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.
Cortical dysplasias are malformations of cortical development characterized by disorganization of the cyto- and myeloarchitecture of the neocortex. They are a common cause of epilepsy and their diagnosis through conventional imaging can often be challenging, hindering surgical treatments. Diffusion-weighted magnetic resonance imaging (dMRI) has the ability to infer tissue properties at the microscopic scale, making it a promising technique for detection of cortical dysplasias. This study aims to assess the microarchitecture of the cerebral cortex in a murine model of cortical dysplasia using dMRI acquired with b-tensor encoding. Pregnant Sprague-Dawley rats were administered either carmustine (BCNU) or saline solution on day 15 of gestation. Their offspring were imaged at 120 days of age using a 7 tesla scanner, acquiring diffusion-sensitive images with b-tensor encoding. Images were processed with Q-space trajectory imaging with positivity constraints (QTI+) to derive various metrics along a curvilinear coordinate system across the neocortex. After scanning, the brains were processed for immunofluorescence and histological examinations. Experimental animals exhibited a significant reduction of microscopic fractional anisotropy (µFA) and anisotropic kurtosis (K shear ) in the middle and lateral cortical layers compared to the control animals. Immunofluorescence and histological analysis showed decreased and dysorganized myelinated fibers, and an increase of glial processes in BCNU-treated animals. Given the applicability of b-tensor encoding in clinical scanners, this approach holds promise for improving detection of focal cortical dysplasias in patients with epilepsy.
Cortical dysplasias are malformations of cortical development characterized by disorganization of the cyto- and myeloarchitecture of the neocortex. They are a common cause of epilepsy and their diagnosis through conventional imaging can often be challenging, hindering surgical treatments. Diffusion-weighted magnetic resonance imaging (dMRI) has the ability to infer tissue properties at the microscopic scale, making it a promising technique for detection of cortical dysplasias. This study aims to assess the microarchitecture of the cerebral cortex in a murine model of cortical dysplasia using diffusion-weighted magnetic resonance imaging (dMRI) acquired with b-tensor encoding. Pregnant Sprague-Dawley rats were administered either carmustine (BCNU) or saline solution on day 15 of gestation. Their offspring were imaged at 120 days of age using a 7 tesla scanner, acquiring diffusion-sensitive images with b-tensor encoding. Images were processed with Q-space trajectory imaging with positivity constraints (QTI+) to derive various metrics along a curvilinear coordinate system across the neocortex. After scanning, the brains were processed for immunofluorescence and histological examinations. Experimental animals exhibited a significant reduction of microscopic fractional anisotropy (µFA) and anisotropic kurtosis (Ka) in the middle and lateral cortical layers compared to the control animals. Immunofluorescence and histological analysis showed decreased and dysorganized myelinated fibers, and an increase of glial processes in BCNU-treated animals. Given the applicability of b-tensor encoding in clinical scanners, this approach holds promise for improving detection of focal cortical dysplasias in patients with epilepsy.