Neuro-trauma
Promoting peripheral nerve regeneration by inhibiting a gene, miRNA-23a
Dr Rabia Islam
Deakin University
Co-Investigators : Professor Aaron Russell, Dr Victoria Foletta, Dr Paul Della Gatta, Dr Frederico Gerlinger-Romero

Project Summary:

When trauma or disease damages the connection between the motor nerves and skeletal muscle, muscle wasting occurs. This leads to impaired mobility, lack of independence and may even lead to death. Some of the peripheral nerves are able to repair and recover functional connections with skeletal muscle. However, the amount of nerve regeneration is often not sufficient. This leads to permanent muscle weakness, long-term disability and other health issues. Therefore, a major goal for treatment of nerve damage is to repair the nerve processes effectively and to facilitate maximal re-connection with muscle to allow full functional recovery.

In patients with motor neurone disease (MND) and mouse models of MND, we have observed that the progressive loss of motor neurons and muscle wasting, is associated with an increase in a small gene called miRNA-23a/miR-23a. We therefore postulated that miRNA-23a may contribute to motor neurone disease progression. Suppression of miRNA-23a may delay disease on-set and severity. Our preliminary studies revealed that miRNA-23a suppression in a mouse model of MND reduces muscle wasting and alleviates the loss of body weight. Furthermore, the mice display improved mobility and strength indicating improved muscle health and motor nerve connection with skeletal muscle. This was confirmed by further molecular analyses. Based on these results, we currently hypothesize that suppression of miRNA-23a will help form new motor nerve connections with skeletal muscle, thereby reducing muscle wasting and weakness. To test this hypothesis, we will investigate the effect of miRNA-23a inhibition on nerve repair using an acute nerve crush injury model. Following nerve crush injury, skeletal muscle strength and movement will be measured in mice with either normal or suppressed levels of miRNA-23a. The newly formed connections between muscle and nerve will also be imaged in muscle cross-sections.

These experiments will determine whether miRNA-23a is important for nerve regeneration. It will delineate the specific role it plays in the molecular pathways during regeneration. This information is a prerequisite for the development of potential new therapies for peripheral nerve injury and neuropathies.

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