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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

Quantitative assessment of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and lysophosphatidylethganolamine (LPE) in optic nerve samples at 3 weeks after injury.Significant changes in individual molecular species together with changes in the total amount of lipids in the respective classes are shown. Upper panel—changes in PC, middle panel—changes in LPC, lower panel—changes in LPE species. Color coding and asterisk association same as in Fig 5.
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pone.0153608.g006: Quantitative assessment of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and lysophosphatidylethganolamine (LPE) in optic nerve samples at 3 weeks after injury.Significant changes in individual molecular species together with changes in the total amount of lipids in the respective classes are shown. Upper panel—changes in PC, middle panel—changes in LPC, lower panel—changes in LPE species. Color coding and asterisk association same as in Fig 5.

Mentions: Ether lysophosphatidylethanolamines (eLPE). Similar to the changes observed in eLPC, the overall amount of eLPE, which is another minor ether lipid class (2.8% of all ether phospholipids), was significantly increased after TBI by 60.0% (p<0.05). Of the seven species showing an increase after TBI, in four species the increase was found to be statistically significant: eLPE(0–16:1), eLPE(0–18:0), eLPE(0–18:1), and eLPE(0–18:2) (Fig 6, S4 Table, Fig 8).


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)

Quantitative assessment of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and lysophosphatidylethganolamine (LPE) in optic nerve samples at 3 weeks after injury.Significant changes in individual molecular species together with changes in the total amount of lipids in the respective classes are shown. Upper panel—changes in PC, middle panel—changes in LPC, lower panel—changes in LPE species. Color coding and asterisk association same as in Fig 5.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153608.g006: Quantitative assessment of phosphatidylcholine (PC), lysophosphatidylcholine (LPC) and lysophosphatidylethganolamine (LPE) in optic nerve samples at 3 weeks after injury.Significant changes in individual molecular species together with changes in the total amount of lipids in the respective classes are shown. Upper panel—changes in PC, middle panel—changes in LPC, lower panel—changes in LPE species. Color coding and asterisk association same as in Fig 5.
Mentions: Ether lysophosphatidylethanolamines (eLPE). Similar to the changes observed in eLPC, the overall amount of eLPE, which is another minor ether lipid class (2.8% of all ether phospholipids), was significantly increased after TBI by 60.0% (p<0.05). Of the seven species showing an increase after TBI, in four species the increase was found to be statistically significant: eLPE(0–16:1), eLPE(0–18:0), eLPE(0–18:1), and eLPE(0–18:2) (Fig 6, S4 Table, Fig 8).

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