RESUMEN
Because of the importance of the HNK-1 carbohydrate for preferential motor reinnervation after injury of the femoral nerve in mammals, we screened NIH Clinical Collection 1 and 2 Libraries and a Natural Product library comprising small organic compounds for identification of pharmacologically useful reagents. The reason for this attempt was to obviate the difficult chemical synthesis of the HNK-1 carbohydrate and its isolation from natural sources, with the hope to render such compounds clinically useful. We identified six compounds that enhanced neurite outgrowth from cultured spinal motor neurons at nM concentrations and increased their neurite diameter, but not their neurite branch points. Axons of dorsal root ganglion neurons did not respond to these compounds, a feature that is in agreement with their biological role after injury. We refer to the positive functions of some of these compounds in animal models of injury and delineate the intracellular signaling responses elicited by application of compounds to cultured murine central nervous system neurons. Altogether, these results point to the potential of the HNK-1 carbohydrate mimetics in clinically-oriented settings.
Asunto(s)
Antígenos CD57/análogos & derivados , Ganglios Espinales/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Proyección Neuronal/efectos de los fármacos , Compuestos Orgánicos/farmacología , Animales , Células Cultivadas , Embrión de Mamíferos , Femenino , Ganglios Espinales/citología , Masculino , Ratones , Neuronas Motoras/citología , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológicoRESUMEN
BACKGROUND: Non-human primates, when encountering human beings, show wariness and alertness. These behaviors differ when there is direct human gaze vs. when human averts his gaze. METHODS: We observed cynomolgus monkey in their home cage and studied their behaviors in response to human gaze. Four behaviors were analyzed: opening mouth, staring at observer, agitated activity, and approaching observer. RESULTS: Three behaviors appeared to be sensitive to human gaze between when the human observer gazed at the monkey and when the human observer looked away. Individual animals also displayed subpatterns of responses to human gaze. CONCLUSIONS: These results indicate that, even in their home cage, monkeys display a heightened level of awareness when gazed upon by a human observer, suggesting that human gaze may elicit emotional reactions. Further, under the human gaze, distinct behavioral subpatterns were apparent within the monkey cohort in our study, indicative of subgroups within the cohort.