Category Archives: rat

On Leanness

Although many acknowledge that some people are inherently (perhaps genetically) leaner than others, it remains unclear what the biological basis for the body’s “set-point” might be. A study appearing in the open-access journal PLoS One suggests one possible factor1.

from reference 1

Both rat and human data were collected in this work, which concludes that “the lean phenotype is characterized by high endurance capacity and high activity and may stem from altered skeletal muscle energetics.” These researchers gathered data from a population of people who they categorized as non-exercisers (less than 1 hour per week of activity exceeding 4 METS). They subjected these individuals to a treadmill test to determine their endurance (as assessed by oxygen consumption during exercise) and kept track of their average daily activity over a period of 10 days; finding that there was a significant relationship between endurance and leanness, as well as average daily activity and leanness. Furthermore, they found that there was no significant difference in the amount of food consumed by lean versus non-lean rats, and fascinatingly, that the skeletal muscle tissue of lean rats has significantly higher levels of the enzyme PEPCK-C.

Of course, it is not surprising that those individuals with higher daily activity are leaner in general, rather, this study is suggesting that there may be a fundamental, biological reason why certain individuals are more active: they simply have a greater capacity for activity. Indeed, if one fatigues more easily, it wouldn’t be surprising if they were less active; it is also conceivable that reduced activity could feed-back on behavior in the sense that an individual with lower endurance might progressively reduce the amount of physical activity they engage in so as to reserve energy for other tasks. This is especially true in contemporary society, where mental activity is often the basis for work and play.

It is unclear as yet, however, whether the differential muscle-properties found in rats extend to humans; further work will be required to clarify what the molecular-biological basis for increased human endurance might be.

References
1. Novak CM, Escande C, Gerber SM, Chini EN, Zhang M, et al. (2009) Endurance Capacity, Not Body Size, Determines Physical Activity Levels: Role of Skeletal Muscle PEPCK. PLoS ONE 4(6): e5869. doi:10.1371/journal.pone.0005869

On Rodent Parkinsons

The cover of the journal Brain

Therapies based on stem cells rely heavily on our ability to coax these blank-cellular-slates into taking on specific forms. Stem cells are exciting as possible sources of medicinal therapy because they have the potential to become any type of cell in the body, but in order for their utility to be realized, we must be able to reliably effect their fates. The process of turning a stem cell into a specific cell type is called, logically, differentiation. With the exception of the immune system, the brain has more cell-types than any other organ, not to mention some of the most differentiated (exotic or distinct) types. Thus, many scientists are busily engaged in the activity of deducing molecular algorithms for deterministic control of their cellular end-state.

One disease where there seems to be a clear connection between cell-type-specific disfunction and pathology is Parkinson’s Disease. In this debilitating condition, the afflicted progressively loose motor function due to a lack of stimulation of their motor corticies (the area responsible for directing movement in the human brain) by dopaminergic neurons found in the amygdala (another brain region associated with emotion and reward). Further, it appears to be the case that the reason for this lack of stimulation is simply a lack of production of dopamine by these dopaminergic amygdalar neurons. The cell-type specificity of the disease makes it an an excellent candidate for treatment by replacing the existing hypoactive neurons with newly differentiated stem cell versions of their kind, which should have normal dopamine production abilities.

A recent paper appearing in the journal Brain reports the results of a study in which the researchers have achieved just such a therapeutic cell-type replacement in rats with a “model” of human Parkinson’s disease (ref. 1). They report that motor function was restored by this approach, and further that the longevity of the differentiated cells was related to their restorative efficacy. Further examples of work like this promise to revolutionize the treatment of a host of diseases.

References:
1. Sanchez-Pernaute R, Lee H, Patterson M, Reske-Nielsen C, Yoshizaki T, Sonntag KC, Studer L, Isacson O. (2008) Parthenogenetic dopamine neurons from primate embryonic stem cells restore function in experimental Parkinson’s disease. Brain.