Quantitative magnetic resonance imaging in Rett syndrome

Naidu, Sakkubai; Goldberg, T.E.; Moser, Hugo W.; Khoromi, Suzan; Kumar, Anand; Je, Kleinman; Weinberger, D.R.

doi:10.1176/jnp.3.1.66

Cited by 28 publications

(8 citation statements)

References 62 publications

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“…Additionally, it has long been known that RTT females display microcephaly on a gross anatomic scale, with brain volume generally being reduced by 25% (57–59). …”

Section: Discussionmentioning

confidence: 99%

MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats

et al. 2016

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Since the identification of MECP2 as the causative gene in the majority of Rett Syndrome (RTT) cases, transgenic mouse models have played a critical role in our understanding of this disease. The use of additional mammalian RTT models offers the promise of further elucidating critical early mechanisms of disease as well as providing new avenues for translational studies. We have identified significant abnormalities in growth as well as motor and behavioural function in a novel zinc-finger nuclease model of RTT utilizing both male and female rats throughout development. Male rats lacking MeCP2 (Mecp2ZFN/y) were noticeably symptomatic as early as postnatal day 21, with most dying by postnatal day 55, while females lacking one copy of Mecp2 (Mecp2ZFN/+) displayed a more protracted disease course. Brain weights of Mecp2ZFN/y and Mecp2ZFN/+ rats were significantly reduced by postnatal day 14 and 21, respectively. Early motor and breathing abnormalities were apparent in Mecp2ZFN/y rats, whereas Mecp2ZFN/+ rats displayed functional irregularities later in development. The large size of this species will provide profound advantages in the identification of early disease mechanisms and the development of appropriately timed therapeutics. The current study establishes a foundational basis for the continued utilization of this rat model in future RTT research.

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“…Additionally, it has long been known that RTT females display microcephaly on a gross anatomic scale, with brain volume generally being reduced by 25% (57–59). …”

Section: Discussionmentioning

confidence: 99%

MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats

et al. 2016

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“…Imaging studies of RTT subjects demonstrate decreased cerebral volumes (Carter et al, 2008; Jellinger, 2003; Murakami, Courchesne, Haas, Press, & Yeung-Courchesne, 1992), with reductions in caudate nucleus, cortical, and midbrain volumes disproportionately reduced compared to other structures (Casanova et al, 1991; Dunn et al, 2002; Reiss et al, 1993; Subramaniam, Naidu, & Reiss, 1997). PET imaging studies demonstrate specific changes in BG transmitter function.…”

Section: Diseases and Links To Striatal Dysfunctionmentioning

confidence: 99%

Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

Pappas

Leventhal

Albin

et al. 2014

Current Topics in Developmental Biology

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This chapter focuses on neurodevelopmental diseases that are tightly linked to abnormal function of the striatum and connected structures. We begin with an overview of three representative diseases in which striatal dysfunction plays a key role—Tourette syndrome and obsessive-compulsive disorder, Rett's syndrome, and primary dystonia. These diseases highlight distinct etiologies that disrupt striatal integrity and function during development, and showcase the varied clinical manifestations of striatal dysfunction. We then review striatal organization and function, including evidence for striatal roles in online motor control/action selection, reinforcement learning, habit formation, and action sequencing. A key barrier to progress has been the relative lack of animal models of these diseases, though recently there has been considerable progress. We review these efforts, including their relative merits providing insight into disease pathogenesis, disease symptomatology, and basal ganglia function.

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“…As regards cortical WM, mild and diffuse reductions have been previously reported and linked to axonal pathology (50). Notably, studies in this field have selectively shown decreased volumes of the cerebrum, cerebellum, and caudate nucleus (43,44,(50)(51)(52)(53). Surface-based morphological approaches, including cortical gyrification and regional cortical thickness evaluation, have not been fully explored.…”

Section: Morphologic Mri In Rtt With Mecp2 Mutationmentioning

confidence: 99%

Multimodal Neuroimaging in Rett Syndrome With MECP2 Mutation

Zhao-hong

et al. 2022

Front. Neurol.

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Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up-to date neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET–MRI approaches are urgently needed to further explore RTT brain alterations.

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Quantitative magnetic resonance imaging in Rett syndrome

Cited by 28 publications

References 62 publications

MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats

MeCP2 deficiency results in robust Rett-like behavioural and motor deficits in male and female rats

Mouse Models of Neurodevelopmental Disease of the Basal Ganglia and Associated Circuits

Multimodal Neuroimaging in Rett Syndrome With MECP2 Mutation

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