Landmark 343 · Discovery
Calbindin dopamine neurons spared
In short
Two post-mortem studies found that midbrain dopamine neurons containing the calcium-binding protein calbindin were relatively spared, and that the neighbouring ventral tegmental area lost fewer cells than the nigra, giving the first molecular clue to why some dopamine cells survive.
- What it is
- Discovery
- Outcome
- Still being studied
- When
- 1990–1992
- Approach
- Keep vulnerable cells alive
- Research lane
- Selective vulnerability
- Last checked
- 19 Oct 2026
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
Toshiko Yamada, Patrick McGeer, Kenneth Baimbridge and Edith McGeer (Kinsmen Laboratory, University of British Columbia, Vancouver, 1990); Dwight German, Kalynn Manaye, Patricia Sonsalla and Beth Brooks (German's group at UT Southwestern Medical Center, Dallas, 1992). Funders are not stated in the abstracts.
What happened
Dopamine neurons in the substantia nigra die in Parkinson's (landmark 21). Next door, the ventral tegmental area (VTA) also makes dopamine but is hit less.
- 1990: in 4 control brains, 5 Parkinson's brains and 1 striatonigral degeneration brain, nigral neurons containing calbindin-D28k (a protein that buffers calcium) were relatively spared compared with calbindin-negative, melanin-pigmented neurons, which sat mostly in the ventrolateral nigra. The abstract gives no percentages.
- 1992: counts showed more than 55% fewer midbrain dopamine neurons in Parkinson's than in age-matched controls: over 61% in the nigra plus retrorubral area, and over 42% in the VTA. A similar pattern of loss was seen in MPTP-treated monkeys, and calbindin cells sat in the spared regions in monkeys and mice.
Why it moved us toward a cure
It showed that vulnerability is not random and suggested a protective feature, calcium handling. Later landmarks took the idea on: the pattern of nigral tiers (landmark 267) and the SOX6/AGTR1 subtype (landmark 99).
Outcome
Open. The sparing is partial, since the VTA still lost over 42%, and calbindin is a marker that may not itself protect. Neither study tested protection.
Sources
- Yamada et al., Brain Res 1990;526:303–307, DOI 10.1016/0006-8993(90)91236-A
- German et al., Ann N Y Acad Sci 1992;648:42–62, DOI 10.1111/j.1749-6632.1992.tb24523.x
- Not yet verified: full texts (abstracts only, PMIDs 2257487 and 1353337); whether calbindin protects directly; the Yamada paper's volume is Brain Res 526 (from PubMed).
How it connects
Built on
- builds on Lewy bodies described; tied to the substantia nigra · 1912
Led to
- builds on Nigral cell loss pattern differs from ageing · 1991
- builds on The most vulnerable dopamine neuron subtype · 2022