Differential Fasting Plasma Glucose and Ketone Body Levels in GHRKO versus 3xTg-AD Mice: A Potential Contributor to Aging-Related Cognitive Status?

Cognitive function declines with age and appears to correlate with decreased cerebral metabolic rate (CMR). Caloric restriction, an antiaging manipulation that extends life-span and can preserve cognitive function, is associated with decreased glucose uptake, decreased lactate levels, and increased ketone body (KB) levels in the brain. Since the majority of brain nutrients come from the periphery, this study examined whether the capacity to regulate peripheral glucose levels and KB production differs in animals with successful cognitive aging (growth hormone receptor knockouts, GHRKOs) versus unsuccessful cognitive aging (the 3xTg-AD mouse model of Alzheimer\u27s disease). Animals were fasted for 5 hours with their plasma glucose and KB levels subsequently measured. Intriguingly, in GHRKO mice, compared to those in controls, fasting plasma glucose levels were significantly decreased while their KB levels were significantly increased. Conversely, 3xTg-AD mice, compared to controls, exhibited significantly elevated plasma glucose levels and significantly reduced plasma KB levels. Taken together, these results suggest that the capacity to provide the brain with KBs versus glucose throughout an animal\u27s life could somehow help preserve cognitive function with age, potentially through minimizing overall brain exposure to reactive oxygen species and advanced glycation end products and improving mitochondrial function

Amyloid Beta-Related Alterations to Glutamate Signaling Dynamics During Alzheimer\u27s Disease Progression.

Alzheimer’s disease (AD) ranks sixth on the Centers for Disease Control and Prevention Top 10 Leading Causes of Death list for 2016, and the Alzheimer’s Association attributes 60% to 80% of dementia cases as AD related. AD pathology hallmarks include accumulation of senile plaques and neurofibrillary tangles; however, evidence supports that soluble amyloid beta (Aβ), rather than insoluble plaques, may instigate synaptic failure. Soluble Aβ accumulation results in depression of long-term potentiation leading to cognitive deficits commonly characterized in AD. The mechanisms through which Aβ incites cognitive decline have been extensively explored, with a growing body of evidence pointing to modulation of the glutamatergic system. The period of glutamatergic hypoactivation observed alongside long-term potentiation depression and cognitive deficits in later disease stages may be the consequence of a preceding period of increased glutamatergic activity. This review will explore the Aβ-related changes to the tripartite glutamate synapse resulting in altered cell signaling throughout disease progression, ultimately culminating in oxidative stress, synaptic dysfunction, and neuronal loss

pi-/pi+ ratio in heavy ions collisions: Coulomb effect or chemical equilibration?

We calculate the pi-/pi+ ratio for Pb+Pb at CERN/SPS energies and for Au+Au at BNL/AGS energies using a (3+1) dimensional hydrodynamical model. Without consideration of Coulomb effect an enhancement of this ratio at low mt is found compatible with that observed in these experiments. Our calculations are based on previous (3+1) dimensional hydrodynamical simulations (HYLANDER), which described many other aspects of experimental data. In this model the observed enhancement is a consequence of baryon and strangeness conservation and of chemical equilibration of the system and is caused by the decay of produced hyperons, which leads to a difference in the total number of positive and negative pions as well. Based on the same approach, we also present results for the pi-/pi+ ratio for S+S (CERN/SPS) collisions, where we find a similar effect. The absence of the enhancement of the pi-/pi+ ratio in the S+S data presented by the NA44 Collaboration, if confirmed, could indicate that chemical equilibration has not yet been estabilished in this reaction.Comment: 8 pages and 2 figures, submmited to Phys. Lett. B. This reviewed version (Nov.29,1996) contains more details about the model simulated efficiency considering the experimental detection conditions. Other small modifications were mad

Comment on ``Strangeness enhancement in p+Ap+A and S+A+A interactions at energies near 200 AA GeV"

We argue that the recent analysis of strangeness production in nuclear collisions at 200 $A$ GeV/$c$ performed by Topor Pop {\it et al.} \cite{To:95} is flawed. The conclusions are based on an erroneous interpretation of the data and the numerical model results. The term ``strangeness enhancement" is used in a misleading way.Comment: 4 pages REVTEX 3.0, no figures; Comment submitted to Physical Review

Particle abundances and spectra in the hydrodynamical description of relativistic nuclear collisions with light projectiles

We show that a hydrodynamical model with continuous particle emission instead of sudden freeze out may explain both the observed strange particle and pion abundances and transverse mass spectra for light projectile at SPS energy. We found that the observed enhancement of pion production corresponds, within the context of continuous emission, to the maximal entropy production.Comment: 11 pages, 2 figure

Formation of Centauro and Strangelets in Nucleus-Nucleus Collisions at the LHC and their Identification by the ALICE Experiment

We present a phenomenological model which describes the formation of a Centauro fireball in nucleus-nucleus interactions in the upper atmosphere and at the LHC, and its decay to non-strange baryons and Strangelets. We describe the CASTOR detector for the ALICE experiment at the LHC. CASTOR will probe, in an event-by-event mode, the very forward, baryon-rich phase space 5.6 < \eta < 7.2 in 5.5 A TeV central Pb + Pb collisions. We present results of simulations for the response of the CASTOR calorimeter, and in particular to the traversal of Strangelets.Comment: 4 pages, 4 figures, to appear in the proceedings of the 26th ICR

Diet-induced insulin resistance elevates hippocampal glutamate as well as VGLUT1 and GFAP expression in AβPP/PS1 mice.

The symptomologies of Alzheimer\u27s disease (AD) develop over decades suggesting modifiable lifestyle factors may contribute to disease pathogenesis. In humans, hyperinsulinemia associated with type 2 diabetes mellitus increases the risk for developing AD and both diseases share similar age-related etiologies including amyloidogenesis. Since we have demonstrated that soluble Aβ42 elicits glutamate release, we wanted to understand how diet-induced insulin resistance alters hippocampal glutamate dynamics, which are important for memory formation and consolidation. Eight to twelve-week-old C57BL/6J and AβPP/PS1 mice were placed on either a low-fat diet or high-fat diet (HFD) for 8 months. A HFD led to significant weight increases as well as impaired insulin sensitivity, glucose tolerance, and learning in both C57BL/6J and AβPP/PS1 mice. AβPP/PS1 low-fat diet mice had elevated hippocampal basal as well as stimulus-evoked glutamate release that was further increased with consumption of a HFD. Immunohistochemistry indicated an increase in vesicular glutamate transporter 1 and glial fibrillary acidic protein density in hippocampal subregions corresponding with this elevated extracellular glutamate. While no differences in hippocampal plaque load were observed, the elevated astrogliotic response surrounding the plaques in AβPP/PS1 HFD mice may have been a compensatory mechanism to control plaque accumulation. These data support that AβPP/PS1 mice have chronically elevated extracellular glutamate that is exacerbated by a HFD and that modifiable lifestyle factors such as obesity-induced insulin resistance can contribute to AD pathogenesis. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/

Confronting particle emission scenarios with strangeness data

We show that a hadron gas model with continuous particle emission instead of freeze out may solve some of the problems (high values of the freeze out density and specific net charge) that one encounters in the latter case when studying strange particle ratios such as those by WA85. This underlines the necessity to understand better particle emission in hydrodynamics to be able to analyze data. It also re-opens the possibility of a quark-hadron transition occuring with phase equilibrium instead of explosively.Comment: 13 pages, 2 figures, to appear in Phys. Rev. Let

Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.

Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer\u27s disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer\u27s disease