Cerebellar Calcium-Binding Protein and Neurotrophin Receptor Defects in Down Syndrome and Alzheimer's Disease.

Cerebellar hypoplasia is a major characteristic of the Down syndrome (DS) brain. However, the consequences of trisomy upon cerebellar Purkinje cells (PC) and interneurons in DS are unclear. The present study performed a quantitative and qualitative analysis of cerebellar neurons immunostained with antibodies against calbindin D-28k (Calb), parvalbumin (Parv), and calretinin (Calr), phosphorylated and non-phosphorylated intermediate neurofilaments (SMI-34 and SMI-32), and high (TrkA) and low (p75NTR) affinity nerve growth factor (NGF) receptors as well as tau and amyloid in DS (n = 12), Alzheimer's disease (AD) (n = 10), and healthy non-dementia control (HC) (n = 8) cases. Our findings revealed higher Aß42 plaque load in DS compared to AD and HC but no differences in APP/Aß plaque load between HC, AD, and DS. The cerebellar cortex neither displayed Aß40 containing plaques nor pathologic phosphorylated tau in any of the cases examined. The number and optical density (OD) measurements of Calb immunoreactive (-ir) PC soma and dendrites were similar between groups, while the number of PCs positive for Parv and SMI-32 were significantly reduced in AD and DS compared to HC. By contrast, the number of SMI-34-ir PC dystrophic axonal swellings, termed torpedoes, was significantly greater in AD compared to DS. No differences in SMI-32- and Parv-ir PC OD measurements were observed between groups. Conversely, total number of Parv- (stellate/basket) and Calr (Lugaro, brush, and Golgi)-positive interneurons were significantly reduced in DS compared to AD and HC. A strong negative correlation was found between counts for Parv-ir interneurons, Calr-ir Golgi and brush cells, and Aß42 plaque load. Number of TrkA and p75NTR positive PCs were reduced in AD compared to HC. These findings suggest that disturbances in calcium binding proteins play a critical role in cerebellar neuronal dysfunction in adults with DS.

Expression of nerve growth factor receptors p75 in human bladder carcinoma and its influence by hypoxia / 中华泌尿外科杂志

Objective To explore the expression of the nerve growth factor receptors p75 (p75NGFR) in human bladder carcinoma samples, and the effects of hypoxia on the expression of p75NGFR in human bladder cancer ceils. Methods The expression of p75NGFR in 107 bladder cancer and lymph node specimens were immunohistochemically investigated. The expression of p75NGFR in bladder cancer cell line (T24) was assessed by immunocytochemistry, and reverse tran-scription-PCR in the Normoxic Condition (air, 5%CO2) and in hypoxia condition(10%O2, 5%CO2, 85%N2). Results p75NGFR expressed in 46 of 107(43.0%) tumor samples. There was no signifi-cant correlation between p75NGFR and the factors such as gender, age, extent of the tumors, and pathologic grading(P0.05), p75NGFR was expressed in examined cell line T24, and also expressed in 5 of 24 bladder tumors in metastasized lymph node specimens. Hypoxia markedly down-regulated the expression of p75NGFR of T24 cell line at third day. Conclusions It is suggested that p75NGFR is expressed less in lymph node metastasis. Hypoxia markedly inhibited expression of p75NGFR of T24 cell lines.