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The application of sodium cyanide (NaCN) to the carotid body receptors (CBR) (CBR stimulation) induces rapid blood hyperglycemia and an increase in brain glucose retention. The commissural nucleus tractus solitarius (cNTS) is an essential relay nucleus in this hyperglycemic reflex; it receives glutamatergic afferents (that also release brain derived neurotrophic factor, BDNF) from the nodose-petrosal ganglia that relays CBR information. Previous work showed that AMPA in NTS blocks hyperglycemia and brain glucose retention after CBR stimulation. In contrast, BDNF, which attenuates glutamatergic AMPA currents in NTS, enhances these glycemic responses. Here we investigated the combined effects of BDNF and AMPA (and their antagonists) in NTS on the glycemic responses to CBR stimulation. Microinjections of BDNF plus AMPA into the cNTS before CBR stimulation in anesthetized rats, induced blood hyperglycemia and an increase in brain arteriovenous (a-v) of blood glucose concentration difference, which we infer is due to increased brain glucose retention. By contrast, the microinjection of the TrkB antagonist K252a plus AMPA abolished the glycemic responses to CBR stimulation similar to what is observed after AMPA pretreatments. In BDNF plus AMPA microinjections preceding CBR stimulation, the number of c-fos immunoreactive cNTS neurons increased. In contrast, in the rats microinjected with K252a plus AMPA in NTS, before CBR stimulation, c-fos expression in cNTS decreased. The expression of AMPA receptors GluR2/3 did not change in any of the studied groups. These results indicate that BDNF in cNTS plays a key role in the modulation of the hyperglycemic reflex initiated by CBR stimulation. [ABSTRACT FROM AUTHOR]

Abstract: It is well-known that increased lipid peroxidation and failure of antioxidant mechanisms leads to neuronal damage in schizophrenic patients. However, this neurodegenerative mechanism has not been studied in treatment refractory schizophrenics (TRS). Therefore, the main purpose of this study was to determine neuronal damage in TRS in comparison to non-refractory schizophrenics (NRS) by means of quantitative analysis of lipid peroxidation and neuron specific enolase (NSE) related to the psychopathology severity. Two groups of paranoid schizophrenics, TRS and NRS, and a group of healthy controls (CO) were assembled (n =13). Lipid peroxidation was analyzed through spectrophotometry for quantification of malonaldehyde (MDA) and 4-hydroxynonenal (4-HNE) serum concentrations. As well, serum NSE was quantified by radioimmunoassay (ELSA). Psychopathology was evaluated using the brief psychiatric rating scale (BPRS) and the positive and negative symptoms scale (PANSS). TRS showed significant higher concentrations of lipoperoxides by-products and NSE, than NRS and CO. Clinical scores also revealed a more severe pathology in TRS, than in NRS. Raised lipoperoxidation correlated with higher delusions and emotional withdrawal symptoms, and increased NSE correlated with a lower flow of the conversation and lack of spontaneity. All these results together suggest that TRS patients suffer a greater lipid peroxidation and neuronal damage than NRS, apparently related to worsening of some of the psychiatric symptoms. [Copyright &y& Elsevier]