Deep brain stimulation facilitates memory in a model of Alzheimer’s disease

2010 ◽  
Vol 1 (2) ◽  
Author(s):  
Isabel Arrieta-Cruz ◽  
Constantine Pavlides ◽  
Giulio Pasinetti
Keyword(s):  
Short Term Memory ◽  
Hippocampal Slices ◽  
In Vivo Studies ◽  
Short Term ◽  
Term Memory ◽  
Ca1 Region ◽  
Secretase Activity ◽  
Tgcrnd8 Mice ◽  
Deep Brain

AbstractBased on evidence suggesting that deep brain stimulation (DBS) may promote certain cognitive processes, we have been interested in developing DBS as a means of mitigating memory and learning impairments in Alzheimer’s disease (AD). In this study we used an animal model of AD (TgCRND8 mice) to determine the effects of high-frequency stimulation (HFS) on non-amyloidogenic α-secretase activity and DBS in short-term memory. We tested our hypothesis using hippocampal slices (in vitro studies) from TgCRND8 mice to evaluate whether HFS increases α-secretase activity (non-amyloidogenic pathway) in the CA1 region. In a second set of experiments, we performed in vivo studies to evaluate whether DBS in midline thalamic region re-establishes hippocampal dependent short-term memory in TgCRND8 mice. The results showed that application of HFS to isolated hippocampal slices significantly increased synaptic plasticity in the CA1 region and promoted a 2-fold increase of non-amyloidogenic α-secretase activity, in comparison to low frequency stimulated controls from TgCRND8 mice. In the in vivo studies, DBS treatment facilitated acquisition memory in TgCRND8 mice, in comparison to their own baseline before treatment. These results provide evidence that DBS could enhance short-term memory in a mouse model of AD by increasing synaptic transmission and α-secretase activity in the CA1 region of hippocampus.

scholarly journals Deep brain stimulation in midline thalamic region facilitates synaptic transmission and short-term memory in a mouse model of Alzheimer’s disease

2010 ◽  
Vol 1 (3) ◽  
Author(s):  
Isabel Arrieta-Cruz ◽  
Constantine Pavlides ◽  
Giulio Pasinetti
Keyword(s):  
Short Term Memory ◽  
Hippocampal Slices ◽  
In Vivo Studies ◽  
Short Term ◽  
Term Memory ◽  
Ca1 Region ◽  
Secretase Activity ◽  
Tgcrnd8 Mice ◽  
Thalamic Region

AbstractBased on evidence suggesting that deep brain stimulation (DBS) may promote certain cognitive processes, we have been interested in developing DBS as a means of mitigating memory and learning impairments in Alzheimer’s disease (AD). In this study we used an animal model of AD (TgCRND8 mice) to determine the effects of high-frequency stimulation (HFS) on non-amyloidogenic α-secretase activity and DBS in short-term memory. We tested our hypothesis using hippocampal slices (in vitro studies) from TgCRND8 mice to evaluate whether HFS increases α-secretase activity (non-amyloidogenic pathway) in the CA1 region. In a second set of experiments, we performed in vivo studies to evaluate whether DBS in midline thalamic region re-establishes hippocampal dependent short-term memory in TgCRND8 mice. The results showed that application of HFS to isolated hippocampal slices significantly increased synaptic plasticity in the CA1 region and promoted a 2-fold increase of non-amyloidogenic α-secretase activity, in comparison to low frequency stimulated controls from TgCRND8 mice. In the in vivo studies, DBS treatment facilitated acquisition of object recognition memory in TgCRND8 mice, in comparison to their own baseline before treatment. These results provide evidence that DBS could enhance short-term memory in the CA1 region of hippocampus in a mouse model of AD.

scholarly journals Increased Calbindin D28k Expression via Long-Term Alternate-Day Fasting Does Not Protect against Ischemia-Reperfusion Injury: A Focus on Delayed Neuronal Death, Gliosis and Immunoglobulin G Leakage

2021 ◽  
Vol 22 (2) ◽  
pp. 644
Author(s):  
Hyejin Sim ◽  
Tae-Kyeong Lee ◽  
Yeon Ho Yoo ◽  
Ji Hyeon Ahn ◽  
Dae Won Kim ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Pyramidal Neurons ◽  
Short Term Memory ◽  
Forebrain Ischemia ◽  
Short Term ◽  
Term Memory ◽  
Transient Forebrain Ischemia ◽  
Ca1 Pyramidal Neurons ◽  
Ca1 Region ◽  
Calbindin D28k

