A 150-year-old staining quirk becomes a new window into brain cells
FutureNeuro researchers have turned a long-ignored gap in a classic stain into a way to measure a neuron’s nucleus and its branches at the same time, without slicing the brain.
For over 150 years, neuroscientists have used Golgi staining to make individual brain cells visible. The technique fills neurons with a dark metallic deposit, revealing their tree-like branches in striking detail. But the stain has a well-known quirk: it never enters the cell’s nucleus, the control centre that holds its DNA. That gap has long been treated as an artefact, something to work around.
In a new study published in Brain Research Bulletin, FutureNeuro researchers in Mamad’s Lab at RCSI University of Medicine and Health Sciences, led by Jordan Higgins and Dr Omar Mamad and working with colleagues at ZEISS, have turned this blind spot into a tool. They imaged intact mouse brain tissue using high-resolution 3D X-ray microscopy, where the stained cells show up bright. The unstained nucleus appears as a clean, sharply defined “hole” inside each cell. That hole lets the team measure the size, shape and position of the nucleus while also mapping the same neuron’s branches. Until now, this has been difficult, because seeing the nucleus usually means slicing the tissue, which cuts through the branches.
The X-ray scan doesn’t damage the tissue, so the same sample can be re-examined later with other techniques. The method also scales: a single scan of half a mouse brain picked up roughly 86,000 stained neurons.
The method has already turned up an intriguing early hint. In four of the five neurons the team reconstructed in full; the nucleus sat slightly off-centre, towards the branches at the base of the cell rather than the long branch that extends from its top. With so few cells, the researchers stress this is a lead to follow up rather than a finding.
The study is a proof-of-concept, and the team now plans larger studies to test ideas like this. They hope the method will help them explore whether changes in where the nucleus sits inside a neuron could be an early sign of disease in conditions such as epilepsy and neurodegeneration.
