Background: Short-chain fatty acids (SCFAs) are metabolites produced by the gut microbiota after fiber fermentation. Some SCFAs, such as acetate, propionate, and butyrate, have been recognized as essential for human health, especially for the brain; however, the cellular mechanisms activated by these molecules in food-intake-related organs, such as the olfactory bulb, remain unclear. Objective: This study evaluates the effects of acetic acid (AA) and sodium butyrate on the physiology of Ca²⁺ metabolism in olfactory bulb cells (OBCs). Methods: Primary OBC cultures of the postnatal rat (P7-21) were made, and Ca²⁺ imaging experiments were performed to record the intracellular Ca²⁺ responses (iCaR) elicited by the application of AA and sodium butyrate (100 nM–1 mM). Immunocytochemical analyses were performed to identify GFAP⁺ cells and GPR41 and GPR43 receptors in OBCs. Endpoint RT-PCR analyses were made to identify GPR41 and GPR43 transcripts in OBCs. Results: Fewer than 10% of the OBCs tested responded to the application of AA and sodium butyrate with iCaR. Pharmacological studies (20 µM 2-aminoethyl diphenylborinate (2-APB); 10 nM GLPG0974, 120 nM AR420626) showed that iCaR were independent of inositol triphosphate (IP₃)-signaling pathways and that OBCs expressed both GPR41 and GPR43 receptors. Endpoint RT-PCR studies performed in both olfactory bulbs and primary OBC cultures confirmed the expression of the GPR41 receptor. Conclusions: This study shows that AA and butyrate induce intracellular Ca²⁺ responses activated by GPR41 and GPR43 receptors in a discrete cellular population of the rat olfactory bulb.

El glioblastoma multiforme es un tumor cerebral letal. Los esfuerzos experimentales realizados hasta hoy han mejorado nuestra comprensión sobre la fisiopatología de dicho tumor. Sin embargo, es necesario encontrar objetivos moleculares para identificar vulnerabilidades potenciales y abordar su patogénesis eficientemente. Este trabajo estudió tumores cerebrales de glioblastoma multiforme extirpados de dos pacientes. A través de registros de Ca2+ intracelular in situ e in vitro, RT-PCR de punto final y experimentos histológicos se caracterizó parcialmente el origen de las respuestas de Ca2+ intracelular en células de glioblastoma multiforme humano expuestos a diversas concentraciones extracelulares iónicas y de transmisores químicos. Con ello se encontró que el 70% de las células de glioblastoma multiforme generaron movimientos espontáneos de Ca2+ intracelular, entre los cuales aproximadamente el 9% mostró fluctuaciones rítmicas, incluso en ausencia de calcio y sodio extracelular. Además, los antagonistas de IP3R y SERCA no inhibieron completamente las respuestas de Ca2+ intracelular, mientras que los estudios de RT-PCR mostraron la expresión de S100A9, KCNH1, SLC12A5 y SLC8A1. Estos resultados sugieren la participación de estas proteínas como parte de la maquinaria de señalización celular del glioblastoma multiforme.

Classic non-homeostatic structures involved in food intake regulation are reciprocally influenced by metabolic signals. Orexigenic peptides expressed in the olfactory bulb (OB) and hippocampus (HP) modulate olfactory processing and memory, respectively. Hypothalamic circuits also modulate feeding behavior by activating and releasing Agouti-related peptide (AgRP) in response to orexigenic signals. An adequate response to fasting requires the expression of p75 neurotrophin receptor (p75NTR) in AgRP neurons. The present study aimed to determine whether there is a role for p75NTR and AgRP in the OB and HP on the feeding behavior of fasted rats. A group of fasted rats (FG) was confronted with a decision-making paradigm in a T-maze containing a standard chow pellet (CP), and the same pellet coated with a phenolic-rich avocado paste extract (AVO) on either end; their OB and HP were then analyzed with histological and molecular tools. FG rats had briefer feeding latencies, as compared to control rats fed ad libitum (median latencies: 55.4 vs 191.7 min, p = 0.032). They also had reduced cell counts in both brain structures, as compared to satiated rats. AgRP mRNA was not expressed in the HP of either group, however, it was found in the OB. p75NTR mRNA was expressed in both brain structures of FG rats. These results suggest that contrasting metabolic states (fasted or satiated) motivate different feeding responses, which are influenced by p75NTR and AgRP mRNA expression in non-homeostatic food intake brain structures.