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Induction of midkine expression in reactive astrocytes following rat transient forebrain ischemia
R Mochizuki1, A Takeda, N Sato
1Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Abstract:
Midkine (MK), a retinoic acid-responsive gene product, is a 13-kDa heparin-binding protein with neurotropic activity. Previous studies demonstrated the expression of MK in embryonal and neonatal brains and its potent neurotropic activities in vitro. Data concerning its role in the mature central nervous system, however, are still limited. We examined the changes of MK expression in the adult rat brain following transient forebrain ischemia, by Northern blot, in situ hybridization and immunohistochemical analyses. In the control brain, MK mRNA was expressed in the cortical and hippocampal neurons. Following the ischemia, up-regulation of MK mRNA and a corresponding increase of its protein products were found in the hippocampal CA1 subfield. The maximal expression was demonstrated on day 4 after the insult. The cells expressing MK were distributed around the depleted CA1 pyramidal cells and identified as reactive astrocytes by double immunostaining. These data suggest that MK may be an insult-induced molecule which participates in the reparative processes following neuronal injury.
Insights
Midkine (MK) expression increases in adult rat brains after ischemic injury. This protein, found in reactive astrocytes, may aid in repairing damaged neurons in the hippocampus.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Midkine (MK) is a heparin-binding protein with known neurotropic activities.
- Previous research established MK expression in developing brains, but its role in mature central nervous system injury is less understood.
Purpose of the Study:
- To investigate the expression patterns of Midkine (MK) in the adult rat brain following transient forebrain ischemia.
- To determine the cellular localization and temporal changes of MK following ischemic insult.
Main Methods:
- Northern blot analysis to detect MK mRNA levels.
- In situ hybridization to visualize MK mRNA distribution.
- Immunohistochemical analysis to identify MK protein expression and cellular localization, including double immunostaining for reactive astrocytes.
Main Results:
- MK mRNA and protein were constitutively expressed in cortical and hippocampal neurons of control adult rats.
- Transient forebrain ischemia induced significant up-regulation of MK mRNA and protein in the hippocampal CA1 subfield.
- Maximal MK expression was observed 4 days post-ischemia, with MK-expressing cells identified as reactive astrocytes surrounding damaged CA1 pyramidal neurons.
Conclusions:
- Midkine (MK) is an insult-induced molecule in the adult brain following ischemic injury.
- The up-regulation and localization of MK suggest its involvement in the reparative processes following neuronal damage, particularly in reactive astrocytes.