Omeprazole treatment manifests anxiolytic effects in a cysteamine hydrochloride induced mouse model of gastrointestinal disorder

Rethinavel, Harini Sri; Selvaraj, Divya Bharathi; Balakrishnan, Sathya Jeevitha; Andrews, Jemi Feiona Vergil; Joseph, Jerly Helan Mary; Kandasamy, Mahesh

doi:10.1016/j.heliyon.2022.e09787

Cited by 5 publications

(8 citation statements)

References 39 publications

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“…Results revealed that cysteamine HCl-treated animal exhibit enhanced anxiety-related behavior. This data validates our previous findings that cysteamine HCl treatment can mediate ulcerative problems in the GI tract and induce oxidative stress and neuroinflammation in the brain [5]. While the neuroinflammation seen in various GI disorders has been known to induce pathogenic alteration in the hippocampus affecting the morphological features and neuroplasticity of the pyramidal neurons predominately in the CA3 region, subjects with gastric and duodenal ulcers have been shown to exhibit an increased level of histamine [43,44].…”

Section: Discussionsupporting

confidence: 90%

“…After OFT, the animal was placed in its home cage. At the end of each trial, the open field arena was cleaned with 70% ethanol [5,19,20].…”

Section: Open Field Testmentioning

confidence: 99%

“…The entire LTB was wiped with 70% ethanol and dried. The total time spent in the light, and dark zone, by experimental animals were estimated from trajectories recorded using SMART 3.0 software [5,20].…”

Section: Light and Dark Box Testmentioning

confidence: 99%

“…After the completion of each trial, the animal was placed back into the home cage. The arms and central area of EPM were cleaned with 70% ethanol [5,20].…”

Section: Elevated Plus Mazementioning

confidence: 99%

“…Gastrointestinal (GI) disorders and anxiety are widespread and growing clinical concerns worldwide [1,2]. The clinical characteristics of GI disorders are complex that often known to be associated with anxiety-related symptoms [3][4][5]. The etiology and overlapping pathomechanisms responsible for GI disorders and anxiety remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

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Ranitidine Alleviates Anxiety-Like Behaviour and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in CA3 Region of the Hippocampus in A Cysteamine Hcl-Induced Mouse Model of Gastrointestinal Disorder

Selvaraj¹,

Andrews²,

Anusuyadevi³

et al. 2023

Preprint

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Elevated levels of histamine cause the secretion of gastric hydrochloric acid (HCl), leading to gastrointestinal (GI) disorders and anxiety. While aberrant levels of histamine mediate neuroinflammation, pathogenic alterations in the hippocampus of the brain have been linked to anxiety. Eventually, antihistamine drugs that are used against GI disorders appear to be anxiolytic agents. Ranitidine is a widely used antihistamine drug to manage GI disorders as it works by blocking the histamine (H)-2 receptors in oxyntic cells thereby, reducing the HCl production in the stomach. Though some reports indicate the neuroprotective effects of ranitidine, its role against GI disorders related to anxiety remains unclear. Therefore, we investigated the effect of ranitidine against anxiety-related behaviors, neuronal density, and signs of microglia activation in the hippocampal CA3 region of cysteamine HCl-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) revealed that ranitidine treatment reduces anxiety-like behaviors in experimental animals. Nissl staining and immunohistochemical assessment of Iba-1 positive microglia in the cryosectioned brains revealed that the ranitidine treatment enhances the density of pyramidal neurons in association with reduced activation of microglia in the CA3 region of the hippocampus of experimental mice.

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Section: Discussionsupporting

confidence: 90%

“…After OFT, the animal was placed in its home cage. At the end of each trial, the open field arena was cleaned with 70% ethanol [5,19,20].…”

Section: Open Field Testmentioning

confidence: 99%

Section: Light and Dark Box Testmentioning

confidence: 99%

“…After the completion of each trial, the animal was placed back into the home cage. The arms and central area of EPM were cleaned with 70% ethanol [5,20].…”

Section: Elevated Plus Mazementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ranitidine Alleviates Anxiety-Like Behaviour and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in CA3 Region of the Hippocampus in A Cysteamine Hcl-Induced Mouse Model of Gastrointestinal Disorder

Selvaraj¹,

Andrews²,

Anusuyadevi³

et al. 2023

Preprint

View full text Add to dashboard Cite

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Long-term administration of omeprazole in mice: a study of behavior, inflammatory, and oxidative stress alterations with focus on central nervous system

Coelho,

Costa Júnior,

da Silva

et al. 2024

Naunyn-Schmiedeberg's Arch Pharmacol

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Cysteamine HCl Administration Impedes Motor and Olfactory Functions Accompanied by Reduced Dopaminergic Neurons in Experimental Mice: A Preclinical Mimetics Relevance to Parkinson’s Disease

Selvaraj,

Panneerselvam,

Vergil Andrews

et al. 2024

Preprint

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Cysteamine HCl has been established as a potent ulcerogenic agent of the gastrointestinal (GI) system. GI dysfunction and olfactory deficits are the most common clinical symptoms of many movement disorders including Parkinson's disease (PD). Cysteamine HCl has been shown to interfere with dopamine, a neurotransmitter crucial for motor, olfactory, and cognitive functions. However, the reports on the effect of cysteamine HCl treatment on the behavior and dopamine system appear to be inconsistent. Therefore, we revisited the impact of cysteamine HCl on motor function in experimental mice using a battery of behavioral tests such as pole test (PT), beam walking test (BWT), and rotarod test (RDT), while the olfactory ability and cognitive functions were examined through food buried test (FBT) and Y maze. Furthermore, we investigated the effect of cysteamine HCl on the density of dopaminergic tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) and olfactory bulb (OB) of experimental mice using immunohistochemistry. Results revealed that cysteamine HCl administration in mice induced significant impairments in motor balance and coordination, as their movement-related performance was markedly reduced in behavioral tasks. Mice exposed to cysteamine HCl showed a pronounced reduction in odor discrimination ability and cognitive impairments. Strikingly, the number of TH-positive neurons was found to be reduced in the SN and OB of the cysteamine HCl-treated group which is a bonafide neuropathogenic hallmark of PD. This study highlights the potential neurotoxic effects of cysteamine HCl in experimental brains and suggests further investigation into its role in pathogenesis of Parkinsonism.

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Omeprazole treatment manifests anxiolytic effects in a cysteamine hydrochloride induced mouse model of gastrointestinal disorder

Cited by 5 publications

References 39 publications

Ranitidine Alleviates Anxiety-Like Behaviour and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in CA3 Region of the Hippocampus in A Cysteamine Hcl-Induced Mouse Model of Gastrointestinal Disorder

Ranitidine Alleviates Anxiety-Like Behaviour and Improves the Density of Pyramidal Neurons upon Deactivation of Microglia in CA3 Region of the Hippocampus in A Cysteamine Hcl-Induced Mouse Model of Gastrointestinal Disorder

Long-term administration of omeprazole in mice: a study of behavior, inflammatory, and oxidative stress alterations with focus on central nervous system

Cysteamine HCl Administration Impedes Motor and Olfactory Functions Accompanied by Reduced Dopaminergic Neurons in Experimental Mice: A Preclinical Mimetics Relevance to Parkinson’s Disease

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