Localization of dopamine receptors and associated mRNA in transplants of human fetal striatal tissue in rodents with experimental Huntington's Disease

Pundt, Lisa L.; Narang, Neelam; Kondoh, Takeshi; Low, Walter C.

doi:10.1016/s0168-0102(96)01163-7

Cited by 12 publications

(6 citation statements)

References 70 publications

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“…A higher dosage of DA was required to suppress striatal neurons in the lesioned animals, suggesting that the sensitivity to DA was decreased after QA lesioning. It has been reported that animals and patients with HD have low levels of D1 and D2 receptors [1,11,17,22]. The decrease in electrophysiological sensitivity to DA may be secondary to the loss of DA receptors in the striatum.…”

Section: Discussionmentioning

confidence: 99%

“…Binding of [ 3 H]SCH23390 and [ 3 H]sulpride to D1 and D2 receptors can be reduced by QA treatment [16]. The reduction of D1 and D2 receptors correlates well with the severity of HD [17,22]. The downregulation of DA receptors results in the attenuation of DA receptormediated responses in lesioned animals.…”

Section: Introductionmentioning

confidence: 99%

“…Histochemical analysis has indicated that these grafts contain GABA, substance P, acetylcholinesterase-positive cell bodies [29] and tyrosine hydroxylase (TH)-positive fibers [6,24]. The transplants also possess many D1 receptors [11] and high levels of expression of D2 receptor mRNA [22]. It is possible that the expression of these DA receptors in the graft may restore DA transmission in animals with HD.…”

Section: Introductionmentioning

confidence: 99%

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Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington’s Disease

Chen¹,

Jeng²,

Lin³

et al. 2002

J Biomed Sci

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Dopamine (DA), a major neurotransmitter used in the striatum, is involved in movement disorders such as Parkinson’s disease and Huntington’s chorea. With the loss of neurons in the striatum of patients with Huntington’s disease (HD), there is an associated downregulation of DA receptors, which may alter DA-mediated responses. In the present study, DA-mediated electrophysiological depression was studied in animals with quinolinic acid (QA)-induced experimental HD. QA was directly applied to the right striatum of adult female Sprague-Dawley rats. Animals receiving QA developed ipsilateral rotation after the application of apomorphine. Fetal striatal tissue transplants grafted 1 month after lesioning attenuated apomorphine-induced rotation. Six months after lesioning, the animals were anesthetized with urethane for electrophysiological study. DA, applied directly to neurons by pressure microejection, inhibited spontaneous single-unit activity in the striatal neurons of nonlesioned, lesioned and lesioned/grafted rats. QA lesioning reduced responses to DA in the striatal neurons. The dose of DA required to inhibit striatal neuron activity in the lesioned rats was significantly increased compared to that in the nonlesioned rats. Transplantation of fetal striatal tissue restored the electrophysiological sensitivity to DA in the lesioned striatum. The dose of DA used to suppress striatal neuron activity was reduced after grafting. Immunohistostaining showed survival of γ-aminobutyric acid neurons at the graft site. Tyrosine hydroxylase-positive terminals were found innervating the striatal grafts. In conclusion, our data demonstrate that fetal striatal transplants restore electrophysiological sensitivity to DA in the lesioned striatum of animals with experimental HD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington’s Disease

Chen¹,

Jeng²,

Lin³

et al. 2002

J Biomed Sci

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“…Transplantation of fetal tissue into HD patients has been seen as a relative success in clinical trials . Preclinical data suggested that tissue derived from the human fetal ganglionic eminences could engraft into the STR in the quinolinic acid lesion model of HD, survive up to 9 months post‐transplantation, and ameliorate apomorphine‐induced rotational deficits . Primary fetal grafts from 6 to 11 postgestational week ganglionic eminences, still containing dividing cells, resulted in differentiation toward immature neurons and few region‐specific mature neurons .…”

Section: Human–animal Chimerismmentioning

confidence: 99%

Concise Review: Human-Animal Neurological Chimeras: Humanized Animals or Human Cells in an Animal?

