Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI).
Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical an...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4902227?pdf=render |
| _version_ | 1818410113277362176 |
|---|---|
| author | Renana Baratz-Goldstein Hanna Deselms Leore Raphael Heim Lena Khomski Barry J Hoffer Daphne Atlas Chaim G Pick |
| author_facet | Renana Baratz-Goldstein Hanna Deselms Leore Raphael Heim Lena Khomski Barry J Hoffer Daphne Atlas Chaim G Pick |
| author_sort | Renana Baratz-Goldstein |
| collection | DOAJ |
| description | Mild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries. |
| first_indexed | 2024-12-14T10:10:21Z |
| format | Article |
| id | doaj.art-7ac519ef0c3741b7aced98dfae0f2126 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T10:10:21Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7ac519ef0c3741b7aced98dfae0f21262022-12-21T23:07:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01116e015706410.1371/journal.pone.0157064Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI).Renana Baratz-GoldsteinHanna DeselmsLeore Raphael HeimLena KhomskiBarry J HofferDaphne AtlasChaim G PickMild traumatic brain injury (mTBI) is recognized as a common injury among children, sportsmen, and elderly population. mTBI lacks visible objective structural brain damage but patients frequently suffer from long-lasting cognitive, behavioral and emotional difficulties associated with biochemical and cellular changes. Currently there is no effective treatment for patients with mTBI. The thioredoxin reductase/thioredoxin pathway (TrxR/Trx1) has both anti-inflammatory and anti-oxidative properties. If the system is compromised, Trx1 remains oxidized and triggers cell death via an ASK1-Trx1 signal transduction mechanism. We previously showed tri and tetra peptides which were derived from the canonical -CxxC- motif of the Trx1-active site, called thioredoxin mimetic (TXM) peptides, reversed inflammatory and oxidative stress damage mimicking Trx1 activity. Here, TXM-peptides were examined for protecting cognitive function following weight drop closed-head injury in a mouse model of mTBI. TXM-CB3 (AcCys-Pro-CysNH2), TXM-CB13 (DY-70; AcCys-Met-Lys-CysNH2) or AD4 (ACysNH2) were administered at 50 mg/kg, 60 min after injury and cognitive performance was monitored by the novel-object-recognition and Y-maze tests. Behavioral deficits subsequent to mTBI injury were reversed by a single dose of TXM-CB3, TXM-CB13 and, to a lesser extent, by AD4. TXM-CB13 similar to TXM-CB3 and AD4 reversed oxidative stress-induced phosphorylation of mitogen-activated kinases, p38MAPK and c-Jun N-terminal kinase, (JNK) in human neuronal SH-SY5Y cells. We conclude that significantly improved cognitive behavior post mTBI by the TXM-peptides could result from anti-apoptotic, and/or anti-inflammatory activities. Future preclinical studies are required to establish the TXM-peptides as potential therapeutic drugs for brain injuries.http://europepmc.org/articles/PMC4902227?pdf=render |
| spellingShingle | Renana Baratz-Goldstein Hanna Deselms Leore Raphael Heim Lena Khomski Barry J Hoffer Daphne Atlas Chaim G Pick Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). PLoS ONE |
| title | Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). |
| title_full | Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). |
| title_fullStr | Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). |
| title_full_unstemmed | Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). |
| title_short | Thioredoxin-Mimetic-Peptides Protect Cognitive Function after Mild Traumatic Brain Injury (mTBI). |
| title_sort | thioredoxin mimetic peptides protect cognitive function after mild traumatic brain injury mtbi |
| url | http://europepmc.org/articles/PMC4902227?pdf=render |
| work_keys_str_mv | AT renanabaratzgoldstein thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi AT hannadeselms thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi AT leoreraphaelheim thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi AT lenakhomski thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi AT barryjhoffer thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi AT daphneatlas thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi AT chaimgpick thioredoxinmimeticpeptidesprotectcognitivefunctionaftermildtraumaticbraininjurymtbi |