An in vivo and in vitro 1H-magnetic resonance spectroscopy study of mdx mouse brain: Abnormal development or neural necrosis?

Tracey, Irene; Dunn, Jeff F.; Parkes, Harold G.; Radda, George K.

doi:10.1016/0022-510x(96)00135-9

Cited by 35 publications

(30 citation statements)

References 38 publications

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“…Elevated concentrations of choline-containing compounds has previously been reported in extracts of whole brain (60–150 days old) [22] and in the HP and CB (> 6 months old) in mdx mice [65]. More specifically, our current in vivo study demonstrated an elevated concentration of PCh in HP.…”

Section: Discussionsupporting

confidence: 76%

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Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Shi

Pratt

et al. 2015

Neuromuscular Disorders

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Duchenne muscular dystrophy (DMD), an X-linked disorder caused by the lack of dystrophin, is characterized by the progressive wasting of skeletal muscles. To date, what is known about dystrophin function is derived from studies of dystrophin-deficient animals, with the most common model being the mdx mouse. Most studies on patients with DMD and in mdx mice have focused on skeletal muscle and the development of therapies to reverse, or at least slow, the severe muscle wasting and progressive degeneration. However, dystrophin is also expressed in the CNS. Both mdx mice and patients with DMD can have cognitive and behavioral changes, but studies in the dystrophic brain are limited. We examined the brain structure and metabolites of mature wild type (WT) and mdx mice using magnetic resonance imaging and spectroscopy (MRI/MRS). Both structural and metabolic alterations were observed in the mdx brain. Enlarged lateral ventricles were detected in mdx mice when compared to WT. Diffusion tensor imaging revealed elevations in diffusion diffusivities in the prefrontal cortex and a reduction of fractional anisotropy in the hippocampus. Metabolic changes included elevations in phosphocholine and glutathione, and a reduction in γ-aminobutyric acid in the hippocampus. In addition, an elevation in taurine was observed in the prefrontal cortex. Such findings indicate a regional structural change, altered cellular antioxidant defenses, a dysfunction of GABAergic neurotransmission, and a perturbed osmoregulation in the brain lacking dystrophin.

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Section: Discussionsupporting

confidence: 76%

“…Very few studies have explored in vivo 1 H MRS on mdx mice. In an early non-localized in vivo 1 H MRS study, there were significantly low ratios of Cr/tCho and NAA/tCho in mdx brains compared to controls at the age between 2 and 5 months [22]. …”

Section: Introductionmentioning

confidence: 99%

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Shi

Pratt

et al. 2015

Neuromuscular Disorders

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“…Creatine, taurine, and choline-containing metabolites have been reported to be altered in concentration in dystrophic tissue in previous studies in muscle (9,20) and brain (10,12,13,21). However, these studies investigated only a small number of metabolites and often in only one tissue type.…”

Section: Discussionmentioning

confidence: 89%

Metabolic Profiling of Genetic Disorders: A Multitissue 1H Nuclear Magnetic Resonance Spectroscopic and Pattern Recognition Study into Dystrophic Tissue

Griffin

Williams

Sang

et al. 2001

Analytical Biochemistry

142

102

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“…A number of studies in mice and humans have found a correlation between astrocytosis and elevated C/C ratios (37)(38)(39)(40). Genetic disorders of astrocytes associated pathologically with astrocytosis displayed increased C/C ratios on MRS (38).…”

Section: Discussionmentioning

confidence: 99%

Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior

Gantois

Fang

Jiang

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Huntington's disease is characterized by death of striatal projection neurons. We used a Cre/Lox transgenic approach to generate an animal model in which D1 dopamine receptor (Drd1a)؉ cells are progressively ablated in the postnatal brain. Striatal Drd1a, substance P, and dynorphin expression is progressively lost, whereas D2 dopamine receptor (Drd2) and enkephalin expression is up-regulated. Magnetic resonance spectroscopic analysis demonstrated early elevation of the striatal choline/creatine ratio, a finding associated with extensive reactive striatal astrogliosis. Sequential MRI demonstrated a progressive reduction in striatal volume and secondary ventricular enlargement confirmed to be due to loss of striatal cells. Mutant mice had normal gait and rotarod performance but displayed hindlimb dystonia, locomotor hyperactivity, and handling-induced electrographically verified spontaneous seizures. Ethological assessment identified an increase in rearing and impairments in the oral behaviors of sifting and chewing. In line with the limbic seizure profile, cell loss, astrogliosis, microgliosis, and down-regulated dynorphin expression were seen in the hippocampal dentate gyrus. This study specifically implicates Drd1a؉ cell loss with tail suspension hindlimb dystonia, hyperactivity, and abnormal oral function. The latter may relate to the speech and swallowing disturbances and the classic sign of tongueprotrusion motor impersistence observed in Huntington's disease. In addition, the findings of this study support the notion that Drd1a and Drd2 are segregated on striatal projection neurons. striatum ͉ Cre ͉ Huntington's disease T he nigrostriatal pathway projects from the midbrain substantia nigra pars compacta to innervate the dorsal striatum. Dopamine is released from dopaminergic terminals in the striatum to regulate motor activity and eating behavior (1). Early studies suggested that dopamine D1 (Drd1a) and D2 receptors (Drd2) are segregated on striatal projection neurons; the Drd1a is expressed on substance P and dynorphin-positive striatal neurons, which project directly to the substantia nigra pars reticulata/entopeduncular complex (known as the direct pathway), whereas Drd2 is preferentially expressed on enkephalin-positive striatopallidal projecting neurons (2). Neurons within the globus pallidus then project to the subthalamic nucleus, which in turn relays to the substantia nigra pars reticulata/entopeduncular complex (known as the indirect pathway). Dopamine also modulates the activity of glutamatergic corticostriatal input on striatal projection neurons.Idiopathic Parkinson's disease is characterized by the death of dopaminergic neurons; however, rare Parkinsonian syndromes have been identified in which the defect is associated with cell death in the dopamine-responsive neurons in the striatum (3-6). Huntington's disease (HD) (7-10), a neurodegenerative condition with motor, cognitive, and psychiatric disturbances, also involves death of dopamine receptor-expressing striatal projection neurons. Several ...

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An in vivo and in vitro 1H-magnetic resonance spectroscopy study of mdx mouse brain: Abnormal development or neural necrosis?

Cited by 35 publications

References 38 publications

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Abnormalities in brain structure and biochemistry associated with mdx mice measured by in vivo MRI and high resolution localized 1H MRS

Metabolic Profiling of Genetic Disorders: A Multitissue 1H Nuclear Magnetic Resonance Spectroscopic and Pattern Recognition Study into Dystrophic Tissue

Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior

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