Insulin-dependent maturation of newly generated olfactory se
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Insulin plays an important role in the regeneration of olfactory sensory neurons (OSNs) following a severe injury that induces cell death in many OSNs, according to a recent study in the journal eNeuro. The findings suggest that the insulin spray can be potentially applied for the treatment of smell loss for various reasons including head trauma and viral infection.

This study addresses how insulin receptor-mediated signaling affects the functional recovery of OSNs after OE injury. Insulin levels were reduced in mice by ablating the pancreatic beta cells via streptozotocin injections. These streptozotocin-induced diabetic and control mice were then intraperitoneally injected with the olfactotoxic drug methimazole to selectively ablate OSNs.

The OE of diabetic and control mice regenerated similarly until day 14 after injury. Thereafter, the OE of diabetic mice contained fewer mature and more apoptotic OSNs than control mice. Functionally, diabetic mice showed reduced electro-olfactogram responses and their olfactory bulbs had fewer c-Fos-active cells following odor stimulation, as well as performed worse in an odor-guided task compared to control mice.

Insulin administered intranasally during days 8 to 13 after injury was sufficient to rescue recovery of OSNs in diabetic mice compared to control levels, while insulin administration between days 1 – 6 did not. During this critical time window on days 8 – 13 after injury, insulin receptors are highly expressed and intranasal application of an insulin receptor antagonist inhibits regeneration.

Furthermore, an insulin-enriched environment could facilitate regeneration even in non-diabetic mice.

These results indicate that insulin facilitates the regeneration of OSNs after injury and suggest a critical stage during recovery during which the maturation of newly generated OSNs is highly dependent on and promoted by insulin.

Source: https://www.eneuro.org/content/early/2021/04/26/ENEURO.0168-21.2021
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