A Golgi study of neuronal architecture in a genetic mouse model for Lesch–Nyhan disease

Mikolaenko, Ivan; Rao, Lekha M.; Roberts, Rosalinda C.; Kolb, Bryan; Jinnah, Hyder A.

doi:10.1016/j.nbd.2005.04.005

Cited by 30 publications

(33 citation statements)

References 63 publications

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“…These mice exhibit metabolic abnormalities that are strikingly similar to abnormalities that have been reported for LND and its cell models, including loss of HPRT enzyme activity, failure of purine recycling, and accelerated synthesis of purines (Jinnah et al, 1992b;Jinnah et al, 1993). Studies of the brains of these mice demonstrate reduced dopamine along with microstructural anatomical abnormalities that are analogous to those demonstrated in the LND cell models (Jinnah et al, 1994;Jinnah et al, 1999b;Mikolaenko et al, 2005). These mice have been useful for demonstrating that HPRT deficiency leads to a loss of basal ganglia dopamine through a metabolic process rather than a degenerative one .…”

Section: Animal Models: Genes Lesions and Drugssupporting

confidence: 60%

Lesch-Nyhan disease: from mechanism to model and back again

Jinnah

2009

Disease Models &Amp; Mechanisms

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Lesch-Nyhan disease (LND) is a rare inherited disorder caused by mutations in the gene encoding hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by overproduction of uric acid, leading to gouty arthritis and nephrolithiasis. Affected patients also have characteristic neurological and behavioral anomalies. Multiple cell models have been developed to study the molecular and metabolic aspects of LND, and several animal models have been developed to elucidate the basis for the neurobehavioral syndrome. The models have different strengths and weaknesses rendering them suitable for studying different aspects of the disease. The extensive modeling efforts in LND have questioned the concept that an ‘ideal’ disease model is one that replicates all of its features because the pathogenesis of different elements of the disease involves different mechanisms. Instead, the modeling efforts have suggested a more fruitful approach that involves developing specific models, each tailored for addressing specific experimental questions.

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Section: Animal Models: Genes Lesions and Drugssupporting

confidence: 60%

Lesch-Nyhan disease: from mechanism to model and back again

Jinnah

2009

Disease Models &Amp; Mechanisms

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“…Hypoxanthine phosphoribosyltransferase mutations can lead to altered glial glutamate uptake (reviewed in Deutsch et al, 2005) and altered neuronal morphology (Mikolaenko et al, 2005). Perhaps ethanol-dependent reductions in HPRT1 expression cause similar effects.…”

Section: Discussionmentioning

confidence: 99%

Long‐Term Ethanol Self‐Administration by the Nonhuman Primate, Macaca fascicularis, Decreases the Benzodiazepine Sensitivity of Amygdala GABA_A Receptors

Anderson

Daunais

Friedman

et al. 2007

Alcoholism Clin & Exp Res

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Our findings demonstrate that chronic ethanol self-administration reduces the benzodiazepine sensitivity of amygdala GABA(A) receptors. This reduced sensitivity may be the result of decreased expression of an amygdala gamma subunit. These findings suggest that, while rodent and nonhuman primate models of chronic ethanol exposure share many characteristics, the specific molecular adaptations associated with the amygdala GABAergic system may not be identical.

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“…Each neuron was reconstructed by 3-dimensional digital tracing with NeuroLucida software (MicroBrightField, Williston VT) and a Wacom Intuos 2 digitizing tablet connected with an Olympus BX51 microscope and a 60x objective. Morphometric features of the cell soma and dendrites were determined by NeuroExplorer software version 10.21 as previously described (Mikolaenko et al, 2005; Song et al, 2013). Dendrite thicknesses, numbers and lengths were measured according to branch order.…”

Section: Methodsmentioning

confidence: 99%

Subtle microstructural changes of the cerebellum in a knock-in mouse model of DYT1 dystonia

Song¹,

Bernhard²,

Hess³

et al. 2014

Neurobiology of Disease

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The dystonias are a group of disorders characterized by involuntary twisting and repetitive movements. DYT1 dystonia is an inherited form of dystonia caused by a mutation in the TOR1A gene, which encodes torsinA. TorsinA is expressed in many regions of the nervous system, and the regions responsible for causing dystonic movements remain uncertain. Most prior studies have focused on the basal ganglia, although there is emerging evidence for abnormalities in the cerebellum too. In the current studies, we examined the cerebellum for structural abnormalities in a knock-in mouse model of DYT1 dystonia. The gross appearance of the cerebellum appeared normal in the mutant mice, but stereological measures revealed the cerebellum to be 5% larger in mutant compared to control mice. There were no changes in the numbers of Purkinje cells, granule cells, or neurons of the deep cerebellar nuclei. However, Golgi histochemical studies revealed Purkinje cells to have thinner dendrites, and fewer and less complex dendritic spines. There also was a higher frequency of heterotopic Purkinje cells displaced into the molecular layer. These results reveal subtle structural abnormalities of the cerebellum that are similar to those reported for the basal ganglia in the DYT1 knock-in mouse model.

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A Golgi study of neuronal architecture in a genetic mouse model for Lesch–Nyhan disease

Cited by 30 publications

References 63 publications

Lesch-Nyhan disease: from mechanism to model and back again

Lesch-Nyhan disease: from mechanism to model and back again

Long‐Term Ethanol Self‐Administration by the Nonhuman Primate, Macaca fascicularis, Decreases the Benzodiazepine Sensitivity of Amygdala GABA_A Receptors

Subtle microstructural changes of the cerebellum in a knock-in mouse model of DYT1 dystonia

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A Golgi study of neuronal architecture in a genetic mouse model for Lesch–Nyhan disease

Cited by 30 publications

References 63 publications

Lesch-Nyhan disease: from mechanism to model and back again

Lesch-Nyhan disease: from mechanism to model and back again

Long‐Term Ethanol Self‐Administration by the Nonhuman Primate, Macaca fascicularis, Decreases the Benzodiazepine Sensitivity of Amygdala GABAA Receptors

Subtle microstructural changes of the cerebellum in a knock-in mouse model of DYT1 dystonia

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Long‐Term Ethanol Self‐Administration by the Nonhuman Primate, Macaca fascicularis, Decreases the Benzodiazepine Sensitivity of Amygdala GABA_A Receptors