Kaempferol protects against rat striatal degeneration induced by 3-nitropropionic acid.

3-Nitropropionic acid (NPA) produces degeneration of striatum and some neurological disturbances characteristic of Huntington's disease in rodents and primates. We have shown that the flavonoid kaempferol largely reduced striatal damage induced by cerebral ischaemia-reperfusion in rats (Lopez-Sanchez et al. 2007). In this work, we report that intraperitoneal (i.p.) administration of kaempferol affords an efficient protection against NPA-induced neurodegeneration in Wistar rats. We studied the effects of daily i.p. injections of 7, 14 and 21 mg of kaempferol/kg body weight during the NPA-treatment (25 mg/kg body weight/12 h i.p., for 5 days) on the neurological deficits, degeneration of rat striatum and oxidative stress markers. Intraperitoneal injections of 14-21 mg of kaempferol/kg body weight largely attenuated motor deficit and delayed mortality. The higher dose of kaempferol prevented the appearance of NPA-induced striatal lesions up to the end of treatment, as revealed by haematoxylin-eosin and TUNEL staining, and also NPA-induced oxidative stress, because it blocked the fall of reduced glutathione and the increase of protein nitrotyrosines in NPA-treated rats. It was found that striatal degeneration was associated with calpains activation and a large inactivation of creatine kinase, which were also prevented when the higher doses of kaempferol were administered.

Movement and commitment of primitive streak precardiac cells during cardiogenesis.

Fate maps are required to address questions about the commitment and differentiation of precardiac cells. Here, we report a detailed study of the precardiac cells located at the level of the primitive streak, employing different experiments with a variety of techniques combining double transplantations, microinjections and immunocytochemistry. Most cells of the more rostral segments of the primitive streak were found to contribute cells to the endodermal layer, adjacent to precardiac mesodermal cells of the heart forming region whose provenance was in the immediately more caudal segments of the primitive streak. We established a close spatio-temporal relationship between the two cell layers and the expression of their specific cardiac markers (cNkx-2.5, Bmp2, Cripto, Usmaar, dHand, GATA4, Pitx2, Hex, Fgf8, AMHC1 and VMHC1). We also analyzed the ability of precardiac cells to differentiate when they are transplanted to ectopic locations or are subjected to the influence of the organizer. We propose that the precardiac cells of the primitive streak form at least two groups with different significance. One, regulated by mediation of the organizer, is located preferentially in the more rostral region of the primitive streak. It consists of the prospective cells of the endoderm layer, with a hierarchic pattern of expression of different genes characterized by its capacity for induction and regulation of a second group of cells. This second group is located preferentially in the more caudal segments, and is fated to form the precardiac mesoderm, whose differentiation would be characterized by the expression of various specific genes.