Dexmedetomidine Reduces Long-term Potentiation in Mouse Hippocampus

Takamatsu, Isao; Iwase, Ayano; Ozaki, Makoto; Kazama, Tomiei; Wada, Keiji; Sekiguchi, Masayuki

doi:10.1097/01.anes.0000296076.04510.e1

Cited by 32 publications

(17 citation statements)

References 46 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding is consistent with the report by Takamatsu et al [8], which showed that DEX impairs LTP induction in mouse hippocampal slices. In contrast, another in vitro report found that the same condition did not reduce the induction and maintenance of LTP in the CA1 area of the rat hippocampus [13].…”

Section: Discussionsupporting

confidence: 94%

“…Several studies have investigated the influence of DEX on hippocampal long-term potentiation (LTP), a mechanism involved in information storage during learning and memory [7]. For instance, Takamatsu et al [8] showed that DEX impairs LTP induction in area CA1 of mouse hippocampal slices. However, no report has extrapolated the DEX-induced LTP suppression observed in animal studies to clinical situations.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats

et al. 2014

View full text Add to dashboard Cite

Purpose: The purpose of the present study was to evaluate the effect of dexmedetomidine (DEX) on hippocampal synaptic activity in vivo. Methods:The adult rats used for this study received a bolus intraperitoneal injection of 3, 10, 30, or 100 μg/kg of DEX or an equivalent volume of saline. Electrophysiological Results: Intraperitoneal administration of DEX at doses of 30 and 100 μg/kg induced a range of sedative effects. AUC measurements were significantly lower in the 30 and 100 μg/kg groups when compared to the vehicle rats (vehicle: 8.81 ± 0.49, n = 7; DEX 30 µg/kg: 6.02 ± 0.99, n = 6; DEX 100 µg/kg: 5.10 ± 0.43, n = 5; P < 0.05). Conclusion:Our in vivo study revealed that sedative doses of DEX impair the induction of hippocampal long-term potentiation (LTP). These findings may signify a causal link between DEX-induced sedative action and hippocampal LTP suppression, providing a better understanding of the mechanisms underlying the DEX-induced sedative and/or amnestic effect.

show abstract

Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…38,39 Field excitatory postsynaptic potentials (fEPSPs) are the sum of individual signals from many cells, including inhibitory GABArgic interneurons that have extensive arbors that innervate pyramidal cells. Individual GABArgic interneurons can powerfully inhibit thousands of excitatory pyramidal neurons.…”

Section: Discussionmentioning

confidence: 99%

α2-Adrenergic Receptor and Isoflurane Modulation of Presynaptic Ca2+ Influx and Exocytosis in Hippocampal Neurons

2016

View full text Add to dashboard Cite

Background Evidence indicates that the anesthetic-sparing effects of α2-adrenergic receptor (AR) agonists involve α2A-AR heteroreceptors on nonadrenergic neurons. Since volatile anesthetics inhibit neurotransmitter release by reducing synaptic vesicle (SV) exocytosis, the authors hypothesized that α2-AR agonists inhibit nonadrenergic SV exocytosis and thereby potentiate presynaptic inhibition of exocytosis by isoflurane. Methods Quantitative imaging of fluorescent biosensors of action potential–evoked SV exocytosis (synaptophysin-pHluorin) and Ca2+ influx (GCaMP6) were used to characterize presynaptic actions of the clinically used α2-AR agonists dexmedetomidine and clonidine, and their interaction with isoflurane, in cultured rat hippocampal neurons. Results Dexmedetomidine (0.1 μM, n = 10) or clonidine (0.5 μM, n = 8) inhibited action potential–evoked exocytosis (54 ± 5% and 59 ± 8% of control, respectively; P < 0.001). Effects on exocytosis were blocked by the subtype-nonselective α2-AR antagonist atipamezole or the α2A-AR–selective antagonist BRL 44408 but not by the α2C-AR–selective antagonist JP 1302. Dexmedetomidine inhibited exocytosis and presynaptic Ca2+ influx without affecting Ca2+ coupling to exocytosis, consistent with an effect upstream of Ca2+–exocytosis coupling. Exocytosis coupled to both N-type and P/Q-type Ca2+ channels was inhibited by dexmedetomidine or clonidine. Dexmedetomidine potentiated inhibition of exocytosis by 0.7 mM isoflurane (to 42 ± 5%, compared to 63 ± 8% for isoflurane alone; P < 0.05). Conclusions Hippocampal SV exocytosis is inhibited by α2A-AR activation in proportion to reduced Ca2+ entry. These effects are additive with those of isoflurane, consistent with a role for α2A-AR presynaptic heteroreceptor inhibition of nonadrenergic synaptic transmission in the anesthetic-sparing effects of α2A-AR agonists.

show abstract

“…α 2 -ARs and imidazoline I 2 receptors are affected by DEX. The observation that imidazoline I 2 receptors are involved in the DEX-mediated long-term potentiation reduction provides novel information on the basic actions of DEX in the CNS (28). Epidermal growth factor receptor transactivation in astrocytes in the mature brain in vivo represents an important process in response to α 2 -AR stimulation, and it may lead to ERK1/2 phosphorylation in astrocytes and adjacent neurons (29).…”

Section: Signaling Pathwaysmentioning

confidence: 99%

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

Cai

Jia

et al. 2014

Molecular Medicine Reports

113

View full text Add to dashboard Cite

Abstract. Dexmedetomidine (DEX), a highly specific α 2 -adrenergic agonist, which exhibits anaesthetic-sparing, analgesia and sympatholytic properties. DEX modulates gene expression, channel activation, transmitter release, inflammatory processes and apoptotic and necrotic cell death. It has also been demonstrated to have protective effects in a variety of animal models of ischemia/reperfusion (I/R) injury, including the intestine, myocardial, renal, lung, cerebral and liver. The broad spectrum of biological activities associated with DEX continues to expand, and its diverse effects suggest that it may offer a novel therapeutic approach for the treatment of human diseases with I/R involvement.

show abstract

Dexmedetomidine Reduces Long-term Potentiation in Mouse Hippocampus

Abstract: Dexmedetomidine impairs LTP in area CA1 of the mouse hippocampus via imidazoline type 2 receptors and alpha2-adrenoceptors.

Cited by 32 publications

References 46 publications

Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats

Dexmedetomidine suppresses long-term potentiation in the hippocampal CA1 field of anesthetized rats

α2-Adrenergic Receptor and Isoflurane Modulation of Presynaptic Ca2+ Influx and Exocytosis in Hippocampal Neurons

Molecular targets and mechanism of action of dexmedetomidine in treatment of ischemia/reperfusion injury (Review)

Contact Info

Product

Resources

About