NTS-Polyplex: a potential nanocarrier for neurotrophic therapy of Parkinson's disease.

Unlabelled: Nanomedicine has focused on targeted neurotrophic gene delivery to the brain as a strategy to stop and reverse neurodegeneration in Parkinson's disease. Because of improved transfection ability, synthetic nanocarriers have become candidates for neurotrophic therapy. Neurotensin (NTS)-polyplex is a "Trojan horse" synthetic nanocarrier system that enters dopaminergic neurons through NTS receptor internalization to deliver a genetic cargo.

Heterogeneity in ventricular zone neural precursors contributes to neuronal fate diversity in the postnatal neocortex.

The recent discovery of short neural precursors (SNPs) in the murine neocortical ventricular zone (VZ) challenges the widely held view that radial glial cells (RGCs) are the sole occupants of this germinal compartment and suggests that precursor variety is an important factor of brain development. Here, we use in utero electroporation and genetic fate mapping to show that SNPs and RGCs cohabit the VZ but display different cell cycle kinetics and generate phenotypically different progeny. In addition, we find that RGC progeny undergo additional rounds of cell division as intermediate progenitor cells (IPCs), whereas SNP progeny generally produce postmitotic neurons directly from the VZ.

Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats.

Recently we showed that the neurotensin polyplex is a nanoparticle carrier system that targets reporter genes in nigral dopamine neurons in vivo. Herein, we report its first practical application in experimental parkinsonism, which consisted of transfecting dopamine neurons with the gene coding for human glial cell line-derived neurotrophic factor (hGDNF). Hemiparkinsonism was induced in rats by a single dose of 6-hydroxydopamine (30 microg) into the ventrolateral part of the striatum.

Postnatal cellular contributions of the hippocampus subventricular zone to the dentate gyrus, corpus callosum, fimbria, and cerebral cortex.

The rodent dentate gyrus (DG) is formed in the embryo when progenitor cells migrate from the dentate neuroepithelium to establish a germinal zone in the hilus and a secondary germinal matrix, near the fimbria, called the hippocampal subventricular zone (HSVZ). The developmental plasticity of progenitors within the HSVZ is not well understood. To delineate the migratory routes and fates of progenitors within this zone, we injected a replication-incompetent retrovirus, encoding the enhanced green fluorescent protein (EGFP), into the HSVZ of postnatal day 5 (P5) mice.

Biophysical characteristics of neurotensin polyplex for in vitro and in vivo gene transfection.

Previously we improved the neurotensin (NT)-polyplex by the coupling of HA2 fusogenic peptide (FP) and Vp1 SV40 karyophilic peptide (KP). We now report the proportion of [(125)I]-NT, [(3)H]-FP, and poly-l-lysine (PLL) in the NT-polyplex, and some of its biophysical properties. We concluded that the most efficient NT-polyplex comprised 1 NT, 4 FP, and 2 PLL molecules.

DNA damage and nonhomologous end joining in excitotoxicity: neuroprotective role of DNA-PKcs in kainic acid-induced seizures.

DNA repair plays a critical, but imprecisely defined role in excitotoxic injury and neuronal survival throughout adulthood. We utilized an excitotoxic injury model to compare the location and phenotype of degenerating neurons in mice (strain 129-C57BL) deficient in the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), an enzyme required for nonhomologous end joining (NHEJ). Brains from untreated adult heterozygous and DNA-PKcs null mice displayed comparable cytoarchitecture and undetectable levels of cell death.

Improved neurotensin-vector-mediated gene transfer by the coupling of hemagglutinin HA2 fusogenic peptide and Vp1 SV40 nuclear localization signal.

Recently we reported that neurotensin-SPDP-poly-L-lysine (NT-vector) is able to bind plasmid DNA (NT-polyplex) and polyfect cells expressing the high-affinity neurotensin receptor (NTRH) although with low transfecting efficiency: in vitro, 6.5+/-1.5%, and in vivo, 5+/-4%.