Does endogenous zinc protoporphyrin modulate carbon monoxide formation from heme? Implications for long-term potentiation, memory, and cognitive function

1993 ◽  
Vol 71 (10-11) ◽  
pp. 753-754 ◽  
Author(s):  
Gerald S. Marks ◽  
Kanji Nakatsu ◽  
James F. Brien
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Cell Function ◽  
Physiological Role ◽  
Long Term Potentiation ◽  
Biological Properties ◽  
Zinc Protoporphyrin ◽  
Term Potentiation ◽  
Oxygenase Activity

Carbon monoxide, which is formed endogenously from heme catabolism catalyzed by heme oxygenase and shares some of the chemical and biological properties of nitric oxide, may play a similar role as a widespread signal transduction mechanism for the regulation of cell function and communication. Zinc protoporphyrin, an inhibitor of heme oxygenase, prevents induction of long-term potentiation. Zinc protoporphyrin is an endogenous substance and we suggest that it has a physiological role, by modulating heme oxygenase activity and, therefore, formation of carbon monoxide from heme. This in turn would modulate long-term potentiation, memory, and cognitive function.Key words: zinc protoporphyrin, carbon monoxide, heme oxygenase, long-term potentiation.

On the Respective Roles of Nitric Oxide and Carbon Monoxide in Long-Term Potentiation in the Hippocampus

1999 ◽  
Vol 6 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Min Zhuo ◽  
Jarmo T. Laitinen ◽  
Xiao-Ching Li ◽  
Robert D. Hawkins
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Guanylyl Cyclase ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
No Synthase ◽  
Term Potentiation ◽  
Stimulation Of

Perfusion of hippocampal slices with an inhibitor nitric oxide (NO) synthase blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

scholarly journals On the Respective Roles of Nitric Oxide and Carbon Monoxide in Long-Term Potentiation in the Hippocampus

1998 ◽  
Vol 5 (6) ◽  
pp. 467-480
Author(s):  
Min Zhuo ◽  
Jarmo T. Laitinen ◽  
Xiao-Ching Li ◽  
Robert D. Hawkins
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Guanylyl Cyclase ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
No Synthase ◽  
Term Potentiation ◽  
Stimulation Of

Perfusion of hippocampal slices with an inhibitor of nitric oxide (NO) synthase-blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

scholarly journals A physiological role for GABAA receptor desensitization – induction of long-term potentiation at inhibitory synapses

2020 ◽  
Author(s):  
Martin Field ◽  
Philip Thomas ◽  
Trevor G Smart
Keyword(s):  
Physiological Role ◽  
Long Term Potentiation ◽  
Inhibitory Synapses ◽  
Structural Basis ◽  
Inhibitory Neurotransmission ◽  
Term Potentiation ◽  
Physiological Relevance ◽  
Kinetic Effects ◽  
Physiological Impact

AbstractGABAA receptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.

Evidence for the Role of Endogenous Carbon Monoxide in Memory Processing

2007 ◽  
Vol 19 (4) ◽  
pp. 557-562 ◽  
Author(s):  
M. C. Cutajar ◽  
T. M. Edwards
Keyword(s):  
Carbon Monoxide ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Memory Research ◽  
Memory Processing ◽  
Important Target ◽  
Term Potentiation ◽  
Per Se

For a decade and a half, nitric oxide (NO) has been implicated in memory processing across a wide variety of tasks and species. Comparatively, endogenously produced carbon monoxide (CO) has lagged behind as a target for research into the pharmacological processes underlying memory formation. This is surprising given that CO is formed in memory-associated brain regions, is structurally similar to NO, and along with NO can activate guanylate cyclase, which is an enzyme well characterized in memory processing. Nevertheless, a limited number of electrophysiological investigations have concluded that endogenous CO is involved in long-term potentiation. Although not evidence for a role in memory per se, these studies did point to the possible importance of CO in memory processing. In addition, there is now evidence to suggest that endogenous CO is important in avoidance learning and possible for other tasks. This review therefore seeks to promote endogenous CO as a potentially important target for memory research.

scholarly journals Hippocampal long-term potentiation is normal in heme oxygenase-2 mutant mice

