Evidence for the involvement of hippocampal CO production in the acquisition and consolidation of inhibitory avoidance learning

Bernabeu, Ramón; Princ, F; Ml, de Stein; C, Fin; Aa, Juknat; Batile, A; Izquierdo, Iván; Jh, Medina

doi:10.1097/00001756-199502000-00027

Cited by 23 publications

(9 citation statements)

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“…Although we could not exclude the possibility that heme oxygenase-t mRNA was induced by NO donors as a defense mechanism to the oxidative stress, it is tempting to speculate on the possibility of an interaction between the CO/heme oxygenase system and the NO/NOS system in the human brain under some pathophysiological conditions. Indeed, in the CNS, CO and NO have been shown to be involved in long-term potentiation (Stevens and Wang, 1993;Zhuo et al, 1993;Fin et al, 1994;Bernabeu et al, 1995), which is, however, still controversial (Meffert et al, 1994;Bing et al, 1995;Poss et al, 1995). CO was shown to increase the basal secretion of CRH from rat hypothalamic cell cultures, and a heme oxygenase inhibitor, zinc protoporphyrin IX, decreased CRH secretion (Parkes et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Expression of Heme Oxygenase Isozyme mRNAs in the Human Brain and Induction of Heme Oxygenase‐1 by Nitric Oxide Donors

Takahashi¹,

Hara²,

Suzuki³

et al. 1996

Journal of Neurochemistry

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Heme oxygenase is an essential enzyme in the heme catabolism that produces carbon monoxide (CO). This study was designed to examine the expression of two heme oxygenase isozyme mRNAs in the human brain and to explore the involvement of nitric oxide (NO) and various neuropeptides in the regulation of their expression. Northern blot analysis showed the expression of heme oxygenase‐1 and heme oxygenase‐2 mRNAs in every region of the brain examined, with the highest levels found in the frontal cortex, temporal cortex, occipital cortex, and hypothalamus. In a human glioblastoma cell line, T98G, treatment with any of three types of NO donors—sodium nitroprusside, 3‐morpholinosydnonimine, and S‐nitroso‐l‐glutathione—caused a significant increase in the levels of heme oxygenase‐1 mRNA but not in the levels of heme oxygenase‐2 and heat‐shock protein 70 mRNAs. Sodium nitroprusside increased the levels of heme oxygenase‐1 protein but not the levels of heat‐shock protein 70 in T98G cells. The increase in content of heme oxygenase‐1 mRNA caused by sodium nitroprusside was completely abolished by the treatment with actinomycin D. On the other hand, the levels of heme oxygenase isozyme mRNAs were not noticeably changed in T98G cells following the treatment with 8‐bromo cyclic GMP, sodium nitrite, or various neuropeptides, such as calcitonin gene‐related peptide, endothelin‐1, and corticotropin‐releasing hormone. The present study has shown the expression profiles of heme oxygenase‐1 and ‐2 mRNAs in the human brain and the induction of heme oxygenase‐1 mRNA caused by NO donors in T98G cells. These findings raise a possibility that the CO/heme oxygenase system may function in concert with the NO/NO synthase system in the brain.

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Section: Discussionmentioning

confidence: 99%

Expression of Heme Oxygenase Isozyme mRNAs in the Human Brain and Induction of Heme Oxygenase‐1 by Nitric Oxide Donors

Takahashi¹,

Hara²,

Suzuki³

et al. 1996

Journal of Neurochemistry

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“…BVR converts BV to the stable product bilirubin (BR). Activities of HO and BVR are high in nervous tissues, and heme degradation products have been shown to play important roles in neuronal function [15][16][17][18] and neuroprotection [19][20][21][22]. Oxidative and inflammatory challenges upregulate the inducible form of heme oxygenase (HO-1), also known as heat shock protein 32 (HSP32), and BVR [23,24].…”

