03c417dd4c2b75996f61cf3235e72b1a nutrients-17-01851.pdf 3834e8b49f525ec5f795f2334255b89b08164758 nutrients-17-01851.pdf 07fd98c66ad9a6dcd2421235fca6e5c4188272c549972aef1cd0e837c8edef2c nutrients-17-01851.pdf Title: A Murine Model of High Dietary Histamine Intake: Impact on Histamine Contents and Release in Neural and Extraneural Tissues Subject: Background: Histamine intolerance, a disorder due to impaired degradation of dietary histamine, is frequently associated with headaches, but the underlying pathophysiology is largely unknown; the sensitization of meningeal afferents appears likely. We approached this issue by examining histamine concentrations in different tissues and meningeal histamine release in a new mouse model of high-histamine diets. Methods: C57BL/6 mice of both sexes were fed with diets containing 3 or 9 g/kg histamine and compared to control groups. After 10–30 days, the histamine concentration was determined in plasma, samples of homogenized ileum, trigeminal ganglia, spinal medulla, and cerebellum using an ELISA. The histamine release from mast cells in the dura mater stimulated with compound 48/80 was also examined. Results: Animals supplied with high dietary histamine showed normal behavior and no signs of suffering. Compared with the controls, the histamine concentration was significantly higher in plasma and ileum of mice fed with 3 g/kg, highest in animals fed with 9 g/kg histamine. In addition, this group of animals showed also higher histamine concentrations in the trigeminal ganglion. The histamine release from the dura mater in mice supplied with 3 g/kg histamine was not significantly different to control animals, but the relative increase in stimulated release was lower in male animals of the high histamine group. Conclusions: High dietary histamine increases histamine levels in blood plasma and the gut, whereas the histamine content of neural tissues is not significantly influenced. The lowered stimulated release in animals subjected to high dietary histamine may indicate compensatory mechanisms. Keywords: histamine intolerance; dietary histamine; plasma histamine; histamine release; mast cells; trigeminal system; mouse Author: Annette Kuhn, Jana Schramm, Birgit Vogler, Mária Dux, Fernando de Mora and Karl Messlinger Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Thu May 29 11:08:17 2025 CEST ModDate: Thu May 29 11:11:58 2025 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4899216 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- UZPSBC+URWPalladioL-Roma Type 1 Custom yes yes yes 10 0 KRVANX+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 YTHFRD+URWPalladioL-Ital Type 1 Custom yes yes yes 21 0 QMDDXF+CMSY10 Type 1 Builtin yes yes yes 47 0 URYLRZ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 55 0 PEFEGC+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 65 0 PEFEGE+PalatinoLinotype TrueType WinAnsi yes yes no 68 0 OVNEXW+EURM10 Type 1 Builtin yes yes yes 78 0 PEFEGE+PalatinoLinotype TrueType WinAnsi yes yes no 94 0 PEFEGG+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 97 0 PEFFAF+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 100 0 PEFEGE+PalatinoLinotype TrueType WinAnsi yes yes no 114 0 PEFEGE+PalatinoLinotype TrueType WinAnsi yes yes no 129 0 PEFEGE+PalatinoLinotype TrueType WinAnsi yes yes no 147 0 PEFEGE+PalatinoLinotype TrueType WinAnsi yes yes no 159 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-09-17 03:09:37 CEST RepresentationInformation: nutrients-17-01851.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-09-16 14:38:08 CEST Size: 4899216 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 312 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Animals and Ethics Destination: subsection.2.1 Item: Title: Low and High Dietary Histamine Fed Mice Destination: subsection.2.2 Item: Title: Tissue Sample Preparation Destination: subsection.2.3 Item: Title: Histamine Release Experiments Destination: subsection.2.4 Item: Title: Histamine Concentration Assessment Destination: subsection.2.5 Item: Title: Toluidine Blue Staining of Dura Mater Destination: subsection.2.6 Item: Title: Calculations and Statistics Destination: subsection.2.7 Item: Title: Results Destination: section.3 Children: Item: Title: Condition, Food Consumption, and Changes in Body Weight Destination: subsection.3.1 Children: Item: Title: Animals Supplied with Altromin for 3 4 Weeks Destination: subsubsection.3.1.1 Item: Title: Animals Supplied with Ssniff for About 3 Weeks Destination: subsubsection.3.1.2 Item: Title: Histamine Content of Blood Plasma, Ileum, Trigeminal Ganglia, and Cerebellum Destination: subsection.3.2 Item: Title: Histamine Release from Mouse Dura Mater Destination: subsection.3.3 Item: Title: Toluidine Blue Staining of Mast Cells in Mouse Dura Mater Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Children: Item: Title: Impact of High Histamine on Animal Conditions Destination: subsection.4.1 Item: Title: Histamine Levels in Different Tissues Destination: subsection.4.2 Item: Title: Histamine Uptake into Tissues Destination: subsection.4.3 Item: Title: Mast Cells in the Dura Mater Destination: subsection.4.4 Item: Title: Histamine Release from the Dura Mater Destination: subsection.4.5 Item: Title: Limitations and Future Perspectives Destination: subsection.4.6 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: A Murine Model of High Dietary Histamine Intake: Impact on Histamine Contents and Release in Neural and Extraneural Tissues Author: Annette Kuhn, Jana Schramm, Birgit Vogler, Mária Dux, Fernando de Mora and Karl Messlinger Subject: Background: Histamine intolerance, a disorder due to impaired degradation of dietary histamine, is frequently associated with headaches, but the underlying pathophysiology is largely unknown; the sensitization of meningeal afferents appears likely. We approached this issue by examining histamine concentrations in different tissues and meningeal histamine release in a new mouse model of high-histamine diets. Methods: C57BL/6 mice of both sexes were fed with diets containing 3 or 9 g/kg histamine and compared to control groups. After 10 30 days, the histamine concentration was determined in plasma, samples of homogenized ileum, trigeminal ganglia, spinal medulla, and cerebellum using an ELISA. The histamine release from mast cells in the dura mater stimulated with compound 48/80 was also examined. Results: Animals supplied with high dietary histamine showed normal behavior and no signs of suffering. Compared with the controls, the histamine concentration was significantly higher in plasma and ileum of mice fed with 3 g/kg, highest in animals fed with 9 g/kg histamine. In addition, this group of animals showed also higher histamine concentrations in the trigeminal ganglion. The histamine release from the dura mater in mice supplied with 3 g/kg histamine was not significantly different to control animals, but the relative increase in stimulated release was lower in male animals of the high histamine group. Conclusions: High dietary histamine increases histamine levels in blood plasma and the gut, whereas the histamine content of neural tissues is not significantly influenced. The lowered stimulated release in animals subjected to high dietary histamine may indicate compensatory mechanisms. 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