RESUMO
The cellular prion protein (PrP(C)) has been implicated with the modulation of neuronal apoptosis, adhesion, neurite outgrowth and maintenance which are processes involved in the neocortical development. Malformations of cortical development (MCD) are frequently associated with neurological conditions including mental retardation, autism, and epilepsy. Here we investigated the behavioral performance of female adult PrP(C)-null mice (Prnp(0/0)) and their wild-type controls (Prnp(+/+)) presenting unilateral polymicrogyria, a MCD experimentally induced by neonatal freeze-lesion in the right hemisphere. Injured mice from both genotypes presented similar locomotor activity but Prnp(0/0) mice showed a tendency to increase anxiety-related responses when compared to Prnp(+/+) animals. Additionally, injured Prnp(0/0) mice have a poorer performance in the social recognition task than sham-operated and Prnp(+/+) injured ones. Moreover the step-down inhibitory avoidance task was not affected by the procedure or the genotype of the animals. These data suggest that the genetic deletion of PrP(C) confers increased susceptibility to short-term social memory deficits induced by neonatal freezing model of polymicrogyria in mice.
Assuntos
Transtornos Cognitivos/metabolismo , Transtornos da Memória/metabolismo , Neocórtex/anormalidades , Neurogênese/genética , Proteínas PrPC/genética , Animais , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/metabolismo , Transtornos de Ansiedade/fisiopatologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/fisiopatologia , Temperatura Baixa/efeitos adversos , Denervação , Modelos Animais de Doenças , Feminino , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/etiologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Transtornos da Memória/genética , Transtornos da Memória/fisiopatologia , Transtornos Mentais/genética , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Camundongos , Camundongos Knockout , Neocórtex/lesões , Neocórtex/fisiopatologiaRESUMO
In the present study, we tested the hypothesis that the ontogenetic development of the corpus callosum is relevant for the establishment of a normal neocortical structure. To that effect, neocortical morphology (thickness and neuronal density) was analyzed in adult Swiss mice rendered acallosal by midline transection at the first postnatal day (Acallosal group) and in non-manipulated mice. The neocortical thicknesses and neuronal densities of layers II+III through VI were measured in area 6 and at the 17/18a border, both of which present abundant callosal inputs, and in the relatively acallosal area 17. For the thickness measure, significant differences between Non-manipulated and Acallosal groups were only found in the areas that receive massive callosal connections. In area 6, Acallosal mice presented a reduced thickness of layer V, while at the 17/18a border, these mice presented a reduced thickness of layers II+III when compared to non-manipulated ones. No statistical difference between acallosal and non-manipulated mice was found regarding the neuronal density measure. The reduced cortical thickness associated with a comparatively normal neuronal density in neocortical regions which normally have abundant callosal connections suggest a reduction in the number of cortical neurons in acallosal mice. Altogether, the present data indicate that the input provided by callosal axons is necessary for the normal development of the neocortex.
Assuntos
Corpo Caloso , Neocórtex , Agenesia do Corpo Caloso , Animais , Animais Recém-Nascidos , Corpo Caloso/anatomia & histologia , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/cirurgia , Feminino , Humanos , Masculino , Camundongos , Neocórtex/anormalidades , Neocórtex/anatomia & histologia , Neocórtex/crescimento & desenvolvimento , Fatores SexuaisRESUMO
A previous study reported that adult mice irradiated at the 16th embryonic day present a severe neuronal number reduction in the dorsal lateral geniculate thalamic nucleus. In the present study, we investigated the time course of the effects of prenatal irradiation on this thalamic nucleus. One day after irradiation, a great number of pyknotic figures were seen mainly in the cerebral proliferative zones. In the geniculate nucleus, only scattered pyknotic figures were identified. On the first week after birth, the geniculate nucleus presented frequent pyknotic figures. From five days after birth onwards, a severe shrinkage of the occipital cortex and a great reduction in the geniculate nucleus neuronal number were found. On the second week after birth this neuronal number reduction reached as high as 75%. At each postnatal analyzed age, severe volumetric geniculate nucleus shrinkage was combined to non-significant neuronal density variations. The presence of few pyknotic figures in the geniculate nucleus one day after irradiation and its delayed neuronal loss indicate an indirect effect of irradiation. We suggest that the effect upon the geniculate nucleus is secondary to the damage of the occipital cortex. A possible interpretation for thalamic neuronal loss is that geniculate neurons fail to establish cortical arbors after major target loss. In this case, the loss of trophic support should also be considered.