Spermidine‐induced improvement of memory involves a cross‐talk between protein kinases C and A

Guerra, Gustavo Petri; Mello, Carlos Fernando; Bochi, Guilherme Vargas; Pazini, Andréia Martini; Rosa, Michelle Melgarejo da; Ferreira, Juliano; Rubin, Maribel Antonello

doi:10.1111/j.1471-4159.2012.07778.x

Cited by 28 publications

(10 citation statements)

References 92 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conversely, there is a large body of evidence indicating that the promnesic effects of polyamines involve the activation of NMDA receptors, which have been critically implicated in learning and memory processes [ 36 , 40 , 44 , 45 , 69 - 71 ]. In the current study, ifenprodil, a noncompetitive GluN2B-containing NMDA receptor antagonist, not only impaired the consolidation of the memory of novel object recognition task, but also reversed (at a dose that did not alter memory per se in our study) the improving effect of spermine on the memory of LPS-treated animals, supporting a role for NMDA receptors in this effect of spermine [ 72 - 74 ].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous reports have indicated that polyamines improve memory in several tasks and attenuate memory deficits induced by different amnesic agents [ 32 - 41 ]. In fact, agonists and antagonists of the polyamine binding site at the NMDA receptor respectively facilitate and impair memory in various tasks [ 33 , 34 , 36 , 39 , 40 , 42 , 43 ], and the sequential activation of protein kinase C (PKC) and PKA/CREB (protein kinase A/cAMP response element-binding protein) pathways in the hippocampus has been implicated in the promnesic effect of polyamines [ 44 , 45 ]. However, it has recently been described that interruption of the NMDA receptor modulation by polyamines reverses Aβ 25–35 -induced memory impairment in mice in a novel object recognition task [ 46 ], suggesting that the role of polyamines in memory may vary in physiological and pathological conditions.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Spermine reverses lipopolysaccharide-induced memory deficit in mice

Frühauf

Ineu

Tomazi

et al. 2015

J Neuroinflammation

View full text Add to dashboard Cite

BackgroundLipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines improve memory in various cognitive tasks, we hypothesized that spermine administration reverses LPS-induced memory deficits in an object recognition task in mice. The involvement of the polyamine binding site at the N-methyl-D-aspartate (NMDA) receptor and cytokine production in the promnesic effect of spermine were investigated.MethodsAdult male mice were injected with LPS (250 μg/kg, intraperitoneally) and spermine (0.3 to 1 mg/kg, intraperitoneally) or ifenprodil (0.3 to 10 mg/kg, intraperitoneally), or both, and their memory function was evaluated using a novel object recognition task. In addition, cortical and hippocampal cytokines levels were measured by ELISA four hours after LPS injection.ResultsSpermine increased but ifenprodil decreased the recognition index in the novel object recognition task. Spermine, at doses that did not alter memory (0.3 mg/kg, intraperitoneally), reversed the cognitive impairment induced by LPS. Ifenprodil (0.3 mg/kg, intraperitoneally) reversed the protective effect of spermine against LPS-induced memory deficits. However, spermine failed to reverse the LPS-induced increase of cortical and hippocampal cytokine levels.ConclusionsSpermine protects against LPS-induced memory deficits in mice by a mechanism that involves GluN2B receptors.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Spermine reverses lipopolysaccharide-induced memory deficit in mice

Frühauf

Ineu

Tomazi

et al. 2015

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…They inhibit AC-cAMP-PKA signaling and activate phospholipase C-diacyl glycerol-PKC signaling. The well-documented interactions between PKA and PKC signaling pathways (9,13,41,50) indicate that A 1 R-PKC activation decreases the activation threshold of PKA by GLP-1. In addition, PKC directly activates AC (4,54) and phosphorylates CREB in cultured rat neurons (31,55).…”

