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Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

Tzekov R, Dawson C, Orlando M, Mouzon B, Reed J, Evans J, Crynen G, Mullan M, Crawford F - PLoS ONE (2016)

Bottom Line: These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs.Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D.The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased.

View Article: PubMed Central - PubMed

Affiliation: The Roskamp Institute, Sarasota, FL, United States of America.

ABSTRACT
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI.

No MeSH data available.


Related in: MedlinePlus

Summary of the lipid classes and species detected in optic nerve tissue in the current study.
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pone.0153608.g004: Summary of the lipid classes and species detected in optic nerve tissue in the current study.

Mentions: Overall, 213 lipid species were identified to be present in the optic nerves above the lower limit of quantitation, distributed among 13 different glycerophospholipid and sphingolipid classes. The glycerophospholipids included ether lipid classes: ether phosphatidylcholine (ePC), ether lysophosphatidylcholine (eLPC), and ether phosphatidylethanolamine (ePE), and ester lipid classes: phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), and phosphatidylinositol (PI). Sphingolipids included the following classes: ceramide phosphoethanolamine (PE-Cer), sphingomyelin (SM), dihydrosphingomyelin (DSM), and sulfatide (SU) (Fig 4, S3 and S4 Tables). The total amount of phospholipids in the optic nerve tissue was decreased by 17.6% after r-mTBI, but this difference was not statistically significant. Out of the 13 classes, two ether lysophospholipid classes showed significant increase in total lipid quantity after r-mTBI (eLPC, eLPE) and in some individual molecular species. Furthermore, in five other classes (ePC, PC, PE, PLE, PI), individual lipid species showed either a significant increase or decrease in lipid quantity (Fig 4). The total amount of ether phospholipids and ester phospholipids were decreased to a similar extent (-17.2% vs. -18.6%, respectively) after r-mTBI, although for neither of the classes the decrease was statistically significant. However, in terms of change in individual species the pattern of change within the two classes was very different. Thus, 11 out of the 12 individual species (91.7%) significantly dysregulated after TBI showed increase in quantity after TBI for ether lipids compared to two out of the 22 species (9.1%) for ester lipids (Fig 4).


Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

Tzekov R, Dawson C, Orlando M, Mouzon B, Reed J, Evans J, Crynen G, Mullan M, Crawford F - PLoS ONE (2016)

Summary of the lipid classes and species detected in optic nerve tissue in the current study.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4835061&req=5

pone.0153608.g004: Summary of the lipid classes and species detected in optic nerve tissue in the current study.
Mentions: Overall, 213 lipid species were identified to be present in the optic nerves above the lower limit of quantitation, distributed among 13 different glycerophospholipid and sphingolipid classes. The glycerophospholipids included ether lipid classes: ether phosphatidylcholine (ePC), ether lysophosphatidylcholine (eLPC), and ether phosphatidylethanolamine (ePE), and ester lipid classes: phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), and phosphatidylinositol (PI). Sphingolipids included the following classes: ceramide phosphoethanolamine (PE-Cer), sphingomyelin (SM), dihydrosphingomyelin (DSM), and sulfatide (SU) (Fig 4, S3 and S4 Tables). The total amount of phospholipids in the optic nerve tissue was decreased by 17.6% after r-mTBI, but this difference was not statistically significant. Out of the 13 classes, two ether lysophospholipid classes showed significant increase in total lipid quantity after r-mTBI (eLPC, eLPE) and in some individual molecular species. Furthermore, in five other classes (ePC, PC, PE, PLE, PI), individual lipid species showed either a significant increase or decrease in lipid quantity (Fig 4). The total amount of ether phospholipids and ester phospholipids were decreased to a similar extent (-17.2% vs. -18.6%, respectively) after r-mTBI, although for neither of the classes the decrease was statistically significant. However, in terms of change in individual species the pattern of change within the two classes was very different. Thus, 11 out of the 12 individual species (91.7%) significantly dysregulated after TBI showed increase in quantity after TBI for ether lipids compared to two out of the 22 species (9.1%) for ester lipids (Fig 4).

Bottom Line: These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs.Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D.The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased.

View Article: PubMed Central - PubMed

Affiliation: The Roskamp Institute, Sarasota, FL, United States of America.

ABSTRACT
Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of several important molecular pathways. This will allow future identification of therapeutic targets for improving the visual consequences of r-mTBI.

No MeSH data available.


Related in: MedlinePlus