Stem cell transplant restores memory, learning in mice

Scientists have for the first time transformed human embryonic stem cells into nerve cells to help mice regain the ability to learn and remember.
The study by the University of Wisconsin-Madison in US is the first to show that human stem cells can successfully implant themselves in the brain and then heal neurological deficits.
Once inside the mouse brain, the implanted stem cells formed two common, vital types of neurons, which communicate with the chemicals GABA or acetylcholine.
"These two neuron types are involved in many kinds of human behaviour, emotions, learning, memory, addiction and many other psychiatric issues," said senior author Su-Chun Zhang, a professor of neuroscience and neurology.

The human embryonic stem cells were cultured in the lab, using chemicals that are known to promote development into nerve cells. The mice were a special strain that do not reject transplants from other species.
After the transplant, the mice scored significantly better on common tests of learning and memory in mice. For example, they were more adept in the water maze test, which challenged them to remember the location of a hidden platform in a pool.

The study began with deliberate damage to a part of the brain that is involved in learning and memory.
"Developing brain cells get their signals from the tissue that they reside in, and the location in the brain we chose directed these cells to form both GABA and cholinergic neurons," Zhang said.

The initial destruction was in an area called the medial septum, which connects to the hippocampus by GABA and cholinergic neurons.
"This circuitry is fundamental to our ability to learn and remember," Zhang said.
The transplanted cells, however, were placed in the hippocampus - a vital memory center - at the other end of those memory circuits.
After the transferred cells were implanted, in response to chemical directions from the brain, they started to specialise and connect to the appropriate cells in the hippocampus.
For the study, published in the journal Nature Biotechnology, Zhang and first author Yan Liu, a postdoctoral associate at the Waisman Center on campus, chemically directed the human embryonic stem cells to begin differentiation into neural cells, and then injected those intermediate cells.

Brain repair through cell replacement is a Holy Grail of stem cell transplant, and the two cell types are both critical to brain function, Zhang said.
"Cholinergic neurons are involved in Alzheimer's and Down syndrome, but GABA neurons are involved in many additional disorders, including schizophrenia, epilepsy, depression and addiction," Zhang said.