Section: Discussionmentioning

confidence: 99%

An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury

Ihara

Asanuma

Yamazaki

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

zuki N, Kitakaze M. An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 308: H1287-H1297, 2015. First published March 7, 2015; doi:10.1152/ajpheart.00835.2014.-Dipeptidyl peptidase 4 (DPP4) inhibitors suppress the metabolism of the potent antihyperglycemic hormone glucagon-like peptide-1 (GLP-1). DPP4 was recently shown to provide cardioprotection through a reduction of infarct size, but the mechanism for this remains elusive. Known interactions between DPP4 and adenosine deaminase (ADA) suggest an involvement of adenosine signaling in DPP4 inhibitor-mediated cardioprotection. We tested whether the protective mechanism of the DPP4 inhibitor alogliptin against myocardial ischemia-reperfusion injury involves GLP-1-and/or adenosine-dependent signaling in canine hearts. In anesthetized dogs, the coronary artery was occluded for 90 min followed by reperfusion for 6 h. A 4-day pretreatment with alogliptin reduced the infarct size from 43.1 Ϯ 2.5% to 17.1 Ϯ 5.0% without affecting collateral flow and hemodynamic parameters, indicating a potent antinecrotic effect. Alogliptin also suppressed apoptosis as demonstrated by the following analysis: 1) reduction in the Bax-to-Bcl2 ratio; 2) cytochrome c release, 3) an increase in Bad phosphorylation in the cytosolic fraction; and 4) terminal deoxynucleotidyl transferase dUTP nick end labeling assay. This DPP4 inhibitor did not affect blood ADA activity or adenosine concentrations. In contrast, the nonselective adenosine receptor blocker 8-(p-sulfophenyl)theophylline (8SPT) completely blunted the effect of alogliptin. Alogliptin did not affect Erk1/2 phosphorylation, but it did stimulate phosphorylation of Akt, glycogen synthase kinase-3␤, and cAMP response element-binding protein (CREB). Only 8SPT prevented alogliptin-induced CREB phosphorylation. In conclusion, the DPP4 inhibitor alogliptin suppresses ischemia-reperfusion injury via adenosine receptor-and CREB-dependent signaling pathways. dipeptidyl peptidase 4 inhibitor; ischemia-reperfusion injury; myocardial infarction; cardioprotection; adenosine GLUCAGON-LIKE PEPTIDE-1 (GLP-1) is mostly known as a potent antihyperglycemic hormone secreted by intestinal cells to stimulate glucose-dependent insulin secretion from pancreatic beta cells. Once in circulation, GLP-1 is rapidly metabolized by dipeptidyl peptidase 4 (DPP4). Therefore, GLP-1 analogs and DPP4 inhibitors are commonly prescribed for the treatment of diabetes mellitus (6, 11). DPP4 inhibitors also exert extrapancreatic effects in the brain, stomach, and heart (39). However, the mechanisms by which they mediate these effects remain largely unknown. Several reports showed that DPP4 inhibitors limit the infarct size after ischemia-reperfusion in the heart (15, 51), but the extent of their beneficial effects remains controversial (7,52). Recently, several reports have indicated that DPP4 forms a complex with adenosin...

show abstract

“…In addition, Guerra et al (2011Guerra et al ( , 2012 showed that protein kinase A (PKA) and PKC inhibitors prevent the facilitatory effect of spermidine on the memory of an inhibitory avoidance task. Accordingly, they also prevented the spermidine-induced phosphorylation of PKC, PKA, and CREB in the hippocampus (Guerra et al 2011(Guerra et al , 2012. Therefore, the effect of spermidine on memory consolidation seems to involve a sequence of biochemical events that are triggered by NMDA receptors, followed by the activation of NOS and the sequential activation of PKC and PKA/CREB signaling in the hippocampus of rats.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

“…The needles were left in place for additional 60 sec to minimize backflow. Doses were selected based on previous studies (Guerra et al 2012) and pilot experiments.…”

Section: Surgerymentioning

confidence: 99%

Spermidine-induced improvement of reconsolidation of memory involves calcium-dependent protein kinase in rats

et al. 2015

View full text Add to dashboard Cite

In this study, we determined whether the calcium-dependent protein kinase (PKC) signaling pathway is involved in the improvement of fear memory reconsolidation induced by the intrahippocampal administration of spermidine in rats. Male Wistar rats were trained in a fear conditioning apparatus using a 0.4-mA footshock as an unconditioned stimulus. Twenty-four hours after training, animals were re-exposed to the apparatus in the absence of shock (reactivation session). Immediately after the reactivation session, spermidine (2 -200 pmol/site), the PKC inhibitor 3-[1-(dimethylaminopropyl)indol-3-yl]-4-(indol-3-yl) maleimide hydrochloride (GF 109203X, 0.3 -30 pg/site), the antagonist of the polyamine-binding site at the NMDA receptor, arcaine (0.2 -200 pmol/site), or the PKC activator phorbol 12-myristate 13-acetate (PMA, 0.02 -2 nmol/site) was injected. While the post-reactivation administration of spermidine (20 and 200 pmol/site) and PMA (2 nmol/site) improved memory reconsolidation, GF 109203X (1, 10, and 30 pg/site) and arcaine (200 pmol/site) impaired it. GF 109203X (0.3 pg/site) impaired memory reconsolidation in the presence of spermidine (200 pmol/site). PMA (0.2 nmol/site) prevented the arcaine (200 pmol/site)-induced impairment of memory reconsolidation. Anisomycin (2 mg/site) also impaired memory reconsolidation in the presence of spermidine (200 pmol/site). Drugs had no effect when they were administered in the absence of reactivation. These results suggest that the spermidine-induced enhancement of memory reconsolidation involves PKC activation.

show abstract

Spermidine‐induced improvement of memory involves a cross‐talk between protein kinases C and A

Cited by 28 publications

References 92 publications

Spermine reverses lipopolysaccharide-induced memory deficit in mice

Spermine reverses lipopolysaccharide-induced memory deficit in mice

An interaction between glucagon-like peptide-1 and adenosine contributes to cardioprotection of a dipeptidyl peptidase 4 inhibitor from myocardial ischemia-reperfusion injury

Spermidine-induced improvement of reconsolidation of memory involves calcium-dependent protein kinase in rats

Contact Info

Product

Resources

About