A critical role for the glial‐derived neuromodulator <scp>d</scp>‐serine in the age‐related deficits of cellular mechanisms of learning and memory

Mothet, Jean-Pierre; Rouaud, Emilie; Sinet, Pierre-Marie; Potier, Brigitte; Jouvenceau, Anne; Dutar, P.; Videau, Catherine; Epelbaum, Jacques; Billard, J.M.

doi:10.1111/j.1474-9726.2006.00216.x

Cited by 146 publications

(151 citation statements)

References 36 publications

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“…It is well documented that NMDAR activation plays an essential role in the induction of LTP, and NMDAR hypofunction is observed in aged animals or patients with age-related neurodegenerative diseases (Barnes et al, 1997;Shankar et al, 1998;Clayton et al, 2002;Mothet et al, 2006;Battaglia et al, 2007;Turpin et al, 2009). More evidence indicates that the alterations in NMDAR functional properties are primarily responsible for aging-associated deficits of synaptic plasticity (Potier et al, 2000;Clayton et al, 2002;Boric et al, 2008;Turpin et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…To investigate whether the function of NMDAR was modulated by thiol agents, the NMDAR-mediated fEPSPs were isolated by pharmacologic manipulation. Similar to those in previous reports with some improvement (Kamsler & Segal, 2003;Mothet et al, 2006), the perfusion medium was changed into magnesium-free artificial cerebrospinal fluid (ACSF) containing 10 lM glycine and 10 lM CNQX, an AMPA receptor antagonist, to isolate NMDAR-mediated fEPSPs. It was found that in the hippocampal CA1 area of adult rats, bath application of 50 lM DTT induced an increase in the magnitude of isolated NMDAR-mediated synaptic potentials, while 100 lM DTNB decreased the magnitude of isolated NMDAR-mediated fEPSPs significantly ( Fig.…”

Section: Modulation Of Thiol Redox Status With Reductants Directly Rementioning

confidence: 99%

“…Moreover, recent studies demonstrate that the alteration in NMDAR functional properties, rather than in their expression or density, is the mechanism of age-related deficits in NMDAR (Potier et al, 2000;Clayton et al, 2002;Boric et al, 2008;Turpin et al, 2009). Interestingly, D-serine, an amino acid that serves as an endogenous ligand for the strychnine-insensitive glycine-binding site of NMDAR, rescues the impaired NMDARdependent synaptic plasticity in aged animals (Mothet et al, 2006), suggesting that the upregulation of NMDAR activity by pharmacological approach can reverse age-associated impairment of synaptic function. Functional properties of many important proteins, including NMDAR, can be modulated by redox status via key regulatory sites, especially the crucial cysteine residues.…”

Section: Introductionmentioning

confidence: 99%

“…Synaptic plasticity, especially the long-term potentiation (LTP) in hippocampus, is widely considered as a key cellular mechanism underlying learning and memory. Generally, many studies have revealed that an impairment of hippocampal LTP usually occurs in aged animals, and this kind of impairment is thought to be the basis of AAMI (Watson et al, 2002;Mothet et al, 2006;Boric et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

Yang

Long

et al. 2010

Aging Cell

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SummaryDeficits in learning and memory accompanied by agerelated neurodegenerative diseases are closely related to the impairment of synaptic plasticity. In this study, we investigated the role of thiol redox status in the modulation of the N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) in CA1 areas of hippocampal slices. Our results demonstrated that the impaired LTP induced by aging could be reversed by acute administration of reductants that can regulate thiol redox status directly, such as dithiothreitol or b-mercaptoethanol, but not by classical anti-oxidants such as vitamin C or trolox. This repair was mediated by the recruitment of aging-related deficits in NMDAR function induced by these reductants and was mimicked by glutathione, which can restore the age-associated alterations in endogenous thiol redox status. Moreover, antioxidant prevented but failed to reverse H 2 O 2 -induced impairment of NMDARmediated synaptic plasticity. These results indicate that the restoring of thiol redox status may be a more effective strategy than the scavenging of oxidants in the treatment of pre-existing oxidative injury in learning and memory.

