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.

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.

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 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 E47 regulates hematopoietic stem cell proliferation and energetics but not myeloid lineage restriction

Blood ◽  
2011 ◽  
Vol 117 (13) ◽  
pp. 3529-3538 ◽  
Author(s):  
Qi Yang ◽  
Brandt Esplin ◽  
Lisa Borghesi
Keyword(s):  
Energy Metabolism ◽  
Myeloid Differentiation ◽  
Short Term ◽  
Hematopoietic Stem ◽  
Altered Expression ◽  
Helix Loop Helix ◽  
Multipotent Progenitors

Abstract The immune system is replenished by self-renewing hematopoietic stem cells (HSCs) that produce multipotent progenitors (MPPs) with little renewal capacity. E-proteins, the widely expressed basic helix-loop-helix transcription factors, contribute to HSC and MPP activity, but their specific functions remain undefined. Using quantitative in vivo and in vitro approaches, we show that E47 is dispensable for the short-term myeloid differentiation of HSCs but regulates their long-term capabilities. E47-deficient progenitors show competent myeloid production in short-term assays in vitro and in vivo. However, long-term myeloid and lymphoid differentiation is compromised because of a progressive loss of HSC self-renewal that is associated with diminished p21 expression and hyperproliferation. The activity of E47 is shown to be cell-intrinsic. Moreover, E47-deficient HSCs and MPPs have altered expression of genes associated with cellular energy metabolism, and the size of the MPP pool but not downstream lymphoid precursors in bone marrow or thymus is rescued in vivo by antioxidant. Together, these observations suggest a role for E47 in the tight control of HSC proliferation and energy metabolism, and demonstrate that E47 is not required for short-term myeloid differentiation.

scholarly journals Altered expression of Armet and Mrlp51 in the oocyte, preimplantation embryo, and brain of mice following oocyte in vitro maturation but postnatal brain development and cognitive function are normal

Reproduction ◽  
2011 ◽  
Vol 142 (3) ◽  
pp. 401-408 ◽  
Author(s):  
Ning Wang ◽  
Liya Wang ◽  
Fang Le ◽  
Qitao Zhan ◽  
Yingming Zheng ◽  
...  
Keyword(s):  
Brain Development ◽  
Early Stage ◽  
Suppressive Subtractive Hybridization ◽  
Control Group ◽  
Newborn Mice ◽  
Altered Expression ◽  
Developmental Potential ◽  
The Brain

Despite the efforts to recapitulate the follicle environment, oocytes from in vitro maturation (IVM) have poorer developmental potential than those matured in vivo and the effects on the resultant offspring are of concern. The aim of this study was to determine altered gene expression in oocytes following IVM and to evaluate the expression of the arginine rich, mutated in early stage of tumors gene (Armet) and mitochondrial ribosomal protein L51 (Mrpl51) in embryos and brains of fetal/postnatal mice and the brain development of IVM offspring. An IVM mouse model was established while oocytes matured in vivo were used as the controls. Suppressive subtractive hybridization (SSH) and RT-PCR/western blot were used to analyze the differential expression of genes/proteins between IVM and the control group. HE staining and water maze were used to assess the histological changes in brain tissue and cognition of the offspring. The rates of fertilization, cleavage, and live birth were significantly decreased in IVM group. Thirteen genes were upregulated in IVM oocytes compared with the control, including Armet and Mrpl51. The higher level of Armet in IVM oocytes was retained in brain of newborn mice, which could be related to the upregulation of activating transcription factor 6 (Atf6) and X-box binding protein 1 (Xbp1), while Mrpl51 was expressed normally in brain of postnatal mice. No significant differences were detected in brain weight, neuronal counts, and the cognition in the offspring between the two groups. The present results suggested that IVM could affect the pregnancy outcome and the Armet and Mrpl51 gene/protein expression. The change in Armet expression lasted while the change of Mrpl51 disappeared after birth. However, the brain development of the offspring seemed to be unaffected by IVM.

scholarly journals Placental serotonin signaling, pregnancy outcomes, and regulation of fetal brain development†

2019 ◽  
Vol 102 (3) ◽  
pp. 532-538 ◽  
Author(s):  
Cheryl S Rosenfeld
Keyword(s):  
Brain Development ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Mammalian Species ◽  
Fetal Brain ◽  
Primary Source ◽  
Junctional Zone ◽  
Paracrine Effects ◽  
Fetal Brain Development

Abstract The placenta is a transient organ but essential for the survival of all mammalian species by allowing for the exchanges of gasses, nutrients, and waste between maternal and fetal placenta. In rodents and humans with a hemochorial placenta, fetal placenta cells are susceptible to pharmaceutical agents and other compounds, as they are bathed directly in maternal blood. The placenta of mice and humans produce high concentrations of serotonin (5-HT) that can induce autocrine and paracrine effects within this organ. Placental 5-HT is the primary source of this neurotransmitter for fetal brain development. Increasing number of pregnant women at risk of depression are being treated with selective serotonin-reuptake inhibitors (SSRIs) that bind to serotonin transporters (SERT), which prevents 5-HT binding and cellular internalization, allowing for accumulation of extracellular 5-HT available to bind to 5-HT(2A) receptor (5-HT(2A)R). In vitro and in vivo findings with SSRI or pharmacological blockage of the 5-HT(2A)R reveal disruptions of 5-HT signaling within the placenta can affect cell proliferation, division, and invasion. In SERT knockout mice, numerous apoptotic trophoblast cells are observed, as well as extensive pathological changes within the junctional zone. Collective data suggest a fine equilibrium in 5-HT signaling is essential for maintaining normal placental structure and function. Deficiencies in placental 5-HT may also result in neurobehavioral abnormalities. Evidence supporting 5-HT production and signaling within the placenta will be reviewed. We will consider whether placental hyposerotonemia or hyperserotonemia results in similar pathophysiological changes in the placenta and other organs. Lastly, open ended questions and future directions will be explored.

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.

δ Opioid Receptor Inverse Agonists and their In Vivo Pharmacological Effects

2020 ◽  
Vol 20 (31) ◽  
pp. 2889-2902 ◽  
Author(s):  
Shigeto Hirayama ◽  
Hideaki Fujii
Keyword(s):  
Opioid Receptor ◽  
Short Term Memory ◽  
Inverse Agonist ◽  
Pharmacological Effects ◽  
Short Term ◽  
Inverse Agonists ◽  
Δ Opioid Receptor ◽  
Receptor Inverse Agonist

The discovery of δ opioid receptor inverse agonist activity induced by ICI-174,864, which was previously reported as an δ opioid receptor antagonist, opened the door for the investigation of inverse agonism/constitutive activity of the receptors. Various peptidic or non-peptidic δ opioid receptor inverse agonists have since been developed. Compared with the reports dealing with in vitro inverse agonist activities of novel compounds or known compounds as antagonists, there have been almost no publications describing the in vivo pharmacological effects induced by a δ opioid receptor inverse agonist. After the observation of anorectic effects with the δ opioid receptor antagonism was discussed in the early 2000s, the short-term memory improving effects and antitussive effects have been very recently reported as possible pharmacological effects induced by a δ opioid receptor inverse agonist. In this review, we will survey the developed δ opioid receptor inverse agonists and summarize the possible in vivo pharmacological effects by δ opioid receptor inverse agonists. Moreover, we will discuss important issues involved in the investigation of the in vivo pharmacological effects produced by a δ opioid receptor inverse agonist.

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