easibility of Mitochondrial Transplantation Via Nose‐To‐Brain Delivery for Treatment of Parkinson Diseases
Journal Title: Biomedical Journal of Scientific & Technical Research (BJSTR) - Year 2018, Vol 11, Issue 5
Abstract
Olfactory dysfunction has been recently identified as one of the earliest non-motor symptoms of Parkinson’s disease (PD); it occurs at an early stage in approximately 90% of patients with PD and can be observed several years before the onset of limb disorders. Although the mechanism of olfactory dysfunction and its association with PD remain unclear, same symptoms have been observed in patients with Alzheimer disease and Down syndrome. Therefore, it is confirmed that the close association between the olfactory bulb (OB) and cranial nerves plays an important role in neurodegeneration [1]. The OB affects the function of dopaminergic neurons. Recent studies have demonstrated that the repeat unilateral intra-nasal administration (i.n.) of the mitochondrial inhibitor rotenone for 3-7 days can damage dopaminergic neurons in both sides of the OB, thereby resulting in olfactory dysfunction; the inhibitory effect is more pronounced in the i.n. side. Therefore, the result suggests that rotenone affects neuronal function via olfactory transport [2]. Meanwhile, unilateral i.n. induces dopaminergic neuron damage in both sides of the OB, indicating that neurotoxins spread to the brain via olfactory transport [2]. Therefore, i.n. may regulate brain cell functions, such as the mitochondrial functions of dopaminergic neurons via olfactory transport. Further studies confirming whether the i.n. of neurotoxins can chronically induce dopaminergic neuron death in the substantia nigra (SN) are warranted [3]; however, most studies have suggested that the delivery of inhaled environmental toxins via olfactory transport is one of the main inducers of spontaneous neurodegenerative diseases such as PD [4]. The development of effective genetic or drug therapy for PD has always been a hotspot in research. However, the efficacy of treatments is limited mainly because the delivery of therapeutic substances is hampered due to the inability of large biomolecules to cross the blood–brain barrier (BBB). One solution is to perform intra-cerebral infusion directly at the location of the lesion. In recent years, studies have confirmed the efficacy of the i.n. of nanomedicines in the treatment of PD [5]. A study found that i.n. is an effective route, which not only reduces brain tissue damage as a non-surgical method but also provides a new way to bypass the BBB via the olfactory and trigeminal neural pathways, which connect the nasal mucosa to the perivascular pathways in the brain and central nervous system (CNS) [6]. Simultaneously, the i.n. route bypasses the cardiovascular system, reduces the metabolism of drugs in the liver and increases drug utilisation, thereby providing an effective method for non-invasive drug delivery to the CNS [7]. In addition to the olfactory and trigeminal neural pathways, the study have also found that the i.n. of drugs or neurotransmitters allows these drugs to cross the nasal cavity, enter the cerebrospinal fluid (CSF) and be directly transported to the brain via the blood–CSF barrier (BCSFB) [8]. Unlike the BBB, which is formed by endothelial cells, BCSFB is located at the cerebral choroid plexus and comprises epithelial cells. Its functions are similar to that of the BBB, but with lower selectivity and higher permeability than the BBB to maintain CSF production by eliminating waste, maintaining neurotransmitter homeostasis and accelerating intra-cerebral substance transfer [8].
Authors and Affiliations
Jui-Chih Chang, Yi-Chun Chao, Huei-Shin Chang, Hui-Ju Chang, Wen-Ling Cheng, Ta-Tsung Lin, Chin-San Liu
Keywords
Related Articles
- EP ID EP592713
- DOI 10.26717/BJSTR.2018.11.002158
- Views 195
- Downloads 0
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