Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder
Elevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the histamine−2 receptors in parietal cells, thereb...
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2023-02-01
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| author | Divya Bharathi Selvaraj Jemi Feiona Vergil Andrews Muthuswamy Anusuyadevi Mahesh Kandasamy |
| author_facet | Divya Bharathi Selvaraj Jemi Feiona Vergil Andrews Muthuswamy Anusuyadevi Mahesh Kandasamy |
| author_sort | Divya Bharathi Selvaraj |
| collection | DOAJ |
| description | Elevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the histamine−2 receptors in parietal cells, thereby reducing the production of HCl in the stomach. While some reports indicate the neuroprotective effects of ranitidine, its role against GI disorder-related anxiety remains unclear. Therefore, we investigated the effect of ranitidine against anxiety-related behaviors in association with changes in neuronal density in the hippocampal cornu ammonis (CA)–3 region of cysteamine hydrochloride-induced mouse model of GI disorder. Results obtained from the open field test (OFT), light and dark box test (LDBT), and elevated plus maze (EPM) test revealed that ranitidine treatment reduces anxiety-like behaviors in experimental animals. Nissl staining and immunohistochemical assessment of ionized calcium-binding adapter molecule (Iba)-1 positive microglia in cryosectioned brains indicated enhanced density of pyramidal neurons and reduced activation of microglia in the hippocampal CA–3 region of brains of ranitidine-treated experimental mice. Therefore, this study suggests that ranitidine mediates anxiolytic effects, which can be translated to establish a pharmacological regime to ameliorate anxiety-related symptoms in humans. |
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| id | doaj.art-9c68281562c44db98c97786a0b4814cd |
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| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T09:05:11Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-9c68281562c44db98c97786a0b4814cd2023-11-16T19:28:35ZengMDPI AGBrain Sciences2076-34252023-02-0113226610.3390/brainsci13020266Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal DisorderDivya Bharathi Selvaraj0Jemi Feiona Vergil Andrews1Muthuswamy Anusuyadevi2Mahesh Kandasamy3Laboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, IndiaLaboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, IndiaMolecular Neuro-Gerontology Laboratory, Department of Biochemistry, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, IndiaLaboratory of Stem Cells and Neuroregeneration, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620024, IndiaElevated levels of histamine cause over-secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. Ranitidine is an antihistamine drug widely used in the management of GI disorders, as it works by blocking the histamine−2 receptors in parietal cells, thereby reducing the production of HCl in the stomach. While some reports indicate the neuroprotective effects of ranitidine, its role against GI disorder-related anxiety remains unclear. Therefore, we investigated the effect of ranitidine against anxiety-related behaviors in association with changes in neuronal density in the hippocampal cornu ammonis (CA)–3 region of cysteamine hydrochloride-induced mouse model of GI disorder. Results obtained from the open field test (OFT), light and dark box test (LDBT), and elevated plus maze (EPM) test revealed that ranitidine treatment reduces anxiety-like behaviors in experimental animals. Nissl staining and immunohistochemical assessment of ionized calcium-binding adapter molecule (Iba)-1 positive microglia in cryosectioned brains indicated enhanced density of pyramidal neurons and reduced activation of microglia in the hippocampal CA–3 region of brains of ranitidine-treated experimental mice. Therefore, this study suggests that ranitidine mediates anxiolytic effects, which can be translated to establish a pharmacological regime to ameliorate anxiety-related symptoms in humans.https://www.mdpi.com/2076-3425/13/2/266anxietycysteamine HClhistamineranitidineelevated plus mazemicroglia |
| spellingShingle | Divya Bharathi Selvaraj Jemi Feiona Vergil Andrews Muthuswamy Anusuyadevi Mahesh Kandasamy Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder Brain Sciences anxiety cysteamine HCl histamine ranitidine elevated plus maze microglia |
| title | Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder |
| title_full | Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder |
| title_fullStr | Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder |
| title_full_unstemmed | Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder |
| title_short | Ranitidine Alleviates Anxiety-like Behaviors and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in the CA3 Region of the Hippocampus in a Cysteamine HCl-Induced Mouse Model of Gastrointestinal Disorder |
| title_sort | ranitidine alleviates anxiety like behaviors and improves the density of pyramidal neurons upon deactivation of microglia in the ca3 region of the hippocampus in a cysteamine hcl induced mouse model of gastrointestinal disorder |
| topic | anxiety cysteamine HCl histamine ranitidine elevated plus maze microglia |
| url | https://www.mdpi.com/2076-3425/13/2/266 |
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