Abnormal cytoplasmic calcium dynamics in central neurons of a dystonia mouse model

Iwabuchi, Sadahiro; Kakazu, Yasuhiro; Koh, Joanna; Harata, Nobutoshi

doi:10.1016/j.neulet.2013.05.047

Cited by 20 publications

(20 citation statements)

References 42 publications

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“…Potential neuropathological and electrophysiological substrates of these findings are described in DYT1 heterozygous mice. These include subtle changes in cell size and synaptic structure in the striatum and cerebellum (Song et al, 2013), as well as abnormalities in synaptic vesicle recycling and calcium homeostasis (Iwabuchi, Kakazu, Koh, & Harata, 2013; Kakazu, Koh, Ho, et al, 2012; Kakazu, Koh, Iwabuchi, Gonzalez-Alegre, & Harata, 2012). …”

Section: Primary Dystoniamentioning

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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Section: Primary Dystoniamentioning

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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“…The labels remained clearly visible at 3 weeks ('3-week-old') and 32 weeks of age ('32-week-old'). The individual mice can be uniquely identified by a combination of tattoos on the four paws (numbers [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and by the information about the animal cage, or more complex numbering schemes (not shown).…”

Section: Tattooingmentioning

confidence: 99%

“…They were plated at low density on rat glial feeder layer that had been obtained from the CA3-CA1 region of hippocampus and seeded prior to neuronal plating, according to the scheme illustrated in Figure 7 (simplified summary of the procedures). Low-density cultures are optimal for the imaging of individual dendrites, somata 4,6 , nerve terminals 2,3,5,8 and axonal shafts 5 at high spatial resolution. The hippocampal cells (containing both neurons and glial cells) were plated on coated glass coverslips, either with ( Figure 8A) or without a pre-established glial feeder layer (Figure 8B, C) and observed with phase-contrast optics.…”

Section: Neuronal Culturesmentioning

confidence: 99%

“…The number of specimens can be scaled up (e.g., 96 samples) yet processed easily and simultaneously. Also the specimen type is not limited to tail clips; other sample types that could be used include ear punches, toe clippings, whole early embryos, and placenta tissues [2][3][4]29,30 . Different animal species can also be used.…”

Section: Genotypingmentioning

confidence: 99%

“…Here we demonstrate the working protocol that has been used for fast, simplified and reliable mouse genotyping in previous publications [2][3][4][5][6] . Mouse tails and a commercially available kit are used.…”

Section: Introductionmentioning

confidence: 98%

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Rapid Genotyping of Animals Followed by Establishing Primary Cultures of Brain Neurons

Koh

Iwabuchi

Huang

et al. 2015

JoVE

Self Cite

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High-resolution analysis of the morphology and function of mammalian neurons often requires the genotyping of individual animals followed by the analysis of primary cultures of neurons. We describe a set of procedures for: labeling newborn mice to be genotyped, rapid genotyping, and establishing low-density cultures of brain neurons from these mice. Individual mice are labeled by tattooing, which allows for long-term identification lasting into adulthood. Genotyping by the described protocol is fast and efficient, and allows for automated extraction of nucleic acid with good reliability. This is useful under circumstances where sufficient time for conventional genotyping is not available, e.g., in mice that suffer from neonatal lethality. Primary neuronal cultures are generated at low density, which enables imaging experiments at high spatial resolution. This culture method requires the preparation of glial feeder layers prior to neuronal plating. The protocol is applied in its entirety to a mouse model of the movement disorder DYT1 dystonia (ΔE-torsinA knock-in mice), and neuronal cultures are prepared from the hippocampus, cerebral cortex and striatum of these mice. This protocol can be applied to mice with other genetic mutations, as well as to animals of other species. Furthermore, individual components of the protocol can be used for isolated sub-projects. Thus this protocol will have wide applications, not only in neuroscience but also in other fields of biological and medical sciences. Video LinkThe video component of this article can be found at

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Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High‐Throughput Sequencing

2016

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Dystonia is a genetically heterogenous disease and a prototype disorder where next-generation sequencing has facilitated the identification of new pathogenic genes. This includes the first two genes linked to recessively inherited isolated dystonia, that is, HPCA (hippocalcin) and COL6A3 (collagen VI alpha 3). These genes are proposed to underlie cases of the so-called DYT2-like dystonia, while also reiterating two distinct pathways in dystonia pathogenesis. First, deficiency in HPCA function is thought to alter calcium homeostasis, a mechanism that has previously been forwarded for CACNA1A and ANO3. The novel myoclonus-dystonia genes KCTD17 and CACNA1B also implicate abnormal calcium signaling in dystonia. Second, the phenotype in COL6A3-loss-of-function zebrafish models argues for a neurodevelopmental defect, which has previously been suggested as a possible biological mechanism for THAP1, TOR1A, and TAF1 based on expression data. The newly reported myoclonus-dystonia gene, RELN, plays also a role in the formation of brain structures. Defects in neurodevelopment likewise seem to be a recurrent scheme underpinning mainly complex dystonias, for example those attributable to biallelic mutations in GCH1, TH, SPR, or to heterozygous TUBB4A mutations. To date, it remains unclear whether dystonia is a common phenotypic outcome of diverse underlying disease mechanisms, or whether the different genetic causes converge in a single pathway. Importantly, the relevance of pathways highlighted by novel dystonia genes identified by high-throughput sequencing depends on the confirmation of mutation pathogenicity in subsequent genetic and functional studies. However, independent, careful validation of genetic findings lags behind publications of newly identified genes. We conclude with a discussion on the characteristics of true-positive reports.

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Abnormal cytoplasmic calcium dynamics in central neurons of a dystonia mouse model

Cited by 20 publications

References 42 publications

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

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

Rapid Genotyping of Animals Followed by Establishing Primary Cultures of Brain Neurons

Novel Dystonia Genes: Clues on Disease Mechanisms and the Complexities of High‐Throughput Sequencing

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