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Section: Discussionmentioning

confidence: 99%

Section: Modulation Of Thiol Redox Status With Reductants Directly Rementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

Yang

Long

et al. 2010

Aging Cell

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“…However, increasing evidence suggests that astrocytes also play important roles in information processing, signal transmission, and regulation of neural and synaptic plasticity (Haydon et al, 2009;Henneberger et al, 2010;Perea et al, 2009). For example, astrocytic GLTs, lactate transporters, and glial-derived neuromodulator D-serine are required for synaptic plasticity and memory (Henneberger et al, 2010;Mothet et al, 2006;Suzuki et al, 2011). Although astrocytes play an important role in synaptic plasticity and AQP4 plays a vital role in modulating astrocytic function, little is known about the potential role of AQP4 in synaptic plasticity in the amygdala.…”

Section: Introductionmentioning

confidence: 99%

Aquaporin-4 Deficiency Impairs Synaptic Plasticity and Associative Fear Memory in the Lateral Amygdala: Involvement of Downregulation of Glutamate Transporter-1 Expression

Wang

et al. 2012

Neuropsychopharmacol

101

105

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Astrocytes are implicated in information processing, signal transmission, and regulation of synaptic plasticity. Aquaporin-4 (AQP4) is the major water channel in adult brain and is primarily expressed in astrocytes. A growing body of evidence indicates that AQP4 is a potential molecular target for the regulation of astrocytic function. However, little is known about the role of AQP4 in synaptic plasticity in the amygdala. Therefore, we evaluated long-term potentiation (LTP) in the lateral amygdala (LA) and associative fear memory of AQP4 knockout (KO) and wild-type mice. We found that AQP4 deficiency impaired LTP in the thalamo-LA pathway and associative fear memory. Furthermore, AQP4 deficiency significantly downregulated glutamate transporter-1 (GLT-1) expression and selectively increased NMDA receptor (NMDAR)-mediated EPSCs in the LA. However, low concentration of NMDAR antagonist reversed the impairment of LTP in KO mice. Upregulating GLT-1 expression by chronic treatment with ceftriaxone also reversed the impairment of LTP and fear memory in KO mice. These findings imply a role for AQP4 in synaptic plasticity and associative fear memory in the amygdala by regulating GLT-1 expression.

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Molecular determinants of D‐serine‐mediated gliotransmission: From release to function

Oliet

Mothet

2006

Glia

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Since the late 80s, it is recognized that functional activation of N-methyl D-aspartate receptors (NMDARs) requires the binding of both glutamate and glycine. However, the surprising discovery that the wrong isomer of serine, D-serine, is present in mammals has profoundly challenged this dogmatic model of NMDARs activation. Indeed, there are accumulating evidence indicating that D-serine is the endogenous ligand for the glycine modulatory binding site in many brain areas. D-Serine is synthesized in glial cells by serine racemase (SR) and released upon activation of glutamate receptors. Here, we will provide an overview of recent findings on the molecular and cellular mechanisms involved in the synthesis and release of this gliotransmitter. We will also emphasize the function of this novel messenger in regulating synaptic excitatory transmission and plasticity in different brain areas. Because it fulfils all criteria for a gliotransmitter, D-serine regulatory action on glutamatergic transmission further illustrates the emerging concept of the "tripartite synapse".

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A critical role for the glial‐derived neuromodulator d‐serine in the age‐related deficits of cellular mechanisms of learning and memory

Cited by 146 publications

References 36 publications

Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

Aquaporin-4 Deficiency Impairs Synaptic Plasticity and Associative Fear Memory in the Lateral Amygdala: Involvement of Downregulation of Glutamate Transporter-1 Expression

Molecular determinants of D‐serine‐mediated gliotransmission: From release to function

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