6-OHDA model and first rat dopamine grafts

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Urban Ungerstedt (Karolinska, 1968 onwards; with Gordon Arbuthnott for the 1970 rotation assay). Perlow, Freed, Hoffer, Seiger, Olson and Wyatt (Science 1979; affiliations not confirmed). Anders Björklund and Ulf Stenevi (Lund, Brain Research 1979).

What happened

Ungerstedt's 1968 paper showed that 6-hydroxydopamine (6-OHDA) destroys central monoamine neurons. Ungerstedt and Arbuthnott (Brain Res 1970) then used one-sided 6-OHDA lesions of the nigrostriatal pathway in rats and a rotation count to measure the lesion's effect, the basis of the standard rat model of dopamine-neuron loss. In 1979 two groups grafted fetal dopamine neurons into lesioned rats. Perlow et al. placed the cells next to the caudate; the grafts survived, sent out axons and significantly reduced the lesion-induced motor abnormalities. Björklund & Stenevi grafted embryonic nigral tissue into the parietal cortex of adult rats, where it established a new dopamine input to the denervated neostriatum (the part of the abstract I could read stops there; I did not confirm a motor benefit in this paper).

Why it moved us toward a cure

Together these gave the first reproducible lesion model and the first demonstration that replacing the lost cells can repair the circuit. That is the conceptual root of the fetal (landmark 3) and stem-cell (landmarks 17, 10) trials.

Outcome

Advanced. 6-OHDA is still a workhorse model, and cell replacement led to the 2025 trials.

Sources

• Ungerstedt U, "6-Hydroxy-dopamine induced degeneration of central monoamine neurons", Eur J Pharmacol 1968;5:107-110, DOI 10.1016/0014-2999(68)90164-7, PMID 5718510 (citation only)
• Ungerstedt & Arbuthnott, "Quantitative recording of rotational behavior in rats after 6-hydroxy-dopamine lesions of the nigrostriatal dopamine system", Brain Res 1970;24:485-493, DOI 10.1016/0006-8993(70)90187-3, PMID 5494536 (title only)
• Perlow MJ, Freed WJ, Hoffer BJ, Seiger A, Olson L, Wyatt RJ, "Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system", Science 1979;204:643–647, DOI 10.1126/science.571147, PMID 571147 (abstract read via PubMed)
• Björklund A & Stenevi U, "Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants", Brain Res 1979;177:555–560, DOI 10.1016/0006-8993(79)90472-4, PMID 574053 (partial abstract via a Lund-hosted PDF, this record)
• Lund University history of cell therapy for Parkinson's
• Not yet verified: the authors' affiliations on both 1979 papers (PubMed lists none; NIH and Karolinska for Perlow et al. is carried over from the earlier draft); whether Björklund & Stenevi reported a motor benefit; exact graft numbers; the full texts.