Cochlear glial cells mediate glutamate uptake through a sodium-independent transporter.

Since glutamate is the primary excitatory neurotransmitter in the mammalian cochlea, the mechanisms for the removal of glutamate from the synaptic and extrasynaptic spaces are critical for maintaining normal function of this region. Glial cells of inner ear are crucial for regulation of synaptic transmission throughout since it closely interacts with neurons along the entire auditory pathway, however little is known about the activity and expression of glutamate transporters in the cochlea. In this study, using primary cochlear glial cells cultures obtained from newborn Balb/C mice, we determined the activity of a sodium-dependent and sodium-independent glutamate uptake mechanisms by means of High Performance Liquid Chromatography. The sodium-independent glutamate transport has a prominent contribution in cochlear glial cells which is similar to what has been demonstrated in other sensory organs, but it is not found in tissues less susceptible to continuous glutamate-mediated injuries. Our results showed that xCG- system is expressed in CGCs and is the main responsible for sodium-independent glutamate uptake. The identification and characterization of the xCG- transporter in the cochlea suggests a possible role of this transporter in the control of extracellular glutamate concentrations and regulation of redox state, that may aid in the preservation of auditory function.

Putative Activation of Cannabinoid Receptor Type 1 Prevents Brain Oxidative Stress and Inhibits Aggressive-Like Behavior in Zebrafish.

Background: Aggression is a set of complex behaviors commonly described in different neurological disorders, such as schizophrenia, autistim spectrum disorder, and anxiety. Previous studies have described that some changes in the redox status of the brain are closely associated with aggressive behavior in different species. In addition, the endocannabinoid system acts as a neuromodulator of the central nervous system, however, its participation in aggressive behavior needs to be elucidated. Danio rerio (zebrafish) is an important model in the study of aggression, in this context, the present study investigated whether the activation of type 1 cannabinoid receptors (CB1r) alters the cerebral redox state and aggressive behavior in zebrafish. Materials and Methods: We performed pharmacological manipulations with the CB1r agonist (ACEA) and antagonist (AM-251) to assess the role of this receptor in aggressive behavior. Individuals were isolated in pairs, without physical contact for 24 h, treated with the drugs of interest, and after 30 minutes of pharmacokinetics, the fights were filmed for 30 min, and the individuals were identified as dominant or subordinate. Results: A consistent decrease in the strike and bite aggressive behavior was observed in the group treated with the ACEA agonist compared with that in the control and AM-251 groups. When evaluating the cerebral redox state, we observed that treatment with the ACEA agonist reduced malondialdehyde (MDA) levels and increased the levels of sulfhydryl groups compared with those in the control group. These results indicate that the activation of CB1r by the ACEA agonist inhibited aggressiveness and attenuated the levels of oxidative stress in both subjects (dominant or subordinate) in the treated group. Conclusion: Thus, we suggest that zebrafish is an alternative model to study common aggressive behavior disorders among species and that CB1r represent a potential target for the development of treatments for aggressive disorders.