Effects of Chronic Minocycline Treatment on Neurogenesis in Fmr1 KO Mice

Date

2016-04-27

Authors

Yang, Yuebo
Yau, Suk-Yu
Chiu, Christine
Christie, Brian R.

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Abstract

Fragile X syndrome (FXS) is an X-linked genetic disorder resulting from over-expansion of CGG trinucleotide repeats within the Fragile X Mental Retardation 1 (Fmr1) gene, inhibiting the activity of its transcript, Fragile X Mental Retardation protein (FMRP) (Garber et al. 2008). FMRP has been shown to regulate translation by binding a subset of mRNAs important in synaptic plasticity, and therefore plays an important role in cognitive development (Barber et al. 2008). Thus, those with FXS suffer cognitive disabilities, including learning and memory loss (Terracciano et al. 2005). Minocycline is a drug traditionally used in bacterial infections (Brogden et al. 1975). In recent literature minocycline has been shown to possess neuroprotective ability in common neurological diseases (Plane et al. 2010) such as Parkinson’s and Huntington’s diseases, as well as FXS. Furthermore, our own behavioral tests using minocycline-treated FXS mice show improved learning and memory compared to controls. However, the methodology behind these improved cognitive functions in minocycline treated FXS mouse models (Fmr1 KO mice) is lacking in literature and requires further studies. In this experiment we investigate neurogenesis, the growth and development of nervous tissue, via cell proliferation and neuronal differentiation in the dentate gyrus (DG) of minocycline treated Fmr1 KO mice as a possible mechanism for the improved cognitive functions. We hypothesize that minocycline could up-regulate cell proliferation and or neuronal differentiation in the DG, and we investigate this by staining Ki67, PCNA, and DCX positive cells using immunohistochemistry then counting these in a manual sample-blinded manner. Cell counts for minocycline treated Fmr1 KO mice are compared to water-treated/ wild-type littermate controls.

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Keywords

Ki67, PCNA, DXC, Minocycline, Fragile-X

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