Limits...
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

Effect of r-mTBI on diacyl-glycerophospholipid species detected in the present study based on degree of unsaturation.Saturated fatty acid species (SFA) are presented in green, monounsaturated fatty acid species (MUFA) are presented in blue, while polyunsaturated fatty acid species (PUFA) are presented in red. Symbols represent mean values of percent change of r-mTBI samples compared to r-sham samples; error bars indicate SEM. Note 1: due to the large number of PUFA species detected, only the ones showing > ±30% change are presented. Note 2: Species names covered with yellow boxes indicate statistical significance (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4835061&req=5

pone.0153608.g008: Effect of r-mTBI on diacyl-glycerophospholipid species detected in the present study based on degree of unsaturation.Saturated fatty acid species (SFA) are presented in green, monounsaturated fatty acid species (MUFA) are presented in blue, while polyunsaturated fatty acid species (PUFA) are presented in red. Symbols represent mean values of percent change of r-mTBI samples compared to r-sham samples; error bars indicate SEM. Note 1: due to the large number of PUFA species detected, only the ones showing > ±30% change are presented. Note 2: Species names covered with yellow boxes indicate statistical significance (p<0.05).

Mentions: Ether lysophosphatidylcholines (eLPC). Although this class of ether phospholipids was the least abundant of all ether phospholipids (0.6%), it was the most significantly upregulated in quantity of any phospholipid class in this study at 108.1% (p<0.001, t-test), and all four individual species that passed the detection criteria were significantly increased after TBI (Fig 5, 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)

Effect of r-mTBI on diacyl-glycerophospholipid species detected in the present study based on degree of unsaturation.Saturated fatty acid species (SFA) are presented in green, monounsaturated fatty acid species (MUFA) are presented in blue, while polyunsaturated fatty acid species (PUFA) are presented in red. Symbols represent mean values of percent change of r-mTBI samples compared to r-sham samples; error bars indicate SEM. Note 1: due to the large number of PUFA species detected, only the ones showing > ±30% change are presented. Note 2: Species names covered with yellow boxes indicate statistical significance (p<0.05).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0153608.g008: Effect of r-mTBI on diacyl-glycerophospholipid species detected in the present study based on degree of unsaturation.Saturated fatty acid species (SFA) are presented in green, monounsaturated fatty acid species (MUFA) are presented in blue, while polyunsaturated fatty acid species (PUFA) are presented in red. Symbols represent mean values of percent change of r-mTBI samples compared to r-sham samples; error bars indicate SEM. Note 1: due to the large number of PUFA species detected, only the ones showing > ±30% change are presented. Note 2: Species names covered with yellow boxes indicate statistical significance (p<0.05).
Mentions: Ether lysophosphatidylcholines (eLPC). Although this class of ether phospholipids was the least abundant of all ether phospholipids (0.6%), it was the most significantly upregulated in quantity of any phospholipid class in this study at 108.1% (p<0.001, t-test), and all four individual species that passed the detection criteria were significantly increased after TBI (Fig 5, 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