucr.edu)
            1. University of California Riverside, United States
              1. Iryna M Ethell (iryna.ethell{at}ucr.edu)
              1. University of California Riverside, United States

                Abstract

                Background: Fragile X syndrome (FXS) is the most common single-gene inherited form of mental retardation, with behaviors at the extreme of the autistic spectrum. Subjects with FXS and Fragile X mental retardation gene knock out (Fmr1 KO) mice, an animal model for FXS, have been shown to exhibit defects in dendritic spine maturation that may underlie cognitive and behavioral abnormalities in FXS. Minocycline is a tetracycline analog that has been used in clinical trials for stroke, Multiple Sclerosis and several neurodegenerative conditions.

                Methods: We evaluated the effects of minocycline on dendritic spine development in the hippocampus of young Fmr1 KO mice, and in primary cultures of hippocampal neurons isolated from those mice. Cognitive effects of minocycline in young WT and Fmr1 KO mice were also evaluated using established behavioral tests for general cognition, activity and anxiety.

                Results: Our studies demonstrate that minocycline promotes dendritic spine maturation both in cultures and in vivo. The beneficial effects of minocycline on dendritic spine morphology are also accompanied by changes in the behavioral performance of 3-week-old Fmr1 KO mice. Minocycline-treated Fmr1 KO mice show less anxiety in the elevated plus-maze and more strategic exploratory behavior in the Y-maze as compared to untreated Fmr1 KO mice. Our data suggest that these effects of minocycline may relate to its inhibitory action on MMP-9 expression and activity, which are higher in the hippocampus of Fmr1 KO mice.

                Conclusion: These findings establish minocycline as a promising therapeutic for the treatment of Fragile X mental retardation.

                Statistics from Altmetric.com

                Request permissions

                If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.