Dataset Information

Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice.

ABSTRACT: 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.

SUBMITTER: Bobkova NV

PROVIDER: S-EPMC8919317 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice.

Bobkova Natalia V NV Zhdanova Daria Y DY Belosludtseva Natalia V NV Penkov Nikita V NV Mironova Galina D GD

Experimental biology and medicine (Maywood, N.J.) 20211102 5

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 ...[more]

PMID: 34727745

Similar Datasets

Project description:Iron is the most abundant transition metal in the brain and is essential for brain development and neuronal function; however, its abnormal accumulation is also implicated in various neurological disorders. The olfactory bulb (OB), an early target in neurodegenerative diseases, acts as a gateway for environmental toxins and contains diverse neuronal populations with distinct roles. This study explored the cell-specific vulnerability to iron in the OB using a mouse model of intranasal administration of ferric ammonium citrate (FAC). Olfactory function was assessed through olfactory discrimination tests, while iron levels in OB tissues, cerebrospinal fluid (CSF), and serum were quantified using inductively coupled plasma mass spectrometry (ICP-MS), immunohistochemical staining, and iron assays. Transcriptomic changes and immune responses were assessed using RNA sequencing and immune cell infiltration analysis. Results showed that intranasal FAC administration impaired olfactory function, accompanied by iron deposition in the olfactory mucosa and OB, as well as damage to olfactory sensory neurons. Notably, these effects occurred without elevations in CSF or serum iron levels. OB iron accumulation activated multiple immune cells, including microglia and astrocytes, but did not trigger ferroptosis. Spatial transcriptomic sequencing of healthy adult mouse OBs revealed significant cellular heterogeneity, with an abundance of neuroglia and neurons. Among neurons, GABAergic neurons were the most prevalent, followed by glutamatergic and dopaminergic neurons, while cholinergic and serotonergic neurons were sparsely distributed. Under iron-stressed conditions, oligodendrocytes, dopaminergic neurons, and glutamatergic neurons exhibited significant damage, while GABAergic neurons remained unaffected. These findings highlight the selective vulnerability of neuronal and glial populations to iron-induced stress, offering novel insights into the loss of specific cell types in the OB during iron dysregulation.

Dataset Information

Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice.

Publications

Intranasal administration of mitochondria improves spatial memory in olfactory bulbectomized mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets