Yes, this is another ‘works in mice’ procedure. The type of neuron created in the study, one associated with muscle control, is the type damaged by ALS (amyotrophic lateral sclerosis or Lou Gehrig disease). If it can be shown that a stem cell transplant will repair or replace these damaged neurons…there are a lot of people waiting. Crossing the gap from Petri dish to use in a living mammal brain is much wider than the gap of moving from mouse to human brain, although the latter gap requires much more laborious bridging (e.g. testing and official approval).

Until now, making these proper cellular connections has been a fundamental problem in nervous system transplant therapy. In this case, the maturing neurons extended to the appropriate brain structures, and, just as importantly, avoided inappropriate areas. For example, cells transplanted into the visual cortex reached two deep brain structures called the superior colliculus and the pons, but not to the spinal cord; cells placed into the motor area of the cortex stretched into the spinal cord but avoided the colliculus.

[Source: Cell News]

The major advances in this study involve the preparation of stem cells in the Petri dish – a complex matter of nutrients, environment, and appropriate chemistry. Once the cells were partially differentiated, they could much more easily integrate with the neurons in the mouse brain. Here too, advances were made in the placement and growth environment within the brain of the newborn mice. Ultimately the research showed the ability to create the right kind of cell and make the right kind of connectivity within the brain; something of a first with stem cells. The next steps are to attempt the same kind of transplant in adult animals (mostly mice again). Much later, given success, the transplants may be tried with humans.

The field of chronobiology (the science of periodic and cyclic phenomena in living creatures) was developed during the 1960’s, although the history of scientific interest in the 24 hour cycle in plants and animals dates back to the 18th century. What is now called the circadian rhythm, corresponding to the 24 hours of an Earth day, is one mechanism by which living things can orient internal processes with physical reality. With an internal clock the hours for feeding, resting and other activities can be more or less synchronized with events such as daylight and darkness. Even some forms of bacteria, for example cyanobacteria (blue-green algae), have demonstrated a circadian clock.

The sleep-wake cycle, the most characterized manifestation of the circadian clock, is generated thanks to specialized neurons found both in humans and fruitflies. (The mechanism governing the circadian clock in fruitflies is almost identical to the one mammals — and humans — have.)

These neurons have the striking capability of counting time very accurately via a complex process of gene activation and repression that result in a tightly controlled process that takes exactly 24 hours.

The new research by Dr. Kadener and his colleagues, published in an article in the journal Genes and Development (and that was highlighted in Nature Review Neuroscience), has shown that a new mode of regulation has a pivotal importance for the ability of our internal clock to accurately count those 24 hours each day. Specifically, they have shown that the very tiny miRNA [microRNA, single stranded RNA molecules, which regulate gene expression] are necessary for the circadian rhythms to function.

MiRNAs have recently been discovered and have been shown to be involved in different processes in animals. By the use of new state-of-the-art techniques (most of them developed in the present study) the authors demonstrate that one specific miRNA (called bantam) recognizes and regulates the translation of the gene clock. This constitutes the first example of a defined miRNA-gene regulation in the central clock.

[Source: Hebrew University]