Calbindin-D28k (CB), a calcium-binding protein, mediates diverse neuronal functions. In this study, adult gerbils were fed a normal diet (ND) or exposed to intermittent fasting (IF) for three months, and were randomly assigned to sham or ischemia operated groups. Ischemic injury was induced by transient forebrain ischemia for 5 min. Short-term memory was examined via passive avoidance test. CB expression was investigated in the Cornu Ammonis 1 (CA1) region of the hippocampus via western blot analysis and immunohistochemistry. Finally, histological analysis was used to assess neuroprotection and gliosis (microgliosis and astrogliosis) in the CA1 region. Short-term memory did not vary significantly between ischemic gerbils with IF and those exposed to ND. CB expression was increased significantly in the CA1 pyramidal neurons of ischemic gerbils with IF compared with that of gerbils fed ND. However, the CB expression was significantly decreased in ischemic gerbils with IF, similarly to that of ischemic gerbils exposed to ND. The CA1 pyramidal neurons were not protected from ischemic injury in both groups, and gliosis (astrogliosis and microgliosis) was gradually increased with time after ischemia. In addition, immunoglobulin G was leaked into the CA1 parenchyma from blood vessels and gradually increased with time after ischemic insult in both groups. Taken together, our study suggests that IF for three months increases CB expression in hippocampal CA1 pyramidal neurons; however, the CA1 pyramidal neurons are not protected from transient forebrain ischemia. This failure in neuroprotection may be attributed to disruption of the blood–brain barrier, which triggers gliosis after ischemic insults.

Restitution and adaptation measurements for the estimate of short-term cardiac action potential memory: comparison of five human ventricular models

EP Europace ◽  
2019 ◽  
Vol 21 (10) ◽  
pp. 1594-1602
Author(s):  
Massimiliano Zaniboni ◽  
Francesca Cacciani
Keyword(s):  
Steady State ◽  
Action Potential ◽  
Short Term Memory ◽  
Computational Study ◽  
Numerical Models ◽  
Cardiac Action Potential ◽  
Short Term ◽  
Term Memory ◽  
Cardiac Action

Abstract Aims This computational study refines our recently published pacing protocol to measure short-term memory (STM) of cardiac action potential (AP), and apply it to five numerical models of human ventricular AP. Methods and results Several formulations of electrical restitution (ER) have been provided over the years, including standard, beat-to-beat, dynamic, steady-state, which make it difficult to compare results from different studies. We discuss here the notion of dynamic ER (dER) by relating it to its steady-state counterpart, and propose a pacing protocol based on dER to measure STM under periodically varying pacing cycle length (CL). Under high and highly variable-pacing rate, all models develop STM, which can be measured over the entire sequence by means of dER. Short-term memory can also be measured on a beat-to-beat basis by estimating action potential duration (APD) adaptation after clamping CL constant. We visualize STM as a phase shift between action potential (AP) parameters over consecutive cycles of CL oscillations, and show that delay between CL and APD oscillation is nearly constant (around 92 ms) in the five models, despite variability in their intrinsic AP properties. Conclusion dER, as we define it and together with other approaches described in the study, provides an univocal way to measure STM under extreme cardiac pacing conditions. Given the relevance of AP memory for repolarization dynamics and stability, STM should be considered, among other usual biomarkers, to validate and tune cardiac AP models. The possibility of extending the method to in vivo cellular and whole organ models can also be profitably explored.

scholarly journals 7-O-Esters of taxifolin with pronounced and overadditive effects in neuroprotection, anti-neuroinflammation, and amelioration of short-term memory impairment in vivo

Redox Biology ◽  
2020 ◽  
Vol 29 ◽  
pp. 101378 ◽  
Author(s):  
Sandra Gunesch ◽  
Matthias Hoffmann ◽  
Carolina Kiermeier ◽  
Wolfgang Fischer ◽  
Antonio F.M. Pinto ◽  
...  
Keyword(s):  
Memory Impairment ◽  
Short Term Memory ◽  
Short Term ◽  
Term Memory

scholarly journals A Single Brief Burst Induces GluR1-dependent Associative Short-term Potentiation: A Potential Mechanism for Short-term Memory

2010 ◽  
Vol 22 (11) ◽  
pp. 2530-2540 ◽  
Author(s):  
Martha A. Erickson ◽  
Lauren A. Maramara ◽  
John Lisman
Keyword(s):  
Knockout Mice ◽  
Short Term Memory ◽  
Long Term Potentiation ◽  
Dual Process ◽  
Short Term ◽  
Model Learning ◽  
Term Memory ◽  
Term Potentiation

