RESUMEN
We have previously shown that chronic supplementation of taurine to mice significantly ameliorated the age-dependent decline in memory acquisition and retention. We also showed that concomitant with the amelioration in cognitive function, taurine caused significant alterations in the GABAergic and somatonergic system. These changes include increased levels of the neurotransmitters GABA and glutamate, increased expression of both isoforms of GAD and the neuropeptide somatostatin, decreased hippocampal expression of the beta (ß) 2/3 subunits of the GABA(A) receptor, an increase in the number of somatostatin-positive neurons, and an increase in the amplitude and duration of population spikes recorded from CA1 in response to Schaefer collateral stimulation and enhanced paired pulse facilitation in the hippocampus. These specific alterations of the inhibitory system caused by taurine treatment oppose those naturally induced by aging, suggesting a protective role of taurine in this process. In this study, we further investigated the effects of taurine on gene expression of relevant proteins of the inhibitory synapses using qRT-PCR method and found that taurine affects gene expression of various subunits of the GABA(A) receptors and GAD. Increased understanding the effects of taurine on gene expression will increase our understanding of age-related taurine-mediated neurochemical changes in the GABAergic system and will be important in elucidating the underpinnings of the functional changes of aging. Taurine might help forestall the age-related decline in cognitive functions through interaction with the GABAergic system.
Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Potenciales Postsinápticos Inhibidores/efectos de los fármacos , Potenciales Postsinápticos Inhibidores/genética , Taurina/administración & dosificación , Taurina/farmacología , Animales , Suplementos Dietéticos , Glutamato Descarboxilasa/genética , Glutamato Descarboxilasa/metabolismo , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genéticaRESUMEN
The molecular basis for odor perception in humans remains enigmatic because of the difficulty in studying odorant receptors (ORs) outside their native environment. Efforts toward OR expression and functional profiling have been met with limited success because of the poor efficiency of their cell surface expression in vitro. Structures protruding from the surface of olfactory sensory neurons called cilia contain all of the components of the olfactory signal transduction machinery and can be placed in an ex vivo plate assay to rapidly measure odor-specific responses. Here, we describe an approach using cilia isolated from the olfactory sensory neurons of mice expressing two human ORs, OR1A1 and OR5AN1, that showed 10- to 100-fold more sensitivity to ligands as compared to previous assays. A single mouse can produce enough olfactory cilia for up to 4000 384-well assay wells, and isolated cilia can be stored frozen and thus preserved. This pipeline offers a sensitive and highly scalable ex vivo odor-screening platform that has the potential to decode human olfaction.