Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides.

The nucleic acid therapeutics field has made tremendous progress in the past decades. Continuous advances in chemistry and design have led to many successful clinical applications, eliciting even more interest from researchers including both academic groups and drug development companies. Many preclinical studies in the field focus on improving the delivery of antisense oligonucleotide drugs (ONDs) and/or assessing their efficacy in target tissues, often neglecting the evaluation of toxicity, at least in early phases of development.

Frequency of nuclear mutant huntingtin inclusion formation in neurons and glia is cell-type-specific.

Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder that is caused by a CAG expansion in the Huntingtin (HTT) gene, leading to HTT inclusion formation in the brain. The mutant huntingtin protein (mHTT) is ubiquitously expressed and therefore nuclear inclusions could be present in all brain cells. The effects of nuclear inclusion formation have been mainly studied in neurons, while the effect on glia has been comparatively disregarded.

Fetal porcine ventral mesencephalon graft. Determination of the optimal gestational age for implantation in parkinsonian patients.

Human fetal ventral mesencephalon tissue has been used as dopaminergic striatal implants in Parkinsonian patients, so far with variable effects. Fetuses from animals that breed in large litters, e.g.

Neurotrophic requirements of rat embryonic catecholaminergic neurons from the rostral ventrolateral medulla.

The factors that regulate the ontogeny and differentiation of C1 adrenergic neurons located in the rostral ventrolateral medulla (RVLM) are completely unknown. In the present study, we have investigated the effects of a number of neurotrophic factors on the survival of E18-19 rat C1 adrenergic neurons in culture. Immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) were used to study the expression of tyrosine hydroxylase (TH), an enzyme present in all catecholaminergic neurons, and of phenylethanolamine N-methyltransferase (PNMT), the final enzyme in the synthesis of adrenalin, as markers for the C1 RVLM neurons.

Fetal porcine ventral mesencephalon grafts: dissection procedure and cellular characterization in culture.

The objective of this study was to develop an optimal dissection procedure for fetal porcine ventral mesencephalon (VM) grafts and to characterize the cellular composition of such an explant, in particular with respect to the dopaminergic and GABAergic components. We have used a monolayer cell culture system to study and identify the various VM cell types. The in vitro development of the fetal VM cells and the effect of the addition of brain-derived neurotrophic factor (BDNF) was investigated during a culture period of 5 days.