PMID- 23251488 OWN - NLM STAT- MEDLINE DCOM- 20130611 LR - 20220409 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 7 IP - 12 DP - 2012 TI - Endogenous repair by the activation of cell survival signalling cascades during the early stages of rat Parkinsonism. PG - e51294 LID - 10.1371/journal.pone.0051294 [doi] LID - e51294 AB - Here we report a previously unknown self repair mechanism during extremely early stages of rat Parkinsonism. Two important cell survival signaling cascades, Phosphatidylinositol-3 kinases (PI3K)/Akt pathway and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway, could be responsible for this potential endogenous rescue system. In the 6-hydroxydopamine-lesioned rat, the phosphorylated p44/42 MAPK and its downstream target, the phosphorylated Bad at Ser 112, were up-regulated at post-lesion day 3 and lasted for a couple of weeks. Although the change in the phosphorylated Akt kinase was negligible throughout the studied period, its downstream target, the phosphorylated Bad at 136, was increased from post-lesion day 3 to post-lesion day 14. In the mean time, nestin-positive reactive astrocytes with low levels of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) appeared at post-lesion day 3 in 6-hydroxydopamine-lesioned rat. BDNF was expressed in both striatum and substantia nigra whereas GDNF was displayed in striatum only. At post-lesion day 14, nestin, BDNF and GDNF expressions were diminished. These neurotrophic factors were believed to initiate the above anti-apoptotic signal transduction cascades as we could see that their expression patterns were similar. The data strongly suggest that there is an endogenous repair effort by evoking the cell survival signaling and possibly via the releases of BDNF and GDNF from nestin-immunoreactive reactive astrocytes. ERK/MAPK pathway was proposed to be the key endogenous neuroprotective mechanisms, particularly in early stages of rat Parkinsonism. However, the self repair effort is only functional within an extremely short time window immediately after onset. FAU - Lui, Nga-Ping AU - Lui NP AD - Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong. FAU - Chen, Liang-Wei AU - Chen LW FAU - Yung, Wing-Ho AU - Yung WH FAU - Chan, Ying-Shing AU - Chan YS FAU - Yung, Ken Kin-Lam AU - Yung KK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20121212 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 8HW4YBZ748 (Oxidopamine) RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Blotting, Western MH - *Cell Survival MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Antibody Technique MH - Mitogen-Activated Protein Kinases/metabolism MH - Oxidopamine/toxicity MH - Parkinsonian Disorders/metabolism/*pathology MH - Phosphatidylinositol 3-Kinases/metabolism MH - Phosphorylation MH - Rats MH - *Signal Transduction PMC - PMC3520983 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2012/12/20 06:00 MHDA- 2013/06/12 06:00 PMCR- 2012/12/12 CRDT- 2012/12/20 06:00 PHST- 2012/07/16 00:00 [received] PHST- 2012/11/01 00:00 [accepted] PHST- 2012/12/20 06:00 [entrez] PHST- 2012/12/20 06:00 [pubmed] PHST- 2013/06/12 06:00 [medline] PHST- 2012/12/12 00:00 [pmc-release] AID - PONE-D-12-20803 [pii] AID - 10.1371/journal.pone.0051294 [doi] PST - ppublish SO - PLoS One. 2012;7(12):e51294. doi: 10.1371/journal.pone.0051294. Epub 2012 Dec 12.