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Background: Individuals at 80 years of age or above with exceptional memory are considered SuperAgers (SA), an operationalized definition of successful cognitive aging. SA showed increased thickness and altered functional connectivity in the anterior cingulate cortex as a neurobiological signature. However, their metabolic alterations are yet to be uncovered., Objective: Herein, a metabolic (FDG-PET), amyloid (PIB-PET), and functional (fMRI) analysis of SA were conducted., Methods: Ten SA, ten age-matched older adults (C80), and ten cognitively normal middle-aged (C50) adults underwent cognitive testing and multimodal neuroimaging examinations. Anterior and posterior regions of the cingulate cortex and hippocampal areas were primarily examined, then subregions of anterior cingulate were segregated., Results: The SA group showed increased metabolic activity in the left and right subgenual anterior cingulate cortex (sACC, p < 0.005 corrected, bilateral) and bilateral hippocampi (right: p < 0.0005 and left: p < 0.005, both corrected) as compared to that in the C80 group. Amyloid deposition was above threshold in 30% of SA and C80 (p > 0.05). The SA group also presented decreased connectivity between right sACC and posterior cingulate (p < 0.005, corrected) as compared to that of the C80 group., Conclusion: These results support the key role of sACC and hippocampus in SA, even in the presence of amyloid deposition. It also suggests that sACC may be used as a potential biomarker in older adults for exceptional memory ability. Further longitudinal studies measuring metabolic biomarkers may help elucidate the interaction between these areas in the cognitive aging process.

Peptide YY (PYY) belongs to the neuropeptide Y (NPY) family, which also includes the pancreatic polypeptide (PP) and NPY. PYY is secreted by the intestinal L cells, being present in the blood stream in two active forms capable of crossing the blood brain barrier, PYY (1-36) and its cleavage product, PYY (3-36). PYY is a selective agonist for the Y2 receptor (Y2R) and these receptors are abundant in the hippocampus. Here we investigated the mechanisms by which PYY (3-36) regulates intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in hippocampal neurons by employing a calcium imaging technique in hippocampal cultures. Alterations in [Ca 2+ ] i were detected by changes in the Fluo-4 AM reagent emission. PYY (3-36) significantly increased [Ca 2+ ] from the concentration of 10 -11 M as compared to the controls (infusion of HEPES-buffered solution (HBS) solution alone). The PYY (3-36)-increase in [Ca 2+ ] i remained unchanged even in Ca 2+ -free extracellular solutions. Sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase pump (SERCA pump) inhibition partially prevent the PYY (3-36)-increase of [Ca 2+ ] i and inositol 1,4,5-triphosphate receptor (IP3R) inhibition also decreased the PYY (3-36)-increase of [Ca 2+ ] i . Taken together, our data strongly suggest that PYY (3-36) mobilizes calcium from the neuronal endoplasmic reticulum (ER) stores towards the cytoplasm. Next, we showed that PYY (3-36) inhibited high K + -induced increases of [Ca 2+ ] i , suggesting that PYY (3-36) could also act by activating G-protein coupled inwardly rectifying potassium K + channels. Finally, the co-infusion of the Y2 receptor (Y2R) antagonist BIIE0246 with PYY (3-36) abolished the [Ca 2+ ] i increase induced by the peptide, suggesting that PYY (3-36)-induced [Ca 2+ ] i increase in hippocampal neurons occurs via Y2Rs., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Introduction: In temporal lobe epilepsy (TLE), about 30% of the patients do not achieve adequate pharmacologic control of refractory crises, and surgery becomes an alternative. In ablative interventions, neuropsychologic testing of memory is a crucial step. However, evaluations of the right hippocampal functions have not been consistent., Aim: To assess the hippocampal function in remote orientation and visuospatial memory in patients with refractory temporal epilepsy., Methods: A controlled study of patients with left (LTLE) or right (RTLE) TLE. The subjects were submitted to a neuropsychologic evaluation through the Route Learning Test and the Childhood Home Test in the preoperative period. The statistical analysis was performed using the Kruskal-Wallis, analysis of variance, χ, and Mann-Whitney U tests., Results: There was no significant difference in performance in the remote visuospatial memory (as measured by the Childhood Home Test) across the groups (LTLE, RTLE, and control). Concerning the spatial orientation memory, however, there was a significant difference between the LTLE and controls as compared with the RTLE group (P<0.001), the latter showing a poorer performance., Conclusions: The study suggests that spatial orientation memory relies on the integrity of the right hippocampus. Nevertheless, further studies are necessary to confirm this hypothesis.

