RESUMO
Aging is accompanied by poor learning and memory abilities and by decreased hippocampal neurogenesis, a process that is also modulated by oxidative stress (OS). P66(Shc) has recently emerged as a novel mammalian gerontogene able to affect healthspan during aging. Deletion of this gene in mice leads to reduced OS accompanied by decreased incidence of age-related pathologies and reduced signs of behavioral aging. We hypothesized that p66(Shc-/-) mutants might show increased neurogenesis in the hippocampus, a brain region involved in learning and memory processes. To this aim, granule cell number, proliferation, neuronal differentiation, and cell death were assessed in the hippocampus in senescent p66(Shc-/-) [knock out (KO)] and p66(Shc+/+) [wild type (WT)] male and female mice. Spatial learning abilities and spontaneous activity were also investigated in a multifunctional behavioral system-IntelliCages. The behavioral analysis revealed that females in general perform better in spatial learning tasks, with genotype effects being apparent in the activity pattern only. Likewise, all females showed increased neuronal differentiation, whereas increased proliferation was found only in those belonging to the p66(Shc-/-) genotype, indicating that they might be protected from precursor cell loss. The number of dying cells was not affected by genotype or sex; however, all KO mice showed less granule cells than WT. Overall, our data suggest that hippocampal function is protected in the female gender at older age, an effect amplified by reduced OS in the p66(Shc-/-) mutant.
Assuntos
Envelhecimento/fisiologia , Hipocampo/fisiologia , Neurogênese/fisiologia , Caracteres Sexuais , Proteínas Adaptadoras da Sinalização Shc/genética , Animais , Morte Celular/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células , Feminino , Imuno-Histoquímica , Aprendizagem/fisiologia , Masculino , Camundongos , Camundongos Knockout , Modelos Animais , Neurônios/citologia , Neurônios/fisiologia , Estresse Oxidativo/fisiologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de SrcAssuntos
Envelhecimento/patologia , Faringe/patologia , Faringe/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Idoso , Envelhecimento/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos Faríngeos/fisiopatologia , Polissonografia , Apneia Obstrutiva do Sono/patologiaRESUMO
The role for Pax7 in establishing tectal polarity and map refinement was authenticated by gene expression studies in vivo and in vitro. Throughout development (stages E2-E12 were examined) a rostral(low)-caudal(high) and dorsal(high)-ventral(low) Pax7 expression gradient was detected immunohistochemically in the chick optic tectum, indicating a role for Pax7 in establishing tectal polarity. Chick retino-recipient tectal cells positive for Pax7 also co-expressed ephrin-A2, a molecule involved in the establishment and refinement of the retinotopic map. In vitro, PAX7 up-regulated ephrin-A2 when transfected into undifferentiated P19 cells; cells became negative for both Pax7 and ephrin-A2 protein following treatment with anti-sense oligonucleotides. These results suggest that in addition to being involved in the early establishment of tectal polarity, Pax7 plays a later role in retino-tectal map formation and refinement.
