Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knockout mice by reducing glutamate excitotoxicity

Shen, Yao; He, Ping; Fan, Yan ying; Zhang, Jian xiang; Yan, Hai Jing; Hu, Wei; Ohtsu, Hiroshi; Chen, Zhong

doi:10.1016/j.freeradbiomed.2009.12.021

Cited by 86 publications

(76 citation statements)

References 31 publications

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“…Both HDC-KO and WT mice had a pure C57BL/6 genetic background. To confirm the genotypes of the mice with respect to the HDC gene, tail biopsies were taken randomly from mice used in the experiment and analyzed by PCR, according to the procedure described in previous work [21,22] . The animals were housed individually in a temperature and humidity-controlled environment with ad libitum access to food and water.…”

Section: Animalsmentioning

confidence: 99%

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

et al. 2010

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Aim: Histamine plays an important role in morphine addiction and memory-dependent behavior. However, little is known about the effect of histamine on the impairment of memory after morphine withdrawal. This study was designed to investigate the effect of histamine on memory impairment induced by morphine withdrawal in histidine decarboxylase knockout (HDC-KO) and wild-type (WT) mice. Methods: WT and HDC-KO mice were given subcutaneous morphine or saline twice daily for 5 consecutive days. The mice received a cued or contextual fear conditioning session 7 days after the last injection. During subsequent days, mice received 4 cued or contextual extinction sessions (one session per day). Western blot was used to assess extracellular signal-regulated kinase (ERK) phosphorylation in the amygdala and hippocampus. Results: Morphine withdrawal did not affect the acquisition of cued or contextual fear responses. It impaired cued but not contextual fear extinction. The acquisition of cued and contextual fear responses was accelerated in HDC-KO mice. Histamine deficiency aggravated the impairment of cued fear extinction induced by morphine withdrawal, whereas histamine (icv, 5 µg/mouse) reversed this effect. Morphine withdrawal decreased ERK phosphorylation in the amygdala after cued fear extinction, especially in HDC-KO mice. Conclusion: These results suggest that morphine withdrawal specifically impairs cued fear extinction and histamine ameliorates this impairment. Its action might be mediated by the modulation of ERK phosphorylation in the amygdala. Histamine should be explored for possible roles in the prevention or treatment of morphine abuse and relapse.

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Section: Animalsmentioning

confidence: 99%

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

et al. 2010

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“…Moreover, we showed that carnosine suppresses the generation of mitochondrial reactive oxygen species to recover the expression of GLT-1 and then reduces the glutamate excitotoxicity; however, this effect is not through the carnosine-histamine pathway. 41 Modulation of GABA release may also be involved the protection by H3 antagonists. We found that clobenpropit reverses the neurotoxicity induced by NMDA in a concentration-dependent manner.…”

Section: ■ Possible Mechanisms By Which Histaminementioning

confidence: 99%

“…In a recent study, we found that carnosine significantly improves neurological function and decreases infarct size after permanent MCAO in both HDC knockout and the corresponding WT mice to the same extent, and this cannot be reversed by α-FMH. 41 It is suggested that the action of carnosine on permanent focal cerebral ischemia is not mediated by the carnosine-histidine-histamine pathway but by decreasing the glutamate levels and preserving the expression of GLT-1. But carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through the carnosine-histidinehistamine pathway and H1/H3 receptors.…”

Section: ■ Prospects For Histamine-related Agents In Cerebral Ischemiamentioning

confidence: 99%

Role of Histamine and Its Receptors in Cerebral Ischemia

Chen

2012

ACS Chem. Neurosci.

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Histamine is recognized as a neurotransmitter or neuromodulator in the brain, and it plays a major role in the pathogenic progression after cerebral ischemia. Extracellular histamine increases gradually after ischemia, and this may come from histaminergic neurons or mast cells. Histamine alleviates neuronal damage and infarct volume, and it promotes recovery of neurological function after ischemia; the H1, H2, and H3 receptors are all involved. Further studies suggest that histamine alleviates excitotoxicity, suppresses the release of glutamate and dopamine, and inhibits inflammation and glial scar formation. Histamine may also affect cerebral blood flow by targeting to vascular smooth muscle cells, and promote neurogenesis. Moreover, endogenous histamine is an essential mediator in the cerebral ischemic tolerance. Due to its multiple actions, affecting neurons, glia, vascular cells, and inflammatory cells, histamine is likely to be an important target in cerebral ischemia. But due to its low penetration of the blood-brain barrier and its wide actions in the periphery, histamine-related agents, like H3 antagonists and carnosine, show potential for cerebral ischemia therapy. However, important questions about the molecular aspects and pathophysiology of histamine and related agents in cerebral ischemia remain to be answered to form a solid scientific basis for therapeutic application.

