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ABSTRACT: An increasing number of observations suggests an important and complex role for both high- (tyrosine kinase receptor, trk) and low- (p75) affinity neurotrophin receptors (NTRs) during development in human brain. In the present study, the cell-specific distribution of NTRs was studied in different developmental lesions, including focal cortical dysplasia (FCD, n = 15), ganglioglioma (GG, n = 15) and dysembryoplastic neuroepithelial tumors, (DNT, n = 10), from patients with medically intractable epilepsy. Lesional, perilesional, as well as normal brain regions were examined for the expression of trkA, trkB, trkC and p75(NTR) by immunocytochemistry. In normal postmortem human cortex, immunoreactivity (IR) for trk and p75(NTR) was mainly observed in pyramidal neurons, whereas no notable glial IR was found within the white matter. All three trk receptors were encountered in high levels in the neuronal component of the majority of FCD, GG and DNT specimens. Strong trkA, trkB and trkC IR was found in neurons of different size, including large dysplastic neurons and balloon cells in FCD cases. In contrast, p75(NTR) IR was observed in only a small number of neuronal cells, which also contain trk receptors. Glial cells with astrocytic morphology showed predominantly IR for trkA in FCD and GG specimens, whereas oligodendroglial-like cells in DNT showed predominently IR for trkB. P75(NTR) IR was observed in a population of cells of the microglial/macrophage lineage in both FCD and glioneuronal tumors. Taken together, our findings indicate that the neuronal and the glial components of malformations of cortical development express both high- and low-affinity NTRs. Further research is necessary to investigate how activation of these specific receptors could contribute to the development and the epileptogenicity of these developmental disorders.
Acta Neuropathologica 12/2004; 108(5):422-34. · 9.32 Impact Factor
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Eleonora Aronica,
Jan A Gorter,
Marja Ramkema,
Sandra Redeker, Filiz Ozbas-Gerçeker,
Edwin A van Vliet,
George L Scheffer,
Rik J Scheper,
Paul van der Valk,
Johannes C Baayen,
Dirk Troost,
Filiz Ozbas-Gerçerer
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ABSTRACT: This study investigated the cellular distribution of different multidrug resistance (MDR)-related proteins such as P-glycoprotein (P-gp), the multidrug resistance-associated proteins (MRP) 1 and 2, and the major vault protein (MVP) in normal and sclerotic hippocampus of patients with medically refractory mesial temporal lobe epilepsy (MTLE).
Single- and double-label immunocytochemistry was used on brain sections of control hippocampus and of hippocampus of refractory MTLE patients.
In TLE cases with hippocampal sclerosis (HS), all four MDR proteins examined that had low or no expression in control tissue were upregulated, albeit with different cellular distribution patterns. P-gp immunoreactivity (IR) was observed in astrocytes in regions with diffuse reactive gliosis. In 75% of HS cases, strong P-gp IR was detected in blood vessels, with prominent endothelial labeling. Reactive astrocytes displayed low MRP1 IR. However, glial MRP1 expression was noted in glial endfoot processes around blood vessels. Neuronal MRP1 expression was observed in hypertrophic hilar neurons and in a few residual neurons of the CA1 region. Hippocampal MRP2 expression was observed in the large majority of HS cases in blood vessels. Hypertrophic hilar neurons and blood vessels within the sclerotic hippocampus expressed major vault protein (MVP).
These findings indicate that MDR proteins are upregulated in concert in the hippocampus of patients with refractory MTLE, supporting their role in the mechanisms underlying drug resistance. The specific cell-distribution patterns within the sclerotic hippocampus suggest different cellular functions, not necessarily linked only to clinical drug resistance.
Epilepsia 06/2004; 45(5):441-51. · 3.96 Impact Factor
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Pervin Dinçer,
Burcu Balci,
Yeliz Yuva,
Beril Talim,
Martin Brockington,
Deniz Dinçel,
Silvia Torelli,
Sue Brown,
Gülsev Kale,
Göknur Haliloglu, Filiz Ozbas Gerçeker,
Rengül Cetin Atalay,
Cengiz Yakicier,
Cheryl Longman,
Francesco Muntoni,
Haluk Topaloglu
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ABSTRACT: The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of alpha-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of alpha-dystroglycan.
Neuromuscular Disorders 01/2004; 13(10):771-8. · 2.80 Impact Factor