Neuron ◽  
1995 ◽  
Vol 15 (4) ◽  
pp. 867-873 ◽  
Author(s):  
Kenneth D. Poss ◽  
Mark J. Thomas ◽  
Alexander K. Ebralidze ◽  
Thomas J. O'Dell ◽  
Susumu Tonegawa
Keyword(s):  
Heme Oxygenase ◽  
Long Term Potentiation ◽  
Mutant Mice ◽  
Term Potentiation

scholarly journals The Ras-like GTPase Rem2 is a potent endogenous inhibitor of calcium/calmodulin-dependent kinase II activity

2017 ◽  
Author(s):  
Leandro Royer ◽  
Josiah J. Herzog ◽  
Katelyn Kenny ◽  
Boriana Tzvetkova ◽  
Jesse C. Cochrane ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Catalytic Domain ◽  
Physiological Role ◽  
Long Term Potentiation ◽  
Endogenous Inhibitor ◽  
Calcium Calmodulin Dependent ◽  
Term Potentiation ◽  
Cellular Context ◽  
Activity Dependent

AbstractCaMKII is a well-characterized, abundant protein kinase that regulates a diverse set of functions in a tissue specific manner. For example, in heart muscle, CaMKII regulates Ca2+ homeostasis while in neurons CaMKII regulates activity-dependent dendritic remodeling and Long Term Potentiation (LTP), a biological correlate of learning and memory. Previously, we identified the noncanonical GTPase Rem2 as a critical regulator of dendrite branching and synapse formation in the vertebrate nervous system. Here, we report that Rem2 directly interacts with CaMKII and potently inhibits the activity of the intact holoenzyme, a previously undescribed function for the Rem2 protein. To date, only one other endogenous inhibitor of CaMKII has been described: CaMKIIN, which blocks CaMKII activity through binding to the catalytic domain. Our data suggest that Rem2 inhibits CaMKII through a novel mechanism, as inhibition requires the presence of the association domain of CaMKII. Our biochemical finding that Rem2 is a direct, endogenous inhibitor of CaMKII activity, coupled with known functions of Rem2 in neurons, provides a framework which will enable future experiments probing the physiological role of CaMKII inhibition in a cellular context.

scholarly journals Oat Extract Avenanthramide-C Reverses Hippocampal Long-Term Potentiation Decline in Tg2576 Mice

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6105
Author(s):  
Yu-Young Lee ◽  
Ming Wang ◽  
Yurim Son ◽  
Eun-Ju Yang ◽  
Moon-Seok Kang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Mouse Model ◽  
Glycogen Synthase ◽  
Hippocampal Slices ◽  
Amyloid Β ◽  
Long Term Potentiation ◽  
Biological Properties ◽  
Tg2576 Mouse ◽  
Term Potentiation

Memory deterioration in Alzheimer’s disease (AD) is thought to be underpinned by aberrant amyloid β (Aβ) accumulation, which contributes to synaptic plasticity impairment. Avenanthramide-C (Avn-C), a polyphenol compound found predominantly in oats, has a range of biological properties. Herein, we performed methanolic extraction of the Avns-rich fraction (Fr. 2) from germinated oats using column chromatography, and examined the effects of Avn-C on synaptic correlates of memory in a mouse model of AD. Avn-C was identified in Fr. 2 based on 1H-NMR analysis. Electrophysiological recordings were performed to examine the effects of Avn-C on the hippocampal long-term potentiation (LTP) in a Tg2576 mouse model of AD. Avn-C from germinated oats restored impaired LTP in Tg2576 mouse hippocampal slices. Furthermore, Avn-C-facilitated LTP was associated with changes in the protein levels of phospho-glycogen synthase kinase-3β (p-GSK3β-S9) and cleaved caspase 3, which are involved in Aβ-induced synaptic impairment. Our findings suggest that the Avn-C extract from germinated oats may be beneficial for AD-related synaptic plasticity impairment and memory decline.

Inhibition of hippocampal heme oxygenase, nitric oxide synthase, and long-term potentiation by metalloporphyrins

Neuron ◽  
1994 ◽  
Vol 13 (5) ◽  
pp. 1225-1233 ◽  
Author(s):  
Mollie K. Meffert ◽  
Jane E. Haley ◽  
Erin M. Schuman ◽  
Howard Schulman ◽  
Daniel V. Madison
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Oxide Synthase
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