Endogenous neural precursors influence grafted neural stem cells and contribute to neuroprotection in the parkinsonian rat

Lalitha Madhavan, Brian F. Daley, Caryl E. Sortwell, Timothy J. Collier

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Neuroprotective and neurorescue effects after neural stem/precursor cell (NPC) transplantation have been reported, but the mechanisms underlying such phenomena are not well understood. Our recent findings in a rat Parkinson's disease (PD) model indicate that transplantation of NPCs before a 6-hydroxydopamine (6-OHDA) insult can result in nigrostriatal protection which is associated with endogenous NPC proliferation, migration and neurogenesis. Here, we sought to determine whether the observed endogenous NPC response (i) contributes to transplanted NPC-mediated neuroprotection; and/or (ii) affects graft phenotype and function. Host Fischer 344 rats were administered the antimitotic agent cytosine-β-d-arabinofuranoside (Ara-C) to eliminate actively proliferating endogenous neural precursors before being transplanted with NPCs and treated with 6-OHDA to induce nigrostriatal degeneration. Behavioral and histological analyses demonstrate that the neuroprotective response observed in NPC transplanted animals which had not received Ara-C was significantly attenuated in animals which did receive pre-transplant Ara-C. Also, while grafts in Ara-C-treated animals showed no decrease in cell number, they exhibited significantly reduced expression of the neural stem cell regulators nestin and sonic hedgehog. In addition, inhibition of the endogenous NPC response resulted in an exaggerated host glial reaction. Overall, the study establishes for the first time that endogenous NPCs contribute to transplanted NPC-mediated therapeutic effects by affecting both grafted and mature host cells in unique ways. Thus, both endogenous and transplanted NPCs are important in creating an environment suitable for neural protection and rescue, and harnessing their synergistic interaction may lead to the optimization of cell-based therapies for PD.

Original languageEnglish (US)
Pages (from-to)883-895
Number of pages13
JournalEuropean Journal of Neuroscience
Volume35
Issue number6
DOIs
StatePublished - Mar 2012

Fingerprint

Neural Stem Cells
Cytarabine
Oxidopamine
Transplants
Parkinson Disease
Antimitotic Agents
Nestin
Hedgehogs
Neuroprotection
Cytosine
Neurogenesis
Inbred F344 Rats
Stem Cell Transplantation
Neuroprotective Agents
Therapeutic Uses
Cell- and Tissue-Based Therapy
Neuroglia
Cell Movement
Cell Count
Transplantation

Keywords

  • Neural precursor cells
  • Neurogenesis
  • Parkinson's disease
  • Subventricular zone
  • Transplantation

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Endogenous neural precursors influence grafted neural stem cells and contribute to neuroprotection in the parkinsonian rat. / Madhavan, Lalitha; Daley, Brian F.; Sortwell, Caryl E.; Collier, Timothy J.

In: European Journal of Neuroscience, Vol. 35, No. 6, 03.2012, p. 883-895.

Research output: Contribution to journalArticle

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