RESUMO
The role of the cyclic nucleotide-gated (CNG) channel CNGA3 is well established in cone photoreceptors and guanylyl cyclase-D-expressing olfactory neurons. To assess a potential function of CNGA3 in the mouse amygdala and hippocampus, we examined synaptic plasticity and performed a comparative analysis of spatial learning, fear conditioning and step-down avoidance in wild-type mice and CNGA3 null mutants (CNGA3(-/-) ). CNGA3(-/-) mice showed normal basal synaptic transmission in the amygdala and the hippocampus. However, cornu Ammonis (CA1) hippocampal long-term potentiation (LTP) induced by a strong tetanus was significantly enhanced in CNGA3(-/-) mice as compared with their wild-type littermates. Unlike in the hippocampus, LTP was not significantly altered in the amygdala of CNGA3(-/-) mice. Enhanced hippocampal LTP did not coincide with changes in hippocampus-dependent learning, as both wild-type and mutant mice showed a similar performance in water maze tasks and contextual fear conditioning, except for a trend toward higher step-down latencies in a passive avoidance task. In contrast, CNGA3(-/-) mice showed markedly reduced freezing to the conditioned tone in the amygdala-dependent cued fear conditioning task. In conclusion, our study adds a new entry on the list of physiological functions of the CNGA3 channel. Despite the dissociation between physiological and behavioral parameters, our data describe a so far unrecognized role of CNGA3 in modulation of hippocampal plasticity and amygdala-dependent fear memory.
Assuntos
Comportamento Animal/fisiologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/fisiologia , Plasticidade Neuronal/genética , Plasticidade Neuronal/fisiologia , Sinapses/fisiologia , Estimulação Acústica , Tonsila do Cerebelo/metabolismo , Animais , Aprendizagem da Esquiva/fisiologia , Western Blotting , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Depressão/genética , Depressão/psicologia , Aprendizagem por Discriminação/fisiologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Medo/psicologia , Hipocampo/metabolismo , Imuno-Histoquímica , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reflexo de Sobressalto/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensação/fisiologia , Natação/psicologiaRESUMO
Cone dystrophies are genetic diseases characterized by loss of cone photoreceptor function and severe impairment of daylight vision. Loss of function is accompanied by a progressive degeneration of cones limiting potential therapeutic interventions. In this study we combined microarray-based gene-expression analysis with electroretinography and immunohistochemistry to characterize the pathological processes in the cone photoreceptor function loss 1 (cpfl1) mouse model. The cpfl1-mouse is a naturally arising mouse mutant with a loss-of-function mutation in the cone-specific Pde6c gene. Cpfl1-mice displayed normal rod-specific light responses while cone-specific responses were strongly diminished. Despite the lack of a general retinal degeneration, the cone-specific functional defect resulted in a marked activation of GFAP, a hallmark of Müller-cell gliosis. Microarray-based network-analysis confirmed activation of Müller-glia-specific transcripts. Unexpectedly, we found up-regulation of the cytokine LIF and the anti-apoptotic transcription factor STAT3 in cpfl1 cone photoreceptors. We postulate that STAT3-related pathways are induced in cpfl1 cone photoreceptors to counteract degeneration.
Assuntos
Regulação da Expressão Gênica , Células Fotorreceptoras Retinianas Cones/metabolismo , Degeneração Retiniana/genética , Fator de Transcrição STAT3/metabolismo , Animais , Camundongos , Camundongos Mutantes , Análise de Sequência com Séries de Oligonucleotídeos , Células Fotorreceptoras Retinianas Cones/patologia , Degeneração Retiniana/patologiaRESUMO
Functional and morphologic examinations of the feet of 100 sewing-machine-workers have been performed, and a comparison with a control group. The relative frequency of radiological changes was similar in both groups, most commonly on metatarso-phalangeal joints, on the tarsus and in the form of a spine of Achilles tendon. However, clinical and functional changes were significantly more often on the feet of sewing-machine-workers, which were perimalleolar oedema, metatarsalgia and hallux valgus. The changes are more often and serious parallelly to the age and duration of employment, they are more common on the forefoot, and markedly influence the working ability. Concerning the shape of foot, more changes were found on an "egyptian" than on a square foot. Summation of microtraumas and previous changes on the foot (before getting employed) contribute to the development of the found changes.