Combining Gene Transfer and Nonhuman Primates to Better Understand and Treat Parkinson's Disease.

Parkinson's disease (PD) is a progressive CNS disorder that is primarily associated with impaired movement. PD develops over decades and is linked to the gradual loss of dopamine delivery to the striatum, the loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). While the administration of L-dopa and deep brain stimulation are potent therapies, their costs, side effects and gradual loss of efficacy underlines the need to develop other approaches.

Lessons from the analysis of nonhuman primates for understanding human aging and neurodegenerative diseases.

Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates.

[The diversity of aging models].

Most of the signalling pathways involved in aging regulation have been recently found well conserved at various levels throughout the evolution. Taking this into account, a diversity of model organisms, including worms, rodents, and lemurs as well, allows to address different questions: how to understand the interactions between genetic and environmental factors while challenging theories of aging, to preserve hearing integrity, to fight against senescence of neural stem cells, or to explore brain fitness from gene expression to cognitive and social behavior? Here are the main issues that can be considered, stressing the complementarities of the models. The differentiation of aging physiological aspects from those induced by age-related pathologies will also be specified.

Discovering novelty in sequential patterns: application for analysis of microarray data on Alzheimer disease.

Unlabelled: Analyzing microarrays data is still a great challenge since existing methods produce huge amounts of useless results. We propose a new method called NoDisco for discovering novelties in gene sequences obtained by applying data-mining techniques to microarray data.

Method: We identify popular genes, which are often cited in the literature, and innovative genes, which are linked to the popular genes in the sequences but are not mentioned in the literature.

GeneMining: identification, visualization, and interpretation of brain ageing signatures.

Transcriptomic technologies are promising tools for identifying new genes involved in cerebral ageing or in neurodegenerative diseases such as Alzheimer's disease. These technologies produce massive biological data, which so far are extremely difficult to exploit. In this context, we propose GeneMining, a multidisciplinary methodology, which aims at developing new strategies to analyse such data, and to design interactive tools to help biologists to identify, visualize and interpret brain ageing signatures.

Expression of glutamate transporters in the medial and lateral vestibular nuclei during rat postnatal development.

The postnatal developmental expression and the distribution of the glutamate transporters (GLAST, GLT-1 and EAAC1) were analyzed in rat vestibular nuclei (VN), at birth and during the following 4 weeks. Analyses were performed using reverse transcriptase-polymerase chain reaction and immunoblotting of GLAST, GLT-1 and EAAC1 mRNA and protein during the postnatal development of the VN neurons and their afferent connections. We also studied the distribution of each glutamate transporter in the medial and lateral VN by use of immunocytochemistry and confocal microscopy.

Calcium-binding proteins map the postnatal development of rat vestibular nuclei and their vestibular and cerebellar projections.

We investigated whether three calcium-binding proteins, calretinin, parvalbumin, and calbindin, could identify specific aspects of the postnatal development of the rat lateral (LVN) and medial (MVN) vestibular nuclei and their vestibular and cerebellar connections. Calretinin levels in the vestibular nuclei, increased significantly between birth and postnatal day (P) 45. In situ hybridization and immunocytochemical staining showed that calretinin-immunoreactive neurons were mostly located in the parvocellular MVN at birth and that somatic and dendritic growth occurred between birth and P14.