Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5‐HT turnover in histidine decarboxylase‐KO mice

Dere, Ekrem; Souza-Silva, M. A. De; Spieler, Richard E.; Lin, Jian‐Sheng; Ohtsu, Hiroshi; Haas, Helmut L.; Huston, Joseph P.

doi:10.1111/j.1460-9568.2004.03546.x

Cited by 83 publications

(75 citation statements)

References 45 publications

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“…These mice have been used to clarify the role of histamine in anaphylactic responses and allergic inflammation (53)(54)(55), as well as in several neurophysiological functions (33,56). Because it is difficult to achieve complete and long-lasting elimination of the effects of histamine in vivo using pharmacological approaches (32), HDC Ϫ/Ϫ mice provide a good model in which to study autoimmune responses against CNS myelin in the virtual absence of any kind of regulation mediated by histamine.…”

Section: Discussionmentioning

confidence: 99%

A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice

Musio¹,

Gallo²,

Scabeni³

et al. 2006

The Journal of Immunology

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Histamine can modulate the cytokine network and influence Th1 and Th2 balance and Ab-isotype switching. Thus, pharmacological blockade or genetic deletion of specific histamine receptors has been shown to reduce the severity of experimental autoimmune encephalomyelitis (EAE), a prototypic Th1-mediated disease with similarities to human multiple sclerosis. To study the comprehensive contribution of endogenous histamine to the expression of EAE, we attempted to induce EAE in histidine decarboxylase-deficient mice, which are genetically unable to make histamine. In this study, we show that EAE is significantly more severe in HDC−/−, histamine-deficient mice, with diffuse inflammatory infiltrates, including a prevalent granulocytic component, in the brain and cerebellum. Unlike splenocytes from wild-type mice, splenocytes from HDC−/− mice do not produce histamine in response to the myelin Ag, whereas production of IFN-γ, TNF, and leptin are increased in HDC−/− splenocytes in comparison to those from wild-type mice. Endogenous histamine thus appears to regulate importantly the autoimmune response against myelin and the expression of EAE, in this model, and to limit immune damage to the CNS. Understanding which receptor(s) for histamine is/are involved in regulating autoimmunity against the CNS might help in the development of new strategies of treatment for EAE and multiple sclerosis.

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Section: Discussionmentioning

confidence: 99%

A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice

Musio¹,

Gallo²,

Scabeni³

et al. 2006

The Journal of Immunology

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“…Recently, a few cases of improved rotarod performance after gene inactivation in mice have been described. Mice deficient for the histidine decarboxylase gene have histamine deficiency and show improved rotarod performance (14). These mice have altered acetylcholine concentrations in the frontal cortex and the neostriatum, which may be related to the observed behavioral changes.…”

Section: Vol 25 2005mentioning

confidence: 99%

Generation and Characterization of Rac3 Knockout Mice

Corbetta¹,

Gualdoni²,

Albertinazzi³

et al. 2005

Molecular and Cellular Biology

112

128

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Rac proteins are members of the Rho family of GTPases involved in the regulation of actin dynamics. The three highly homologous Rac proteins in mammals are the ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized Rac3. We show here that Rac3 mRNA is widely and specifically expressed in the developing nervous system, with highest concentration at embryonic day 13 in the dorsal root ganglia and ventral spinal cord. At postnatal day 7 Rac3 appears particularly abundant in populations of projection neurons in several regions of the brain, including the fifth layer of the cortex and the CA1-CA3 region of the hippocampus. We generated mice deleted for the Rac3 gene with the aim of analyzing the function of this GTPase in vivo. Rac3 knockout animals survive embryogenesis and show no obvious developmental defects. Interestingly, specific behavioral differences were detected in the Rac3-deficient animals, since motor coordination and motor learning on the rotarod was superior to that of their wild-type littermates. No obvious histological or immunohistological differences were observed at major sites of Rac3 expression. Our results indicate that, in vivo, Rac3 activity is not strictly required for normal development in utero but may be relevant to later events in the development of a functional nervous system.

