Fight Aging!

In recent years, there has been an increasing interest in the ability of cells to transfer mitochondria and take up mitochondria from the surrounding environment. In many ways, mitochondria are treated like just another type of extracellular vesicle - except that, of course, mitochondria are much more complex and functional, capable of replication. Researchers have noted examples of cells aiding the function of other cells in this way, and also found that introducing mitochondria in large numbers may form the basis for therapies. Several companies (including Cellvie and Mitrix Bio) are at present working to build the infrastructure needed for widespread use of mitochondrial transplant therapies. There will be clinical trials of the first such therapies in the years ahead, the trajectory seems well established now.

Along the way to those human trials, as interest in mitochondrial transfer grows, we will see more technology demonstrations in animals, such as the one described in today's research materials. The scientists involved have shown that supporting astrocyte cells in the brain will transfer mitochondria to neurons following brain injury, and that this helps to reduce the resulting damage. Further, introducing mitochondria harvested from astrocytes produces benefits. These demonstrations will help to identify the most plausible early uses for mitochondrial transplant therapies.

Brain support cells transfer their mitochondria to fight free radicals

An artery in the brain bursts. Blood rushes into the tissue, inducing free radicals that cause even more damage. The hemorrhage damages mitochondria, the site of energy production in cells. Astrocytes transfer their mitochondria to damaged neurons after a hemorrhage. These healthy mitochondria contain a "healing" peptide called humanin and an enzyme called manganese superoxide dismutase (Mn-SOD) that help neutralize free radicals.

Researchers injected mice with healthy mitochondria after a hemorrhage. The hemorrhage reduced levels of Mn-SOD in the mice brain and increased the number of free radicals. Using molecular tags, the researchers found that the rodents' neurons took up the mitochondria from the bloodstream. The mice who received the treatment showed improved neurological recovery, but the benefits decreased if the mice received mitochondria without the Mn-SOD enzyme. These results reveal mitochondria can transfer between brain cells to improve health and aide recovery.

Transplantation of astrocytic mitochondria modulates neuronal antioxidant defense and neuroplasticity and promotes functional recovery after intracerebral hemorrhage

Astrocytes release functional mitochondria (Mt) that play regulatory and pro-survival functions upon entering adjacent cells. We recently demonstrated that these released Mt could enter microglia to promote their reparative/pro-phagocytic phenotype that assists in hematoma cleanup and neurological recovery after intracerebral hemorrhage (ICH). However, a relevance of astrocytic Mt transfer into neurons in protecting brain after ICH is unclear. Here, we found that ICH causes a robust increase in superoxide generation and elevated oxidative damage that coincides with loss of the mitochondrial enzyme manganese superoxide dismutase (Mn-SOD). The damaging effect of ICH was reversed by intravenous transplantation of astrocytic Mt that upon entering the brain (and neurons), restored Mn-SOD levels and reduced neurological deficits in male mice subjected to ICH.

Using an in vitro ICH-like injury model in cultured neurons, we established that astrocytic Mt upon entering neurons prevented reactive oxygen species-induced oxidative stress and neuronal death by restoring neuronal Mn-SOD levels, while at the same time promoted neurite extension and upregulation of synaptogenesis-related gene expression. Furthermore, we found that Mt genome-encoded small peptide humanin (HN) that is normally abundant in Mt, could simulate Mt-transfer effect on neuronal Mn-SOD expression, oxidative stress, and neuroplasticity under ICH-like injury. This study demonstrates that adoptive astrocytic Mt transfer enhances neuronal Mn-SOD-mediated anti-oxidative defense and neuroplasticity in the brain, which potentiate functional recovery following ICH.