Journal
EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 247, Issue 5, Pages 416-425Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1177/15353702211056866
Keywords
Mitochondrial therapy; intranasal microinjections; spatial memory; olfactory bulbectomized mice; neurodegenerative diseases; mitochondrial dysfunction
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Funding
- Russian Science Foundation [18-15-00392]
- Russian Foundation for Basic Research [20-015-00029ff]
- Russian Science Foundation [18-15-00392] Funding Source: Russian Science Foundation
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The study showed that intranasal administration of mitochondria improved spatial memory in mice with Alzheimer's type degeneration. Colocalization of allogeneic mitochondria with markers of astrocytes and neurons was observed in hippocampal cell culture.
Here, we found that functionally active mitochondria isolated from the brain of NMRI donor mice and administrated intranasally to recipient mice penetrated the brain structures in a dose-dependent manner. The injected mitochondria labeled with the MitoTracker Red localized in different brain regions, including the neocortex and hippocampus, which are responsible for memory and affected by degeneration in patients with Alzheimer's disease. In behavioral experiments, intranasal microinjections of brain mitochondria of native NMRI mice improved spatial memory in the olfactory bulbectomized (OBX) mice with Alzheimer's type degeneration. Control OBX mice demonstrated loss of spatial memory tested in the Morris water maze. Immunocytochemical analysis revealed that allogeneic mitochondria colocalized with the markers of astrocytes and neurons in hippocampal cell culture. The results suggest that a non-invasive route intranasal administration of mitochondria may be a promising approach to the treatment of neurodegenerative diseases characterized, like Alzheimer's disease, by mitochondrial dysfunction.
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