Nerve Cell Damage and Neuroprotection in the Developing Brain
Project description: The purpose of our research is to clarify molecular processes involved in receptor-mediated nerve cell death, neurogenesis, and synaptic plasticity, and to study the effectiveness of proposed neuroprotective drugs in ameliorating the damage in the developing brain. Better understanding of tho complex mechanisms involved in nerve cell death, and on the other hand, neurogenesis, in the immature, plastic brain will offer targets for potential therapeutic interventions to treat pediatric patients suffering from such diseases as epilepsy, hypoxic-ischemic and post traumatic brain damage. Our research is focused on the hippocampus - the structure of great vulnerability, and of major importance in learning and memory.
Current topics: Current research in the developing hippocampus is focused on the following topics:
- GABA Areceptor-mediated regulation of neuronal plasticity
- Signaling pathways involved in nerve cell death
- Role of inflammation in nerve cell death and epileptogenesis
- Seizure-induced neurogenesis
Methods used:
- Organotypic hippocampal slice cultures and primary nerve cell and astroglial cultures
- Animal models of epilepsy in rats and mic
- Protein chemistry and proteomics, molecular biology, gene array technolog
- Immunohistochemistry, different staining methods
- Microscopy techniques including confocal and electron microscopy¨
- Proteomics; collaboration with the Unit of Proteomics
Selected recent publications:
Laurén HB, Lopez-Picon FR, Brandt A, Rios-Rojas C, Holopainen IE. 2010. Transcriptome analysis of the hippocampal CA1 pyramidal cell region after kainic acid-induced status epilepticus in juvenile rats. PLoS ONE, 5(5), e10733, 1-15.
Holopainen IE. 2008. Seizures in the developing brain: Cellular and molecular mechanisms of neuronal damage, neurogenesis and cellular reorganization. Review. Neurochem. Int. 52, 935-947.
Järvelä J, Lopez-Picon FR, Holopainen IE. 2008. Age-dependent cyclooxygenase-2 induction and neuronal damage after status epilepticus in the postnatal rat hippocampus. Epilepsia, 49, 832-841.
Laurén HB, Lopez-Picon FR, Kukko-Lukjanov T-K, Uusi-Oukari M, Holopainen IE. 2007. Status epilepticus alters zolpidem sensitivity of [3H]flunitrazepam binding in the developing rat brain. Neuroscience 146, 802-811.
Kukko-Lukjanov T-K, Soini S, Taira T, Michelsen KA, Panula P, Holopainen IE. 2006. Histaminergic neurons protect the developing hippocampus from kainic acid-induced neuronal damage in organotypic co-culture system. J Neurosci, 25, 1088-1097.
Holopainen IE. 2005. Organotypic hippocampal slice cultures: A model system to study basic cellular and molecular mechanisms of neuronal cell death, neuroprotection, and synaptic plasticity. Neurochem Res, 30, 1521-1528.
Laurén HB, Lopez-Picon FL, Korpi ER, Holopainen IE. 2005. Kainic acid-induced status epilepticus alters GABAA–receptor subunit mRNA and protein expression in the developing rat hippocampus. J Neurochem. 94:1384-1394.
Holopainen IE, Lauren HB. 2003. Neuronal activity regulates GABAA receptor subunit expression in organotypic hippocampal slice cultures. Neuroscience 118: 967-974.
Lopez-Picon FR, Uusi-Oukari M, Holopainen IE. 2003. Differential expression and localization of the phosphorylated and nonphosphorylated neurofilaments during the early postnatal development of rat hippocampus. Hippocampus 13: 767-779.
Research group: (e mail address):
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- Irma Holopainen, Principal investigator, MD, PhD; phone: + 358-2-333 7018 (irma.holopainen@utu.fi)
- Hanna Lauren, Ph.D. (hlauren@utu.fi)
- Juha Järvelä, Med.Lic. (juha.jarvela@utu.fi)
Graduate students:
- Olli Kannaste, B.Sc. (olli.kannaste@utu.fi)
- Anna Plysjuk, B. Med. (anna.plysjuk@utu.fi)
- Maria Grönman, B. Sc. (maria.gronman@utu.fi)
- Jenni Virta, B. Sc. (jevirt@utu.fi)