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Expression of beta-amyloid precursor protein mRNAs following transient focal ischaemia
J Koistinaho1, I Pyykönen, R Keinänen
1A.I. Virtanen Institute, University of Kuopio, Finland.
Abstract:
beta-Amyloid precursor protein (beta APP) can be alternatively processed to result in release of either neurotoxic amyloid beta-peptide, or secreted forms of beta APP, which might have a role in neuronal plasticity and survival. Four different forms of beta APP mRNAs have been described in rodents: APP695, APP714, APP751 and APP770. The two larger forms contain a Kunitz-type serine protease inhibitor domain (KPI). Since previous studies have shown increased APP immunoreactivity following brain ischaemia, we used in situ hybridization histochemistry to determine whether induction of any APP mRNA transcripts take place following focal brain ischaemia. While the hybridization signal of all APP isoforms in the infarct was lost 4-24 h following the insult, APP770 mRNA was slightly upregulated in the ipsilateral cortex and striatum 3 days after 90 min ischaemia. At 7 days post-ischaemia APP770 and APP751 mRNAs were induced in the infarct core and in a thin perifocal zone. KPI-containing APP forms are differentially induced following focal brain ischaemia, possibly as a neuroprotective response to neuronal injury.
Insights
This study investigated beta-amyloid precursor protein (beta APP) mRNA changes after brain ischemia. Certain beta APP forms containing a Kunitz-type protease inhibitor domain were upregulated, suggesting a neuroprotective role.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathology
Background:
- Beta-amyloid precursor protein (beta APP) processing yields neurotoxic amyloid beta-peptide or neuroprotective secreted forms.
- Four beta APP mRNA variants exist in rodents, with APP751 and APP770 containing a Kunitz-type protease inhibitor (KPI) domain.
- Previous research indicated increased APP immunoreactivity post-brain ischemia.
Purpose of the Study:
- To investigate the induction of different beta APP mRNA transcripts following focal brain ischemia using in situ hybridization histochemistry.
- To determine if KPI-containing beta APP forms are differentially regulated after ischemic injury.
Main Methods:
- Focal brain ischemia was induced in rodents.
- In situ hybridization histochemistry was employed to detect and quantify APP mRNA isoforms.
- Analysis was performed at 4-24 hours, 3 days, and 7 days post-ischemia.
Main Results:
- APP mRNA signals were lost in the infarct core within 4-24 hours post-insult.
- APP770 mRNA showed slight upregulation in the ipsilateral cortex and striatum at 3 days post-ischemia.
- APP770 and APP751 mRNAs (KPI-containing) were induced in the infarct core and perifocal zone at 7 days post-ischemia.
Conclusions:
- KPI-containing beta APP forms (APP751 and APP770) are differentially induced following focal brain ischemia.
- This induction may represent a neuroprotective response to neuronal injury.
- The findings highlight a potential role for specific beta APP isoforms in the brain's response to ischemic damage.