Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates
Minimal myelination is proposed to be a contributing factor to the preferential nigral neuronal loss in Parkinson’s disease (PD). Similar to nigral dopaminergic neurons, sympathetic neurons innervating the heart have long, thin axons which are unmyelinated or minimally myelinated. Interestingly, car...
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| Format: | Article |
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Wiley
2021-01-01
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| Series: | Neurology Research International |
| Online Access: | http://dx.doi.org/10.1155/2021/4776610 |
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| author | Jeanette M. Metzger Helen N. Matsoff Don Vu Alexandra D. Zinnen Kathryn M. Jones Viktoriya Bondarenko Heather A. Simmons Colleen F. Moore Marina E. Emborg |
| author_facet | Jeanette M. Metzger Helen N. Matsoff Don Vu Alexandra D. Zinnen Kathryn M. Jones Viktoriya Bondarenko Heather A. Simmons Colleen F. Moore Marina E. Emborg |
| author_sort | Jeanette M. Metzger |
| collection | DOAJ |
| description | Minimal myelination is proposed to be a contributing factor to the preferential nigral neuronal loss in Parkinson’s disease (PD). Similar to nigral dopaminergic neurons, sympathetic neurons innervating the heart have long, thin axons which are unmyelinated or minimally myelinated. Interestingly, cardiac sympathetic loss in PD is heterogeneous across the heart, yet the spatial relationship between myelination and neurodegeneration is unknown. Here, we report the mapping of myelin basic protein (MBP) expression across the left ventricle of normal rhesus macaques (n = 5) and animals intoxicated with systemic 6-OHDA (50 mg/kg iv) to model parkinsonian cardiac neurodegeneration (n = 10). A subset of 6-OHDA-treated rhesus received daily dosing of pioglitazone (5 mg/kg po; n = 5), a PPARγ agonist with neuroprotective properties. In normal animals, MBP-immunoreactivity (-ir) was identified surrounding approximately 14% of axonal fibers within nerve bundles of the left ventricle, with more myelinated nerve fibers at the base level of the left ventricle than the apex p<0.014. Greater MBP-ir at the base was related to a greater number of nerve bundles at that level relative to the apex p<0.05, as the percent of myelinated nerve fibers in bundles was not significantly different between levels of the heart. Cardiac sympathetic loss following 6-OHDA was associated with decreased MBP-ir in cardiac nerve bundles, with the percent decrease of MBP-ir greater in the apex (84.5%) than the base (52.0%). Interestingly, cardiac regions and levels with more MBP-ir in normal animals showed attenuated sympathetic loss relative to areas with less MBP-ir in 6-OHDA + placebo (r = −0.7, p<0.014), but not in 6-OHDA + pioglitazone (r = −0.1) subjects. Our results demonstrate that myelination is present around a minority of left ventricle nerve bundle fibers, is heterogeneously distributed in the heart of rhesus macaques, and has a complex relationship with cardiac sympathetic neurodegeneration and neuroprotection. |
| format | Article |
| id | doaj-art-a4c324a8bc6b4c45b187e3a40b02e364 |
| institution | OA Journals |
| issn | 2090-1852 2090-1860 |
| language | English |
| publishDate | 2021-01-01 |
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| spelling | doaj-art-a4c324a8bc6b4c45b187e3a40b02e3642025-08-20T02:23:05ZengWileyNeurology Research International2090-18522090-18602021-01-01202110.1155/2021/47766104776610Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman PrimatesJeanette M. Metzger0Helen N. Matsoff1Don Vu2Alexandra D. Zinnen3Kathryn M. Jones4Viktoriya Bondarenko5Heather A. Simmons6Colleen F. Moore7Marina E. Emborg8Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USADepartment of Psychology, University of Wisconsin-Madison, Madison, WI 53715, USAWisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715, USAMinimal myelination is proposed to be a contributing factor to the preferential nigral neuronal loss in Parkinson’s disease (PD). Similar to nigral dopaminergic neurons, sympathetic neurons innervating the heart have long, thin axons which are unmyelinated or minimally myelinated. Interestingly, cardiac sympathetic loss in PD is heterogeneous across the heart, yet the spatial relationship between myelination and neurodegeneration is unknown. Here, we report the mapping of myelin basic protein (MBP) expression across the left ventricle of normal rhesus macaques (n = 5) and animals intoxicated with systemic 6-OHDA (50 mg/kg iv) to model parkinsonian cardiac neurodegeneration (n = 10). A subset of 6-OHDA-treated rhesus received daily dosing of pioglitazone (5 mg/kg po; n = 5), a PPARγ agonist with neuroprotective properties. In normal animals, MBP-immunoreactivity (-ir) was identified surrounding approximately 14% of axonal fibers within nerve bundles of the left ventricle, with more myelinated nerve fibers at the base level of the left ventricle than the apex p<0.014. Greater MBP-ir at the base was related to a greater number of nerve bundles at that level relative to the apex p<0.05, as the percent of myelinated nerve fibers in bundles was not significantly different between levels of the heart. Cardiac sympathetic loss following 6-OHDA was associated with decreased MBP-ir in cardiac nerve bundles, with the percent decrease of MBP-ir greater in the apex (84.5%) than the base (52.0%). Interestingly, cardiac regions and levels with more MBP-ir in normal animals showed attenuated sympathetic loss relative to areas with less MBP-ir in 6-OHDA + placebo (r = −0.7, p<0.014), but not in 6-OHDA + pioglitazone (r = −0.1) subjects. Our results demonstrate that myelination is present around a minority of left ventricle nerve bundle fibers, is heterogeneously distributed in the heart of rhesus macaques, and has a complex relationship with cardiac sympathetic neurodegeneration and neuroprotection.http://dx.doi.org/10.1155/2021/4776610 |
| spellingShingle | Jeanette M. Metzger Helen N. Matsoff Don Vu Alexandra D. Zinnen Kathryn M. Jones Viktoriya Bondarenko Heather A. Simmons Colleen F. Moore Marina E. Emborg Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates Neurology Research International |
| title | Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates |
| title_full | Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates |
| title_fullStr | Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates |
| title_full_unstemmed | Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates |
| title_short | Myelin Basic Protein and Cardiac Sympathetic Neurodegeneration in Nonhuman Primates |
| title_sort | myelin basic protein and cardiac sympathetic neurodegeneration in nonhuman primates |
| url | http://dx.doi.org/10.1155/2021/4776610 |
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