All five subtypes of muscarinic acetylcholine receptors (mAChR; M(1)-M(5)) are expressed in the hippocampus, where they are involved both in cognitive functions and in synaptic plasticity, such as long-term potentiation (LTP). Muscarinic toxins (MTs) are small proteins from mamba snake venoms that display exquisite discrimination between mAChRs. MT1 acts as an agonist at M(1) and an antagonist at M(4) receptors, with similar affinities for both. MT3, the most selective antagonist available for M(4) receptors, infused into the CA1 region immediately after training caused amnesia in the rat, indicating the participation of M(4) receptors in memory consolidation. Our goal was to investigate the participation of M(4) receptor in neurotransmission at the hippocampal Schaffer collaterals-CA1 synapses. Two different preparations were used: 1) field potential recordings in freshly prepared rat hippocampal slices with high-frequency stimulation to induce potentiation and 2) whole-cell voltage clamp in cultured hippocampal organotypic slices with paired stimuli. In preparation 1, a dose of MT3 that was previously shown to cause amnesia blocked LTP; the nonselective antagonist scopolamine blocked LTP without affecting basal transmission, although it was depressed with higher concentration. In preparation 2, basal transmission was decreased and LTP induction was prevented by an MT3 concentration that would bind mainly to M(4) receptors. Although M(1) receptors appeared to modulate transmission positively at these excitatory synapses, M(1) activation concomitant with M(4) blockade (by MT1) only allowed a brief, short-term potentiation. Accordingly, M(4) blockade by MT3 strongly supports a permissive role of M(4) receptors and suggests their necessary participation in synaptic plasticity at these synapses., ((c) 2008 Wiley-Liss, Inc.)

Lateralization of memory by functional MRI (fMRI) may be helpful for surgical planning related to the medial temporal lobe (MTL). Most fMRI memory studies have calculated lateralization indices (LI) in the MTL from suprathreshold voxels only, but the selection of threshold remains highly arbitrary. We hypothesized that LIs could be reliably extracted from the distribution of voxels encompassing all positive T statistical values, each weighted by their own statistical significance. We also hypothesized that patient LIs that are two or more standard deviations (SD) away from the control group mean LI may be more clinically relevant than LIs that are not compared to control group. Thirteen healthy subjects had memory fMRI, and five epilepsy patients had both fMRI and the intracarotid amobarbital procedure (IAP). The fMRI task consisted of encoding patterns, scenes, and words. We found that normal subjects' LIs extracted from whole weighted statistical distributions tended to lateralize to the left for words, to the right for patterns, and intermediately for scenes, consistent with previous research. Weighted LIs were less variable than those calculated from suprathreshold voxels only. Using this approach, all patients had fMRI memory lateralizations consistent with IAP results. The weighted LIs provided a more clear-cut distinction of patients from the normal group (in terms of SDs from the group mean) than the suprathreshold voxel count approach. Our results suggest that using weighted distributions can be a useful strategy for assessing memory lateralization by fMRI in the MTL.

Long-term potentiation (LTP) has a long history as putative mechanism of memory formation, specially in the hippocampus, a structure essential for memory formation. Endocannabinoids are one of the endogenous systems that modulate this plasticity event: the activation of hippocampal CB1 receptors may inhibit local GABA release. Here, we have studied both (1) the role of the selective CB1 antagonist AM251 upon LTP induction in a hippocampal slice preparation, and (2) the effect of its intrahippocampal administration in the step-down inhibitory avoidance (IA) and the open field habituation tasks (OF). Standard extracellular electrophysiology techniques were used to record field excitatory postsynaptic potentials from the dendritic region of CA1 neurons in response to a high frequency stimulation of Schaffer's collaterals; a micropipette ejected 0.2 microM of AM251 (in DMSO/PBS) 2 min before the stimulus: LTP was induced and lasted more than 30 min in the control, but not in the AM251-treated group. Immediately after training, either in IA (footshock, 0.5 mA) or OF, animals received a bilateral infusion of 0.55 or 5.5 ng/side of AM251 or its vehicle in the CA1 region, and test was performed 24 h later. AM251 has caused a significative decrease in the test step-down latency when compared to the control group, but no differences were detected in the OF task, including the number of crossings, i.e., there were no motor effects. The LTP supression could be caused by AM251 acting over GABAergic interneurons that modulate the LTP-bearing glutamatergic neurons. Endocanabinoids would then be the natural dis-inhibitors of local plasticity in the dorsal hippocampus, and the amnestic action of AM251 would be due to a disruption of this endogenous modulatory system.