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“…32) In addition, HDC knockout mice also showed reduced exploratory behavior in the open-field, reduced locomotor activity in the home cage in the dark, increased measures of anxiety on the elevated plus-maze, impairments in long-term object recognition memory, and enhanced motor coordination on the rotorod. [32][33][34][35][36] In the present study, the increase in expression levels of HDC mRNA in the amygdala region after EMA administration suggests that the anxiolytic-like activity are dependent on HDC expression in the amygdala.…”

Section: Discussionmentioning

confidence: 68%

Involvement of Histaminergic System in the Anxiolytic-Like Activities of <i>Morus alba</i> Leaves in Mice

Lee

Kim

Lee

et al. 2013

Biological & Pharmaceutical Bulletin

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The aim of this study was to identify the effects of 85% methanolic extract of Morus alba leaves (EMA), which is a traditional herb, in mice. The effects of EMA on the anxiolytic-like behaviour were studied using the elevated plus maze (EPM) and hole-board test. To elucidate the mode of action of the anxiolytic-like effects of EMA, the mice were subjected to the co-administration of EMA (200 mg/kg, per os (p.o.)) and either antagonist. EMA (at 200 or 400 mg/kg) significantly increased the percentages of time-spent in the open arms and entries into the open arms of the EPM versus vehicle-treated control group (p<0.05). Moreover, in the hole-board test, EMA (200 and 400 mg/kg) significantly increased the number of head-dips versus vehicle-treated control group (p<0.05). However, there were no changes in the locomotor activity and myorelaxant effects in any group compared with the vehicle-treated control group. In addition, the anxiolytic-like effects of EMA were abolished by thioperamide (10 mg/kg, intraperitoneally (i.p.)), which is a histamine H 3 receptor antagonist. Moreover, results from reverse transcription polymerase chain reaction (RT-PCR) also revealed that the amygdalal histidine decarboxylase mRNA expression levels in EMA (200 mg/kg)-treated group were significantly higher than those in the vehicle-treated controls (p<0.05). These results suggest that EMA might prove to be an effective anxiolytic agent and that EMA acts via the histaminergic system in central nerve system. Key words anxiety; Morus alba; elevated plus-maze; histamine; thioperamide Mulberry tree (Morus alba L., Moraceae) is cultivated in China, Japan and Korea and is an important herbal material in traditional Chinese medicine. For example, the root bark of mulberry trees has long been used for anti-inflammatory, diuretic, antitussive, and antipyretic purposes in Oriental medicine.1) Moreover, fruit extract of M. alba was reported to modulate the monoamine oxidase activity during exercise and to promote the capability of physical activities.2) In addition to those herbal materials from M. alba, the leaves of this plant are one of the well-known traditional Chinese medicinal herbs and have been traditionally used to cure or prevent diabetic hyperglycemia.3,4) Based on those traditional usages, researchers reported that nitric oxide synthase positive neurons were decreased by the treatment with M. alba extracts in the various hypothalamic areas in the streptozotocin-induced diabetic rat brain. 4) Interestingly, those hypothalamic areas, including the paraventricular nucleus and ventromedial hypothalamic nucleus are rich in histaminergic neurons originating from the tuberomammillary body.5) These findings suggest a possibility that the leaves of M. alba may affect the activity of the histaminergic nervous system. Moreover, several clinically useful anxiolytics have been found to affect the turnover rate of brain histamine in the rat brain. For example, diazepam inhibits histamine turnover by acting on γ-aminobutyric acid (GABA) A receptors ...

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Changes in motoric, exploratory and emotional behaviours and neuronal acetylcholine content and 5‐HT turnover in histidine decarboxylase‐KO mice

Cited by 83 publications

References 45 publications

A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice

A Key Regulatory Role for Histamine in Experimental Autoimmune Encephalomyelitis: Disease Exacerbation in Histidine Decarboxylase-Deficient Mice

Generation and Characterization of Rac3 Knockout Mice

Involvement of Histaminergic System in the Anxiolytic-Like Activities of <i>Morus alba</i> Leaves in Mice

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