Nose ‐To ‐Brain Delivery of Mitochondria for Treatment of Parkinson’s Disease Model Rats With 6-Hydroxydopamine

Abstract

BackgroundFeasibility of mitochondrial organelle transport via the olfactory bulb route for Parkinson's disease (PD) therapy was evaluated in the unilateral 6-OHDA-lesioned rats due to the distinct difference based on payload properties. MethodsAn intranasal infusion with 200 μg of allogeneic mitochondria conjugated with Pep-1 (P-Mito) or not (Mito) was executed once a week at the ipsilateral side of lesioned brain for three months of treatments.Results A significant improvement of rotational and locomotor behaviors in PD rats was found in both mitochondria-treating groups in contrast to Sham group or Pep-1 group. There was more than 60% recovery survival of dopaminergic (DA) neurons in substantia nigra (SN) and striatum (ST) of lesioned sides compared to the intact sides in groups of Mito and P-Mito. Treatment effect in P-Mito group was higher in the P-Mito group than Mito group but not significant. The mechanism was associated with the restoration of mitochondrial function and attenuation of oxidative damage in lesioned SN. Notably, Pep-1 modification suppressed the plasma level of inflammatory cytokines induced by infused mitochondria. The 5-bromo-2-deoxyuridine-labelled tracks showed the mitochondrial penetrating into doublecortin-positive neurons of rostral migratory stream (RMS) along with the accessory olfactory bulb in ipsilateral side of lesion and it was expressed in striatal DA neurons, but not in SN, of two cerebral hemispheres via commissural fibers. Conclusion This study showed a promising approach of nose-to-brain delivery for mitochondrial transplantation by confirming the mitochondrial internalization via RMS neurons migration in olfactory bulb for therapeutic action of PD in rats.

Platelet-derived microparticles provoke chronic lymphocytic leukemia malignancy through metabolic reprogramming

“…Mitochondrial transfer (or "mito-transfer") is a well described phenomenon amongst cell types and has been shown to modulate recipient cell metabolic function (65)(66)(67). Since metabolic plasticity represents a hallmark of cancer progression, we investigated the impact of PMP internalization, or Set2-purified mitochondria, on several mitochondrial functions of our human leukemic cell models.…”

“…However, these findings were shown to be physiologically confined to neural and glia cell activation processes. Mito-transfer events have also been described using other routes of allocation such as tunneling nanotubes (TNT), Cx43 gap junctions, and transplantation, all of which result in recipient cell metabolic changes (65)(66)(67). Nonetheless, given that platelets represent the largest source of microparticles in the human body, PMPs therefore represent a significant means for mitochondrial acquisition into permissive cancer cells (27,28,91,92).…”

Silymarin Potentiates the Effect of Buspirone on Anxiety and Depressive-Like Behaviors Induced by Chronic Restraint Stress in Male Mice

“…It imposes a heavy burden on communities. 18,19 Benzodiazepine drugs have been a choice therapy for anxiety symptoms for several decades. These drugs have well-known side effects such as drowsiness, lethargy, cognitive and motor impairment, and depression in some patients despite the effective anxiolytic impact.…”