Object: The aim of this study was to compare seizure and memory outcome in patients with medically refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS) treated using an anterior temporal lobectomy (ATL) or a selective amygdalohippocampectomy (SA)., Methods: Surgical outcome data were prospectively collected for 2 to 11 years in 161 consecutive patients with MTLE/ HS. Eighty patients underwent an ATL and 81 an SA. Seizure control achieved with each technique was compared using the Engel classification scheme. Postoperative memory testing was performed in 86 patients (53%). At the last follow up, 72% of the patients who had undergone an ATL (mean follow up 6.7 years) and 71% of those who had undergone an SA (mean follow up 4.5 years) were seizure free (Engle Class IA). Estimated survival in patients in Engel Classes I, IA, and I and II combined did not differ between the two surgical techniques. Preoperatively, 58% of the patients had verbal memory scores one standard deviation (SD) below the normal mean. One third of the patients with preoperative scores in the normal range worsened after surgery, although this outcome was not related to the surgical technique. In contrast, one third of those whose preoperative scores were less than -1 SD experienced improvement after surgery. Nine (18%) of the 50 patients whose left side had been surgically treated improved their verbal memory scores by more than one SD. Seven (78%) of these nine underwent an SA (p = 0.05)., Conclusions: Both ATL and SA can lead to similar favorable seizure control in patients with MTLE/HS. Preliminary data suggest that postoperative verbal memory scores may improve in patients who undergo selective resection of a sclerotic hippocampus in the dominant temporal lobe.

We analyzed the effect of the acylpolyaminetoxin JSTX-3 on the epileptogenic discharges induced by perfusion of human hippocampal slices with artificial cerebrospinal fluid lacking Mg2+ or N-methyl-D-aspartate. Hippocampi were surgically removed from patients with refractory medial temporal lobe epilepsy, sliced in the surgical room and taken to the laboratory immersed in normal artificial cerebrospinal fluid. Epileptiform activity was induced by perfusion with Mg2+-free artificial cerebrospinal fluid or by iontophoretically applied N-methyl-D-aspartate and intracellular and field recordings of CA1 neurons were performed. The ictal-like discharges induced by Mg2+-free artificial cerebrospinal fluid and N-methyl-D-aspartate were blocked by incubation with JSTX-3. This effect was similar to that obtained with the N-methyl-D-aspartate receptor antagonist DL (-)2-amino-5 phosphonovaleric acid. Our findings suggest that in human hippocampal neurons, the antiepileptic effect of JSTX-3 is mediated by its action on N-methyl-D-aspartate receptor.

Unlabelled: Hippocampal sclerosis (HS) is the commonest pathology in epileptic patients undergoing temporal lobe epilepsy surgery. Beside, there are an increased density of corpora amylacea (CA) founded in 6 to 63% of those cases., Objective: verify the presence of CA and the clinical correlates of their occurrence in a consecutive series of patients undergoing temporal surgery with diagnosis of HS., Method: We reviewed 72 hippocampus specimens from January 1997 to July 2000. Student's t test for independent, samples, ANOVA and Tukey test were performed for statistical analysis., Results: CA were found in 35 patients (49%), whose mean epilepsy duration (28.7 years) was significantly longer than that group of patients without CA (19.5 years, p=0.001). Besides, when CA were found, duration was also significantly correlated with distribution within hippocampus: 28.7 years with diffuse distribution of CA, 15.4 with exclusively subpial and 17.4 years with distribution subpial plus perivascular (p=0.001)., Conclusion: Our findings corroborate the presence of CA in patients with HS and suggest that a longer duration of epilepsy correlate with a more distribution of CA in hippocampus.