Researchers successfully eliminate neurons outside the brain to trigger obesity.

Specific cell ablation is an important tool for selectively destroying one or multiple cells in a given organism.  For example, a laser beam or a controllable gene can be used to destroy a selected amount of cells. Cell ablation can also be used as a tool to produce transgenic organisms lacking a cell type or as a cure for certain disorders such as cancer.  A common form of ablation uses the diptheria toxin, however, diphtheria crosses the blood–brain barrier which limits its utility for ablating peripheral cells using Cre drivers which are also expressed in the central nervous system.  Now, a study from researchers at Instituto Gulbenkian de Ciencia develops a new genetic technique which allows the elimination of specific neurons in the peripheral nervous system without affecting the same cells in the brain. The team state that their novel technique opens new avenues for the study of many diseases related to the peripheral nervous system and to other cells outside the brain.  The opensource study is published in the journal Nature Communications.

Earlier studies from the lab recently discovered a set of peripheral catecholaminergic neurons which innervate the adipose tissue, and demonstrated that the direct activation of these neurons burned fat. The current study investigates whether mice become obese in the absence of these peripheral neurons, without affecting similar neurons which also exist in the brain.

The current study develops a chemically-modified diphtheria toxin, increasing the size of the molecule so it can’t traverse the blood-brain barrier to effect cells in the central nervous system.  This toxin only kills cells that contain its receptor, which mice typically do not have, unless it is artificially introduced in specific cells.  Results show successful elimination of neurons from the adipose tissue of mice, without affecting the brain.  The group state that mice with or without these catecholaminergic peripheral neurons exhibit similar eating patterns, however, the mice  that lack catecholaminergic peripheral neurons gained fat very quickly.

The team surmise their technique allows the verification of neurons which innervate the adipose tissue to maintain a normal adiposity, and overcomes possible side effects in the brain which could result from the limitations of the gold standard technique. For the future, the researchers state that the global medical community can now perform genetic ablation outside the brain and study the function of many peripheral cells for obesity, and many other diseases.

Source: Instituto Gulbenkian de Ciencia (IGC; Portugal)

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