Cell ablation is an important tool for selectively destroying one or multiple cells in a given organism to remove a disease such as cancer or to produce the desired response through the removal of specific genomic loci. A common form of ablation uses the diphtheria toxin, however, diphtheria crosses the blood-brain barrier which limits its utility for ablating cells in the peripheral nervous system (PNS). Now, a study from researchers at Instituto Gulbenkian de Ciencia develops a new genetic technique allowing the elimination of specific neurons in the PNS without affecting the same cells in the brain. The team states their novel technique opens new avenues for the study of many diseases related to the PNS and to other non-nerval 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 innervating the adipose tissue and demonstrated 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 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 or affect cells in the central nervous system. This toxin only kills cells containing its receptor, which mice typically do not have, meaning it must be artificially introduced into specific cells. Results show the successful elimination of neurons from the adipose tissue of mice, without affecting the brain. The group states mice with or without these catecholaminergic peripheral neurons exhibit similar eating patterns, however, mice lacking these catecholaminergic peripheral neurons gained fat very quickly.
The team surmises their technique allows for the verification of neurons innervating the adipose tissue to maintain normal adiposity and overcomes possible side effects in the brain. For the future, the researchers state the global medical community can now perform genetic ablation outside the brain and study the function of many peripheral cells for obesity, as well as other diseases.
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