Dataset Information

Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles.

ABSTRACT: Ventricular enlargement (VE) is commonly observed in aging and fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. VE may generate a mechanical force causing structural deformation. In this longitudinal study, we examined the relationships between VE and structural changes in the corpus callosum (CC) and putamen. MRI scans (2-7/person over 0.2-7.5 years) were acquired from 22 healthy controls, 26 unaffected premutation carriers (PFX-), and 39 carriers affected with FXTAS (PFX+). Compared with controls, PFX- demonstrated enlarged fourth ventricles, whereas PFX+ displayed enlargement in both third and fourth ventricles, CC thinning, putamen atrophy/deformation (thinning and increased distance), and accelerated expansions in lateral ventricles. Common for all groups, baseline VE predicted accelerated CC thinning and putamen atrophy/deformation and conversely, baseline CC and putamen atrophy/deformation and enlarged third and fourth ventricles predicted accelerated lateral ventricular expansion. The results suggest a progressive VE within the 4 ventricles as FXTAS develops and a deleterious cycle between VE and brain deformation that may commonly occur during aging and FXTAS progression but become accelerated in FXTAS.

SUBMITTER: Wang JY

PROVIDER: S-EPMC6995416 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles.

Wang Jun Yi JY Hessl David D Tassone Flora F Kim Kyoungmi K Hagerman Randi J RJ Rivera Susan M SM

Neurobiology of aging 20190924

Ventricular enlargement (VE) is commonly observed in aging and fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. VE may generate a mechanical force causing structural deformation. In this longitudinal study, we examined the relationships between VE and structural changes in the corpus callosum (CC) and putamen. MRI scans (2-7/person over 0.2-7.5 years) were acquired from 22 healthy controls, 26 unaffected premutation carriers (PFX-), and 39 carriers af ...[more]

PMID: 31733943

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Project description:Individuals with the fragile X premutation express expanded CGG repeats (repeats 55-200) in the FMR1 gene and elevated FMR1 messenger RNA (mRNA) levels, both of which may underlie the occurrence of the late-onset neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Because the core feature of FXTAS is motor impairment, determining the influence of FMR1 mRNA levels on structural connectivity of motor fiber tracts is critical for a better understanding of the pathologic features of FXTAS.To examine the associations of CGG repeat and FMR1 mRNA with motor-related fiber tracts in males with premutation alleles.A case-control study conducted at the University of California, Davis, from April 1, 2008, through August 31, 2009. All data were collected masked to the carrier status of the FMR1 gene.Thirty-six male premutation carriers with FXTAS and 26 male premutation carriers without FXTAS were recruited through their family relationships with children affected by fragile X syndrome. The controls were 34 unaffected family members and healthy volunteers from the local community.The CGG repeat lengths and FMR1 mRNA expression levels in peripheral blood lymphocytes, motor functioning, and white matter structural integrity that were estimated using diffusion tensor imaging. After data collection, we selected 4 motor tracts to reconstruct using diffusion tensor tractography, namely, the middle and superior cerebellar peduncles, descending motor tracts (containing the corticospinal, corticobulbar, and corticopontine tracts), and the anterior body of the corpus callosum.All fiber tracts exhibited weaker structural connectivity in the FXTAS group (decreased 5%-53% from controls, P ? .02). Genetic imaging correlation analysis revealed negative associations of CGG repeat length and FMR1 mRNA with connectivity strength of the superior cerebellar peduncles in both premutation groups (partial r² = 0.23-0.33, P ? .004). In addition, the measurements from the corpus callosum and superior cerebellar peduncles revealed a high correlation with motor functioning in all 3 groups (r between partial least square predicted and actual test scores = 0.41-0.56, P ? .04).Distinct pathophysiologic processes may underlie the structural impairment of the motor tracts in FXTAS. Although both the corpus callosum and superior cerebellar peduncles were of great importance to motor functioning, only the superior cerebellar peduncles exhibited an association with the elevated RNA levels in the blood of fragile X premutation carriers.

Dataset Information

Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles.

Publications

Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles.

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