et al. 2019

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Blastocyst complementation is an emerging methodology in which human stem cells are transferred into genetically engineered preimplantation animal embryos eventually giving rise to fully developed human tissues and organs within the animal host for use in regenerative medicine. The ethical issues surrounding this method have caused the National Institutes of Health to issue a moratorium on funding for blastocyst complementation citing the potential for human cells to substantially contribute to the brain of the chimeric animal. To address this concern, we performed an in-depth review of the neural transplantation literature to determine how the integration of human cells into the nonhuman neural circuitry has altered the behavior of the host. Despite reports of widespread integration of human cell transplants, our review of 150 transplantation studies found no evidence suggestive of humanization of the animal host, and we thus conclude that, at present, concerns over humanization should not prevent research on blastocyst complementation to continue. We suggest proceeding in a controlled and transparent manner, however, and include recommendations for future research with careful consideration for how human cells may contribute to the animal host nervous system. STEM CELLS 2019;37:444-452 SIGNIFICANCE STATEMENTDue to a severe shortage of human organs and tissues, thousands of patients die each year due to an inability to procure organs for transplantation. Blastocyst complementation is a methodology that has the potential to generate large quantities of functioning human organs and tissues but is hindered by a National Institutes of Health moratorium on funding, citing concern over substantial human cell contribution to the brain of the animal. This review summarizes published, peer-reviewed studies on human-animal neural transplantation and suggests that this concern over neurological chimerism should not prevent research to continue in a controlled and transparent manner.

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“…Histochemical analysis has indicated that these grafts contain GABA, substance P, acetylcholinesterase-positive cell bodies [29] and tyrosine hydmxylase (TH)-positive fibers [6,24]. The transplants also possess many D 1 receptors [11] and high levels of expression of D2 receptor mRNA [22]. It is possible that the expression of these DA receptors in the graft may restore IDA transmission in animals with HD.…”

Section: Introductionmentioning

confidence: 99%

Fetal striatal transplants restore electrophysiological sensitivity to dopamine in the lesioned striatum of rats with experimental Huntington's disease

et al. 2002

View full text Add to dashboard Cite

Dopamine (DA), a major neurotransmitter used in the striatum, is involved in movement disorders such as Parkinson's disease and Huntington's chorea. With the loss of neurons in the striatum of patients with Huntington's disease (HD), there is an associated downregulation of DA receptors, which may alter DA-mediated responses. In the present study, DA-mediated electrophysiological depression was studied in animals with quinolinic acid (QA)-induced experimental HD. QA was directly applied to the right striatum of adult female Sprague-Dawley rats. Animals receiving QA developed ipsilateral rotation after the application of apomorphine. Fetal striatal tissue transplants grafted 1 month after lesioning attenuated apomorphine-induced rotation. Six months after lesioning, the animals were anesthetized with urethane for electrophysiological study. DA, applied directly to neurons by pressure microejection, inhibited spontaneous single-unit activity in the striatal neurons of nonlesioned, lesioned and lesioned/grafted rats. QA lesioning reduced responses to DA in the striatal neurons. The dose of DA required to inhibit striatal neuron activity in the lesioned rats was significantly increased compared to that in the nonlesioned rats. Transplantation of fetal striatal tissue restored the electrophysiological sensitivity to DA in the lesioned striatum. The dose of DA used to suppress striatal neuron activity was reduced after grafting. Immunohistostaining showed survival of gamma-aminobutyric acid neurons at the graft site. Tyrosine hydroxylase-positive terminals were found innervating the striatal grafts. In conclusion, our data demonstrate that fetal striatal transplants restore electrophysiological sensitivity to DA in the lesioned striatum of animals with experimental HD.

show abstract

Localization of dopamine receptors and associated mRNA in transplants of human fetal striatal tissue in rodents with experimental Huntington's Disease

Cited by 12 publications

References 70 publications

Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington’s Disease

Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington’s Disease

Concise Review: Human-Animal Neurological Chimeras: Humanized Animals or Human Cells in an Animal?

Fetal striatal transplants restore electrophysiological sensitivity to dopamine in the lesioned striatum of rats with experimental Huntington's disease

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Localization of dopamine receptors and associated mRNA in transplants of human fetal striatal tissue in rodents with experimental Huntington's Disease

Cited by 12 publications

References 70 publications

Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington&rsquo;s Disease

Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington&rsquo;s Disease

Concise Review: Human-Animal Neurological Chimeras: Humanized Animals or Human Cells in an Animal?

Fetal striatal transplants restore electrophysiological sensitivity to dopamine in the lesioned striatum of rats with experimental Huntington's disease

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Resources

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Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington’s Disease

Fetal Striatal Transplants Restore Electrophysiological Sensitivity to Dopamine in the Lesioned Striatum of Rats with Experimental Huntington’s Disease