Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits - PubMed (original) (raw)

Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits

T A Comery et al. Proc Natl Acad Sci U S A. 1997.

Abstract

Fragile X syndrome arises from blocked expression of the fragile X mental retardation protein (FMRP). Golgi-impregnated mature cerebral cortex from fragile X patients exhibits long, thin, tortuous postsynaptic spines resembling spines observed during normal early neocortical development. Here we describe dendritic spines in Golgi-impregnated cerebral cortex of transgenic fragile X gene (Fmr1) knockout mice that lack expression of the protein. Dendritic spines on apical dendrites of layer V pyramidal cells in occipital cortex of fragile X knockout mice were longer than those in wild-type mice and were often thin and tortuous, paralleling the human syndrome and suggesting that FMRP expression is required for normal spine morphological development. Moreover, spine density along the apical dendrite was greater in the knockout mice, which may reflect impaired developmental organizational processes of synapse stabilization and elimination or pruning.

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Figures

Figure 1

Figure 1

Golgi-Cox impregnated apical dendrites in transgenic and wild-type mice. (A) Segment of apical dendrite from layer V pyramidal neuron in Fmr1 knockout mouse demonstrating both the increased incidence of long, thin dendritic spines and the increased spine density. (B) Apical dendrite of layer V pyramidal neuron from wild-type mouse. (Bar = 10 μm.)

Figure 2

Figure 2

Mean dendritic length (and SEM) of spines on apical dendrites of layer V pyramidal neurons in visual cortex from knockout (KO) and wild-type mice. Dendritic spines in Fmr1 transgenic mice were significantly longer than those in the wild-type animals (one-tailed t test; t = 2.25, df = 6, P = 0.033).

Figure 3

Figure 3

Number of spines in each reticule-based length category on apical dendrites of layer V pyramidal neurons in visual cortex from knockout (KO) and wild-type mice. Knockout mice have fewer short spines and more long spines (χ2 = 46.29, 3 df, P < .0005).

Figure 4

Figure 4

Mean spine density (and SEM) distributions in fragile X knockout (KO) and wild-type mice. Overall spine density along apical dendrites of layer V pyramidal cells is significantly greater in knockout mice than in wild-type controls (F1,33 = 63.3, P < 0.0001). Dotted lines in graphs indicate reduced numbers of dendrites in the analysis due to some apical dendrites having been truncated by the section plane.

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References

    1. Hagerman R J, Cronister A, editors. Fragile X Syndrome: Diagnosis, Treatment, and Research. 2nd Ed. Baltimore: Johns Hopkins Univ. Press; 1996.
    1. Warren S T, Nelson D L. J Am Med Assoc. 1994;271:536–542. - PubMed
    1. Brown W T. Am J Hum Genet. 1996;58:903–905. - PMC - PubMed
    1. Verheij C, Bakker C E, de Graaff E, Keulemans J, Willemsen R, Verkerk A J, Galjaard H, Reuser A J, Hoogeveen A T, Oostra B A. Nature (London) 1993;363:722–724. - PubMed
    1. Verkerk A J M H, Pieretti M, Sutcliffe J S, Fu Y H, Kuhl D P A, et al. Cell. 1991;65:905–914. - PubMed

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