Cation shifts as markers in neurodegenerative diseases: correlations with transmitter deficts in Alzheimer and Huntington disease and imaging of excitoxic brain damage

The clinical syndrome of dementia is best defined as an - usually at advanced age - acquired global impairment of intellect, memory and personality, but without impairment of consciousness, prominent causes of dementia are certain intrinsic degenerative diseases of the brain. The most common of these diseases is Alzheimer's disease (AD) . The pathological hallmark of AD is the presence of large amounts of so called plaques extracellular structures which involve processes of different neurons - and neurofibrillary tangles in nerve cell bodies of the cerebral cortex, hippocampus, amygdala and some subcortical brain areas.

Enhanced proliferation and dopaminergic differentiation of ventral mesencephalic precursor cells by synergistic effect of FGF2 and reduced oxygen tension

Effective numerical expansion of dopaminergic precursors might overcome the limited availability of transplantable cells in replacement strategies for Parkinson's disease. Here we investigated the effect of fibroblast growth factor-2 (FGF2) and FGF8 on expansion and dopaminergic differentiation of rat embryonic ventral mesencephalic neuroblasts cultured at high (20%) and low (3%) oxygen tension. More cells incorporated bromodeoxyuridine in cultures expanded at low as compared to high oxygen tension, and after 6 days of differentiation there were significantly more neuronal cells in low than in high oxygen cultures. Low oxygen during FGF2-mediated expansion resulted also in a significant increase in tyrosine hydroxylase-immunoreactive (TH-ir) dopaminergic neurons as compared to high oxygen tension, but no corresponding effect was observed for dopamine release into the culture medium. However, switching FGF2-expanded cultures from low to high oxygen tension during the last two days of differentiation significantly enhanced dopamine release and intracellular dopamine levels as compared to all other treatment groups. In addition, the short-term exposure to high oxygen enhanced in situ assessed TH enzyme activity, which may explain the elevated dopamine levels. Our findings demonstrate that modulation of oxygen tension is a recognizable factor for in vitro expansion and dopaminergic differentiation of rat embryonic midbrain precursor cells