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It has been shown that PP2A is critical for apoptosis in neural progenitor cells. However, it remains unknown whether PP2A is required for neuronal survival. To address this question, we generated forebrain-specific Ppp2cα knockout (KO) mice. We show that Ppp2cα KO mice display robust neuronal apoptosis and inflammatory responses in the postnatal cortex. Previous evidence has revealed that PD98059 is a potent ERK inhibitor and may protect the brain against cell death after cardiac arrest. To study whether PD98059 may have any effects on Ppp2cα KO mice, the latter was treated with this inhibitor. We demonstrated that the total number of cleaved caspase3 positive (+) cells in the cortex was significantly reduced in Ppp2cα KO mice treated with PD98059 compared with those without PD98059 treatment. We observed that the total number of IBA1+ cells in the cortex was significantly decreased in Ppp2cα KO mice treated with PD98059. Mechanistic analysis reveals that deletion of PP2Aca causes DNA damage, which may be attenuated by PD98059. Together, this study suggests that inhibition of ERK may be an effective strategy to reduce cell death in brain diseases with abnormal neuronal apoptosis.

There are few reports which were designed to compare the survival rate of human primary follicles with primordial follicles after cryopreservation. This study was designed to evaluate whether such a difference occurs. Human ovarian biopsies were cryopreserved using dimethylsulphoxide/sucrose as the cryoprotectants. Fresh and cryopreserved ovarian samples were evaluated for viability differences between the two types of follicles using the endpoints of histology, ultrastructure and DNA fragmentation. In comparison with fresh ovarian tissue (83.9% ± 10.0%), the percentage of morphologically normal primordial follicles was not significantly different in cryopreserved tissue (73.9% ± 17.2%). However, a lower percentage of primary follicles with normal morphology was seen in the cryopreserved group (43.3% ± 25.7% vs 74.8% ± 19.4% for the fresh group). Transmission electron microscopy revealed that the cryopreservation did not appear to affect the structural integrity of primordial follicles; however, varying ultrastructural damage to the cytoplasm was observed in the majority of the cryopreserved primary follicles. Using a DNA fragmentation assay, the percentage of apoptotic primordial and primary follicles in the unfrozen (26.3% and 20%) and frozen (23.3% and 25%) ovarian tissue was similar. A higher proportion of primary follicles, compared to primordial follicles, suffer histological damage after slow freezing.

The aim of the present study was to evaluate the effect of gonadotropins (Gn) on oocyte maturation, developmental competence and apoptosis in an animal model. Bovine cumulus–oocyte complexes (COCs) were matured for 24 h in media supplemented with varying concentrations of Bravelle (B), B + Menopur (B + M) or B + Repronex (B + R) (Ferring Pharmaceuticals, Parsiappany, NJ, USA). Then, nuclear maturation, embryo development, and apoptosis in cumulus cells and oocytes were evaluated. Low to moderate Gn concentrations (75–7500 mIU mL–1) effectively improved nuclear maturation and in vitro development. Higher concentrations of Gn (75 000 mIU mL–1) did not have any added beneficial effects and nuclear maturation and blastocyst rates in the presence of these concentrations were comparable to control (P > 0.05). Most COCs showed slight apoptosis when exposed to 75, 750 and 7500 mIU mL–1 Gn; however, when the concentration was increased to 75 000 mIU mL–1, the proportion of moderately apoptotic COCs increased. In conclusion, extremely high concentrations of Gn have detrimental effects on oocyte nuclear maturation and embryo development and increase apoptosis in cumulus cells, suggesting the importance of judicious use of Gn in assisted reproductive technologies (ART).