Zygmunt Galdzicki, Ph.D.
Associate Professor of Anatomy, Physiology and Genetics

University of Wroclaw, 1979; Academy of Medicine, Wroclaw, 1982
 
Research Interests:
Molecular and electrophysiological approach to understanding mental retardation in trisomy 21 - Down syndrome (DS)
 
The full trisomy 16 mouse (Ts16) is an animal model for DS with a triplication of the whole mouse chromosome 16. The distal portion of mouse chromosome 16 is homologous to nearly the entire long arm of human chromosome 21. Ts16 mice die in utero. At the beginning of the nineties a novel mouse model of DS the segmental trisomy Ts65Dn mouse was created. In this model only part of the chromosome 16 is triplicated and Ts65Dn mouse lives into adulthood. The extra chromosome contains all the genes in the DS critical region that are believed to be responsible for mental retardation. Behavioral and learning tests suggest dysfunction of the Ts65Dn hippocampus. Electrophysiological experiments demonstrate abnormal long-term potentiation and depression (models of learning and memory related to synaptic plasticity). In this laboratory we study signal transduction pathways and synaptic plasticity in Ts65Dn and other more recent DS mouse models using electrophysiological (patch-clamp, extracellular recording including multi-electrode array), optical and molecular techniques in order to understand the causes of impaired hippocampal function. To the extent that abnormalities in the trisomic mouse model of DS represent changes in the human DS brain, this research can give us new clues on the causes of mental retardation in DS and helps further to understand the plasticity of neuronal networks in general.
 
- Electrophysiological, pharmacological and molecular properties of glutamate receptors:
NMDA, AMPA, kainate and metabotropic receptors and their roles in neurodegenerative disorders and pain
 
Glutamate is a major excitatory neurotransmitter in the central nervous system and plays a principal function in hippocampal synaptic plasticity. Ionotropic glutamate receptors, NMDA and AMPA, are involved in long-term plasticity, whereas the role of the kainate and metabotropic receptors remains to be determined. There is a growing interest in glutamate receptor agonists and antagonists for use as neuroprotective and stimulating agents in a number of pathological conditions, including DS, Alzheimer disease, pain, Parkinson disease, multiple sclerosis, epilepsy, ischemia and schizophrenia. We study glutamate receptor subtype-specific agonists/antagonists that have potential therapeutic implication.
 
Alzheimer disease (AD), cholinergic vulnerability and neuronal-glia interactions
 
After 35 years of age, subjects with DS present severe AD-type neuropathology and frequently demonstrate dementia. The commonly accepted pathological markers for AD are an increase in the number of tangles containing abnormally phosphorylated tau and neuritic plaques containing beta-amyloid. Cholinergic neurons are particularly vulnerable in AD and in older DS individuals and cells in the nucleus basalis of Meynert are lost. The basis for neuronal degeneration in DS is still unknown. The most likely explanation for this is that the amyloid-precursor protein (APP) gene, a source of amyloid peptide, is triplicated in DS and in the animal models Ts16 and Ts65Dn, although mouse amyloid structure differs by three amino acids from human amyloid peptide. We use Ts65Dn and Ts16 models to study cholinergic deficit in DS and their implication in early onset of AD neuropathology in DS.
 
Recent Publications
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4301 Jones Bridge Road
Bethesda, Maryland 20814

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