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“…The anti-apoptotic effects of cAMP are seen in many types of neuronal systems, including cerebellar granule neurons [164][165][166][167][168][169], dopamine neurons [170], septal cholinergic neurons [171], and sympathetic and sensory neurons [172][173][174]. A clinical study on POAG patients treated with a food supplement containing forskolin and rutin (Kronek®) has shown an improvement of the electrophysiological activity of RGC as measured by PERG analysis [175,176].Carnosine is a di-peptide (alanine + histidine), found in large amounts in the eye lens, the brain (especially the primary olfactory ways) (5mM) and in voluntary muscles (20 mM) [177]. It has been shown to have neuroprotective effects on RGCs against glutamate and free radical toxicity [178,179], and also attenuate through similar mechanisms β-amyloid neurotoxicity [179].…”

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confidence: 99%

“…In the context of AD, carnosine has been suggested as a therapeutic agent, given its capability to act as a metal chelator, free radical scavenger as well as an inhibitor of Aβ toxicity [178]. In 2011 Corona et al investigated the potential beneficial effects of dietary carnosine supplementation (10 mM in drinking water) in 3xTg-AD mice [180], an AD animal model that develops an amyloid-and tau-dependent pathology, as well as AD-related cognitive deficits [171][172][173][174][175][176][177][178][179][180][181]. When Corona et al analyzed the effects of carnosine on this mouse model system, they found that carnosine was very effective in decreasing intraneuronal Aβ deposition in the hippocampus.…”

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confidence: 99%

Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

Pescosolido¹,

Pascarella²,

Buomprisco³

et al. 2014

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two distinct pathologies, despite similar pathophysiology and demographic distribution. Both diseases are neurodegenerative, chronic and progressive in nature, with irreversible neuronal cell loss. Furthermore, both POAG and AD disease primarily affect the elderly, with a strongly age-dependent incidence. The progressive debilitating course of both diseases has tremendous implications on an aging population [1]. For years Glaucoma has been associated with high IOP [2], although scientists had accepted this etiology with caution, since it was known that POAG could develop in subjects with normal or even low IOP. In fact, one out of three POAG patients has normotensive or low tension glaucoma [3]. This observation has led the scientific community to look for other possible causes of this slowly debilitating pathogenesis.The hallmark of neurodegenerative diseases is the death of specific neuron populations, and of those other neurons that are inter-connected and depend for their survival on the inputs from the main population (trans-synaptic degeneration). In Parkinson's disease accumulation of alfa-synuclein [4] causes the degeneration of dopaminergic neurons of the substantia nigra, in the midbrain, thus leading to the classic symptoms of Parkinson's such as tremor, akinesia, bradykinesia, and stiffness [5]. In AD there is a loss of neurons in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus [6]. Both amyloid plaques and neurofibrillary tangles are AbstractA third of people affected by primary open angle glaucoma (POAG) have normal or even low intraocular pressure (IOP), such as in the case of normotensive glaucoma and low pressure glaucoma. Therefore, high IOP, while remaining the most important risk factor for POAG development, is not the only one. POAG has been recognized to belong to the class of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's, and several recent studies have suggested possible links between Alzheimer's and glaucoma both from an epidemiological and a pathogenetic point of view. In fact, several pathogenetic factors are common between the two diseases: the diffuse axonal degeneration of ganglion cells, the presence of specific markers (such as amyloid-β) in the aqueous humor, the activation of caspases and the abnormal processing of amyloid precursor protein in retinal ganglion cells, the reduction of the intracranial pressure of the cerebrospinal fluid, the mutations of the gene that encodes for optineurine. Conflicting data have been reported concerning apolipoprotein E. Finally, numerous publications affirm the utility of molecules traditionally used in the treatment of neurodegenerative diseases (e.g. forskolin, L-carnosine, homotaurine, folic acid, acetylcholinesterase inhibitors, antioxidant vitamins, glatiramer acetate, etc.) also in the treatment of glaucoma.In the present research we ana...

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Carnosine protects against permanent cerebral ischemia in histidine decarboxylase knockout mice by reducing glutamate excitotoxicity

Cited by 86 publications

References 31 publications

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

Ameliorating effect of histamine on impairment of cued fear extinction induced by morphine withdrawal in histidine decarboxylase gene knockout mice

Role of Histamine and Its Receptors in Cerebral Ischemia

Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

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