Section: Role Of Ho and The Biliverdin Reductase (Bvr) System In Neurmentioning

confidence: 99%

Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin

et al. 2020

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Phytocannabinoids protect neurons against stressful conditions, possibly via the heme oxygenase (HO) system. In cultures of primary mesencephalic neurons and neuroblastoma cells, we determined the capability of cannabidiol (CBD) and tetrahydrocannabinol (THC) to counteract effects elicited by complex I-inhibitor rotenone by analyzing neuron viability, morphology, gene expression of IL6, CHOP, XBP1, HO-1 (stress response), and HO-2, and in vitro HO activity. Incubation with rotenone led to a moderate stress response but massive degeneration of dopaminergic neurons (DN) in primary mesencephalic cultures. Both phytocannabinoids inhibited in-vitro HO activity, with CBD being more potent. Inhibition of the enzyme reaction was not restricted to neuronal cells and occurred in a non-competitive manner. Although CBD itself decreased viability of the DNs (from 100 to 78%), in combination with rotenone, it moderately increased survival from 28.6 to 42.4%. When the heme degradation product bilirubin (BR) was added together with CBD, rotenone-mediated degeneration of DN was completely abolished, resulting in approximately the number of DN determined with CBD alone (77.5%). Using N18TG2 neuroblastoma cells, we explored the neuroprotective mechanism underlying the combined action of CBD and BR. CBD triggered the expression of HO-1 and other cell stress markers. Co-treatment with rotenone resulted in the super-induction of HO-1 and an increased in-vitro HO-activity. Co-application of BR completely mitigated the rotenone-induced stress response. Our findings indicate that CBD induces HO-1 and increases the cellular capacity to convert heme when stressful conditions are met. Our data further suggest that CBD via HO may confer full protection against (oxidative) stress when endogenous levels of BR are sufficiently high.

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“…Knockout of the gene encoding heme oxygenase‐2 in mice produced no apparent abnormality in hippocampal LTP (Poss et al ., 1995). Although endogenous CO may have a facilitatory role in learning (Fin et al ., 1994; Bernabeu et al ., 1995), some studies have suggested that CO has suppressive effects on learning (Bing et al ., 1995; Morgan et al ., 1998). CO suppresses the induction of LTP in layer V of the auditory cortex (Wakatsuki et al ., 1998b).…”

Section: Introductionmentioning

confidence: 99%

Suppression of the induction of long‐term depression by carbon monoxide in rat cerebellar slices

Shibuki

Kimura

Wakatsuki³

2001

Eur J of Neuroscience

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Carbon monoxide (CO) suppresses brain functions at doses lower than that suppressing oxygen (O(2)) supply to the brain, and the cerebellum is one of the sites most susceptible to the neurotoxic effects of CO. We investigated the effects of CO on the induction of cerebellar long-term depression (LTD) in the synapses between parallel fibres (PFs) and Purkinje cells. CO, at concentrations between 8 nM and 5 microM, exhibited almost no effect on synaptic responses in Purkinje cells, O(2) consumption and NO release from PFs in rat cerebellar slices. However, the induction of LTD was significantly suppressed by CO at concentrations between 40 and 200 nM. The suppressive effect of 40 nM CO was antagonized by 10 microM NOR3, an NO donor. In contrast, CO exhibited no clear effect on the induction of LTD at concentrations between 1 and 5 microM. The induction of LTD, suppressed by 10 microM N(G)-nitro-L-arginine, an inhibitor of NO synthase, was not restored by 5 microM CO. CO is not only a neurotoxic substance but also a candidate for an intercellular messenger. delta-Aminolevulinate (30 microM), a substance facilitating endogenous CO production, suppressed the induction of LTD, and the effect of delta-aminolevulinate was antagonized by 10 microM NOR3. These findings suggest that CO may have a suppressive effect on the induction of cerebellar LTD at nanomolar concentrations, probably via its effects on NO/cGMP signalling.

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Evidence for the involvement of hippocampal CO production in the acquisition and consolidation of inhibitory avoidance learning

Cited by 23 publications

References 0 publications

Expression of Heme Oxygenase Isozyme mRNAs in the Human Brain and Induction of Heme Oxygenase‐1 by Nitric Oxide Donors

Expression of Heme Oxygenase Isozyme mRNAs in the Human Brain and Induction of Heme Oxygenase‐1 by Nitric Oxide Donors

Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin

Suppression of the induction of long‐term depression by carbon monoxide in rat cerebellar slices

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