Target-specific forebrain projections and appropriate synaptic inputs of hESC-derived dopamine neurons grafted to the midbrain of parkinsonian rats

The Journal of Comparative Neurology
Tiago CardosoMalin Parmar

Abstract

Dopamine (DA) neurons derived from human embryonic stem cells (hESCs) are a promising unlimited source of cells for cell replacement therapy in Parkinson's disease (PD). A number of studies have demonstrated functionality of DA neurons originating from hESCs when grafted to the striatum of rodent and non-human primate models of PD. However, several questions remain in regard to their axonal outgrowth potential and capacity to integrate into host circuitry. Here, ventral midbrain (VM) patterned hESC-derived progenitors were grafted into the midbrain of 6-hydroxydopamine-lesioned rats, and analyzed at 6, 18, and 24 weeks for a time-course evaluation of specificity and extent of graft-derived fiber outgrowth as well as potential for functional recovery. To investigate synaptic integration of the transplanted cells, we used rabies-based monosynaptic tracing to reveal the origin and extent of host presynaptic inputs to grafts at 6 weeks. The results reveal the capacity of grafted neurons to extend axonal projections toward appropriate forebrain target structures progressively over 24 weeks. The timing and extent of graft-derived dopaminergic fibers innervating the dorsolateral striatum matched reduction in amphetamine-induced rotati...Continue Reading

References

Oct 1, 1992·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J C Adams
Nov 5, 1997·Nature Biotechnology·R ZuffereyD Trono
Aug 14, 2009·The European Journal of Neuroscience·Lachlan H ThompsonAnders Björklund
Jul 2, 2010·Science Translational Medicine·Marios PolitisPaola Piccini
Jun 12, 2012·Neuron·Mitsuko Watabe-UchidaNaoshige Uchida
Nov 13, 2013·JAMA Neurology·Zinovia KefalopoulouThomas Foltynie
Jun 13, 2014·Nature·Alison Abbott
Apr 10, 2015·Neuron·Julius A Steinbeck, Lorenz Studer
Aug 5, 2015·Nature Reviews. Neurology·Roger A BarkerMalin Parmar
May 4, 2016·Proceedings of the National Academy of Sciences of the United States of America·Wen LiJia-Yi Li
Sep 1, 2017·Nature Communications·Asuka MorizaneJun Takahashi

❮ Previous
Next ❯

Citations

Jan 19, 2019·The European Journal of Neuroscience·Beatrice WeykopfOliver Brüstle
Dec 6, 2019·International Journal of Molecular Sciences·Julia KonovalovaAndrii Domanskyi
Jan 8, 2020·Nature Reviews. Neuroscience·Malin ParmarClaire Henchcliffe
Feb 13, 2020·Current Protocols in Neuroscience·Mikko AiravaaraAndrii Domanskyi
Jan 15, 2020·NPJ Parkinson's Disease·James P HarrisD Kacy Cullen
Jun 18, 2020·Frontiers in Cellular Neuroscience·Anders Björklund, Malin Parmar
Dec 6, 2019·Frontiers in Neuroscience·Daniel HenriquesLiliana S Mendonça
Jul 7, 2020·Frontiers in Cell and Developmental Biology·Tiago Cardoso, Martin Lévesque
Sep 10, 2020·Frontiers in Cell and Developmental Biology·Tae Wan KimLorenz Studer
Jun 11, 2020·Nature Reviews. Neuroscience·Itzhak FischerMichael A Lane
Jun 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Deirdre B HobanMalin Parmar
Nov 1, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Philip C Buttery, Roger A Barker
Sep 24, 2020·Cell Stem Cell·Man XiongSu-Chun Zhang
Dec 20, 2020·International Journal of Molecular Sciences·You Jung KangHansang Cho
Jan 8, 2021·NPJ Parkinson's Disease·James P HarrisD Kacy Cullen
Apr 6, 2021·Journal of Parkinson's Disease·Anders Björklund, Malin Parmar
May 14, 2021·Current Opinion in Neurobiology·Magdalena Götz, Riccardo Bocchi
Jul 13, 2021·Journal of Parkinson's Disease·Mark Tomishima, Agnete Kirkeby
Aug 1, 2021·Brain Research Bulletin·Wisberty J Gordián-VélezD Kacy Cullen

❮ Previous
Next ❯

Software Mentioned

Cinema
ImageJ ( FIJI
Cinema 4D

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.