Genetic approaches identify adult pituitary stem cells.

Adult tissues undergo continuous cell turnover in response to stress, damage, or physiological demand. New differentiated cells are generated from dedicated or facultative stem cells or from self-renewing differentiated cells. Here we describe a different stem cell strategy for tissue maintenance, distinct from that observed for dedicated or facultative stem cells. We report the presence of nestin-expressing adult stem cells in the perilumenal region of the mature anterior pituitary and, using genetic inducible fate mapping, demonstrate that they serve to generate subsets of all six terminally differentiated endocrine cell types of the pituitary gland. These stem cells, while not playing a significant role in organogenesis, undergo postnatal expansion and start producing differentiated progeny, which colonize the organ that initially entirely consisted of differentiated cells derived from embryonic precursors. This generates a mosaic organ with two phenotypically similar subsets of endocrine cells that have different origins and different life histories. These parallel but distinct lineages of differentiated cells in the gland may help the maturing organism adapt to changes in the metabolic regulatory landscape.

Aluminum, restraint stress and aging: behavioral effects in rats after 1 and 2 years of aluminum exposure.

Both aluminum (Al) and aging have been associated with neurobehavioral changes in mammals. In this study, the long-lasting neurobehavioral effects of prenatal restraint stress and oral Al exposure from conception to sacrifice were assessed in adult (1 year) and old (2 years) rats. Pregnant females were orally exposed to 0, 50, and 100 mg Al/kg/day. Each Al-exposed group was divided into two subgroups. One of this was subjected to restraint stress (2h/day on gestation days 6-20). The offspring of the treated females were maintained with the same Al treatment until sacrifice at 1 or 2 years of age. Activity in an open-field and learning in a water maze were evaluated. Although no significant differences were observed in motor activity, a biphasic effect of Al on learning could be observed. Thus, exposure to 100 mg Al/kg decreased performance of the task in both adult and old rats when compared to animals exposed to 50 mg Al/kg. An age-related effect on water maze performance, as well as an accumulation of Al in brain of rats exposed to 100 mg Al/kg at 2 years of age was found. Interestingly, while prenatal restraint stress did not modify behavioral parameters, Al accumulation was prevented by prenatal restraint.

Concurrent exposure to aluminum and stress during pregnancy in rats: Effects on postnatal development and behavior of the offspring.

The present study was conducted to assess the potential combined influence of maternal restraint stress and aluminum (Al) exposure on postnatal development and behavior in the offspring of exposed rats. Female rats were concurrently exposed to 0 (control group), 50 or 100 mg/kg/day of Al administered as Al nitrate nonahydrate in drinking water with citric acid (355 or 710 mg/kg/day) for a period of 15 days prior to mating with untreated males. Aluminum exposure was maintained throughout the gestational, lactational and post-weaning periods. On days 6-20 of gestation, one-half of the pregnant animals in each group were restrained for 2 h/day. Food consumption and maternal body weight were decreased in the groups exposed to restraint only or combined with the highest Al dose. All of the animals were allowed to deliver and wean their offspring. The pups were evaluated for physical development and neuromotor maturation. Moreover, open-field activity, passive avoidance, and spatial learning in a water maze were also determined on postnatal days 30, 35 and 60, respectively. Body weight of pups treated with 100 mg/kg/day of Al was decreased relative to controls from postnatal day 12 through 21, sexual maturation was delayed in Al treated females and in males exposed to 100 mg/kg/day. Forelimb grip strength was reduced in males exposed to 100 mg/Al/kg/day and in females exposed to this Al dose plus prenatal restraint. Learning in a passive avoidance task indicated facilitated performance for Al treated rats at 100 mg/kg/day combined with prenatal restraint as evidenced by longer avoidance latencies, while learning in a water maze task showed a shorter latency to find the platform on acquisition day 2 for Al treated rats. However, no effects of Al on water maze performance were detected during the retention probe trial in which the only effect noted was an increase in the platform quadrant swim time for the prenatal restraint group. In general terms, the results of the present study did not show a notable influence of maternal restraint on the Al-induced postnatal developmental and behavioral effects in the offspring of prenatally Al-exposed rats.

Influence of age on aluminum-induced neurobehavioral effects and morphological changes in rat brain.

Aluminum (Al) is potentially toxic for mammals. In contrast to well documented Al neurotoxicity, neurobehavioral studies of Al in rodents have generally not produced robust or consistent results. In the present study, 16 young male (21 days old) and 16 old male (18 months) rats were exposed to 0 (control group) and 100 mg/kg/day of Al administered as Al nitrate nonahydrate in drinking water concurrently with citric acid (356 mg/kg/day) for a period of 100 days. At the end of the exposure period, rats were evaluated for motor activity in an open-field apparatus and learning in a passive avoidance test. After behavioral testing, rats were sacrificed and brain samples were collected to determine Al concentrations and to study synapses in the left CA1 fields of hippocampal formation. While no significant effects of Al exposure between groups could be detected on behavior, the total number of synapses decreased with age and Al exposure. In turn, the percentage of perforated synapses significantly increased in old Al-loaded rats.