Experimental approaches to the study of primordial germ cell lineage and proliferation.

New information regarding primordial germ cell (PGC's) segregation and proliferation over the last decade is reviewed. Advances have been obtained in the mouse but current knowledge of human PGC's remains scant. Questions still fully or partially unresolved about the emergence of the germline in mammals are addressed. (i) When and where is the germ line set aside in the embryo? (ii) How is the germ line segregated from the somatic lineages? (iii) Which factors guide PGC's to the gonadal ridges? (iv) Which factors regulate PGC's proliferation? The main purpose of this review is to outline the information obtained using mainly in vitro culture systems about two aspects of these processes namely the segregation of PGC's and their proliferation.

Modulation of glutamate release and excitotoxicity by adenosine A2A receptors.

Because an increased glutamate outflow is thought to play a crucial role in triggering excitotoxic neuronal death, drugs able to regulate glutamate release could be effective for the management of neurodegenerative diseases. In this article, the authors discuss the hypothesis that adenosine A2A receptor antagonists (A2A antagonists) may belong to the aforementioned category. In rats bilaterally lesioned with the excitotoxin quinolinic acid (QA) in the striatum, the A2A antagonist SCH 58261 significantly reduced the motor, EEG, and neuropathologic changes induced by the lesion. Such effects of SCH 58261 occurred only at low doses and were paralleled by an inhibition of QA-stimulated glutamate release. The role played by A2A antagonists in the regulation of glutamate outflow was also confirmed by preliminary results obtained in the model of paired-pulse stimulation in corticostriatal slices. Conversely, based on data obtained in cultured striatal neurons, A2A antagonists appear unable to directly inhibit NMDA effects. In conclusion, A2A antagonists show clear neuroprotective effects in models of brain injury, although their actual therapeutic potential needs to be confirmed in a wider range of doses and in models of neurodegenerative diseases in which presynaptic and postsynaptic effects play different relative roles.