Recent work showed that short-term memory (STM) is selectively reduced in GluR1 knockout mice. This raises the possibility that a form of synaptic modification dependent on GluR1 might underlie STM. Studies of synaptic plasticity have shown that stimuli too weak to induce long-term potentiation induce short-term potentiation (STP), a phenomenon that has received little attention. Here we examined several properties of STP and tested the dependence of STP on GluR1. The minimal requirement for inducing STP was examined using a test pathway and a conditioning pathway. Several closely spaced stimuli in the test pathway, forming a single brief burst, were sufficient to induce STP. Thus, STP is likely to be induced by the similar bursts that occur in vivo. STP induction is associative in nature and dependent on the NMDAR. STP decays with two components, a fast component (1.6 ± 0.26 min) and a slower one (19 ± 6.6 min). To test the role of GluR1 in STP, experiments were conducted on GluR1 knockout mice. We found that STP was greatly reduced. These results, taken together with the behavioral work of D. Sanderson et al. [Sanderson, D., Good, M. A., Skelton, K., Sprengel, R., Seeburg, P. H., Nicholas, J., et al. Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: Evidence for a dual-process memory model. Learning and Memory, 2009], provide genetic evidence that STP is a likely mechanism of STM.

scholarly journals A β-secretase modulator decreases Tau pathology and preserves short-term memory in a mouse model of neurofibrillary degeneration

2021 ◽  
Author(s):  
Marie Tautou ◽  
Sabiha Eddarkaoui ◽  
Florian Descamps ◽  
Paul-Emmanuel Larchanche ◽  
Melanie Dumoulin ◽  
...  
Keyword(s):  
Nitrogen Atom ◽  
Mouse Model ◽  
Short Term Memory ◽  
Tau Pathology ◽  
Short Term ◽  
Term Memory ◽  
Transgenic Model ◽  
Structure Activity ◽  
Inflammatory Processes

A structure-activity relationship has enabled us to identify two molecules, MAGS02-14 and PEL24-199, sharing a β-secretase modulatory effect but having or not a lysosomotropic activity, respectively. More importantly, MAGS02-14 and PEL24-199 only differ from each other by a single nitrogen atom. However, which of the lysosomotropic and/or β-secretase modulating activities is necessary for the pharmacological effect in vivo remains ill-defined. To address this question, the THY-Tau22 transgenic model of NFD was treated for 6 weeks in a curative paradigm and short-term memory, Tau burden, and inflammatory processes were studied. PEL24-199, possessing only the β-secretase modulatory activity, was shown to restore the short-term memory and to reduce NFD. This effect was associated with reduced phosphorylation of Tau, increased phosphatase expression, and a decrease of astrogliosis. Our results, therefore, suggest that the lysosomotropic activity may be dispensable for the effect on both Aβ and Tau pathologies.

scholarly journals Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory

2018 ◽  
Vol 115 (31) ◽  
pp. E7398-E7407 ◽  
Author(s):  
Joanna M. Gould ◽  
Phoebe J. Smith ◽  
Chris J. Airey ◽  
Emily J. Mort ◽  
Lauren E. Airey ◽  
...  
Keyword(s):  
Brain Development ◽  
Short Term Memory ◽  
Fetal Brain ◽  
Late Gestation ◽  
Adult Offspring ◽  
Short Term ◽  
Altered Expression ◽  
Term Memory

Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

scholarly journals A ß-Secretase Modulator Decreases Tau Pathology and Preserves Short-Term Memory in a Mouse Model of Neurofibrillary Degeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Marie Tautou ◽  
Sabiha Eddarkaoui ◽  
Florian Descamps ◽  
Paul-Emmanuel Larchanché ◽  
Jamal El Bakali ◽  
...  
Keyword(s):  
Mouse Model ◽  
Short Term Memory ◽  
Tau Pathology ◽  
Short Term ◽  
Pharmacological Activities ◽  
Term Memory ◽  
Inflammatory Processes ◽  
Orthogonal Methods ◽  
Chemical Formulas

Identifying which among several in cellulo pharmacological activities is necessary for the proper in vivo activity is essential for further drug development against Alzheimer’s disease pathophysiological processes. An in-depth structure–activity relationship–based study has been carried out, and two molecules, named MAGS02-14 and PEL24-199, that share a ß-secretase modulatory effect associated or not to a lysosomotropic activity in cellulo have been identified. In terms of chemical formulas, MAGS02-14 and PEL24-199 only differ from each other by a single nitrogen atom. The study aimed to elucidate the in vivo pharmacological effects of lysosomotropic and/or the ß-secretase modulatory activity in a tau pathology mouse model. To address this question, the THY-Tau22 transgenic model of tauopathy was treated with both compounds for 6 weeks in a curative paradigm. Short-term memory, tau burden, and inflammatory processes were analyzed using orthogonal methods, and PEL24-199, but not MAGS02-14, was shown to restore the short-term memory and reduce the neurofibrillary degenerating process. These effects were associated with a reduced phosphorylation of tau, an increased phosphatase expression, and decreased astrogliosis. Our results, therefore, suggest that the lysosomotropic activity may be nonessential for the effect on tau pathology.

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