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• W2135864962 abstract "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 tongue-protrusion 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." @default.
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• W2135864962 date "2007-03-06" @default.
• W2135864962 modified "2023-10-15" @default.
• W2135864962 title "Ablation of D1 dopamine receptor-expressing cells generates mice with seizures, dystonia, hyperactivity, and impaired oral behavior" @default.
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• W2135864962 doi "https://doi.org/10.1073/pnas.0611625104" @default.
• W2135864962 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1820729" @default.
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• W2135864962 hasPublicationYear "2007" @default.
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