Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain

Jerzy Wegiel, Izabela Kuchna, Krzysztof Nowicki, Janusz Frackowiak, Karol Dowjat, Wayne P. Silverman, Barry Reisberg, Mony Deleon, Thomas Wisniewski, Tatyana Adayev, Mo Chou Chen-Hwang, Yu Wen Hwang

Research output: Contribution to journalArticle

Abstract

The minibrain kinase (Mnb/Dyrk1A) gene is localized in the Down syndrome (DS) critical region of chromosome 21. This gene encodes a proline-directed serine/threonine protein kinase (minibrain kinase-Mnb/Dyrk1A), which is required for the proliferation of distinct neuronal cell types during postembryonic neurogenesis. To study the distribution of Mnb/Dyrk1A during human brain development and aging, we raised Mnb/Dyrk1A-specific antibody (mAb 7F3) and examined 22 brains of normal subjects from 8 months to 90 years of age. We found that neurons were the only cells showing the presence of 7F3-positive product in both cell nucleus and cytoplasm. Nuclear localization supports the concept that Mnb/Dyrk1A may be involved in control of gene expression. Synaptic localization of Mnb/Dyrk1A also supports our previous studies suggesting that Mnb/Dyrk1A is a regulator of assembly of endocytic apparatus and appears to be involved in synaptic vesicle recycling and synaptic signal transmission. Accumulation of numerous 7F3-positive corpora amylacea in the memory and motor system subdivisions in subjects older than 33 years of age indicates that Mnb/Dyrk1A is colocalized with markers of astrocyte and neuron degeneration. Differences in the topography and the amount of Mnb/Dyrk1A in neurons, astrocytes, and ependymal and endothelial cells appear to reflect cell type- and brain structure-specific patterns in trafficking and utilization of Mnb/Dyrk1A.

Original languageEnglish (US)
Pages (from-to)69-80
Number of pages12
JournalBrain research
Volume1010
Issue number1-2
DOIs
StatePublished - Jun 4 2004

Keywords

  • Brain aging
  • Brain development
  • Cellular and molecular biology
  • Corpora amylacea
  • Immunocytochemistry
  • Minibrain kinase
  • Staining, tracing and imaging techniques
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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    Wegiel, J., Kuchna, I., Nowicki, K., Frackowiak, J., Dowjat, K., Silverman, W. P., Reisberg, B., Deleon, M., Wisniewski, T., Adayev, T., Chen-Hwang, M. C., & Hwang, Y. W. (2004). Cell type- and brain structure-specific patterns of distribution of minibrain kinase in human brain. Brain research, 1010(1-2), 69-80. https://doi.org/10.1016/j.brainres.2004.03.008