Peripheral Lipid Signatures, Metabolic Dysfunction, and Pathophysiology in Schizophrenia Spectrum Disorders.

Metabolic dysfunction is commonly observed in schizophrenia spectrum disorders (SSDs). The causes of metabolic comorbidity in SSDs are complex and include intrinsic or biological factors linked to the disorder, which are compounded by antipsychotic (AP) medications. The exact mechanisms underlying SSD pathophysiology and AP-induced metabolic dysfunction are unknown, but dysregulated lipid metabolism may play a role. Lipidomics, which detects lipid metabolites in a biological sample, represents an analytical tool to examine lipid metabolism. This systematic review aims to determine peripheral lipid signatures that are dysregulated among individuals with SSDs (1) with minimal exposure to APs and (2) during AP treatment. To accomplish this goal, we searched MEDLINE, Embase, and PsychINFO databases in February 2024 to identify all full-text articles written in English where the authors conducted lipidomics in SSDs. Lipid signatures reported to significantly differ in SSDs compared to controls or in relation to AP treatment and the direction of dysregulation were extracted as outcomes. We identified 46 studies that met our inclusion criteria. Most of the lipid metabolites that significantly differed in minimally AP-treated patients vs. controls comprised glycerophospholipids, which were mostly downregulated. In the AP-treated group vs. controls, the significantly different metabolites were primarily fatty acyls, which were dysregulated in conflicting directions between studies. In the pre-to-post AP-treated patients, the most impacted metabolites were glycerophospholipids and fatty acyls, which were found to be primarily upregulated and conflicting, respectively. These lipid metabolites may contribute to SSD pathophysiology and metabolic dysfunction through various mechanisms, including the modulation of inflammation, cellular membrane permeability, and metabolic signaling pathways.

Exploring the potential of steel slag waste for carbon sequestration through mineral carbonation: A comparative study of blast-furnace slag and ladle slag.

Steel slag is a by-product of steelmaking which has emerged as a potential CO2 sequestration material due to its high reactivity and abundance. This research investigates the use of steel slag waste for the direct capture of carbon from air and its storage through mineral carbonation. Two abundant wastes, blast-furnace slag (BFS) and ladle slag (LS), were tested for their carbon sequestration potential, and the effects of operational parameters such as reaction time between CO2 and slag waste, temperature, liquid-solid ratio, and pressure on CO2 sequestration were determined. Quantitative and qualitative results reveal that much higher CO2 sequestration was achieved using LS compared to BFS after exposure to CO2 for 1 day at room temperature. By increasing the exposure time to four days, levels of CO2 sequestration increased gradually from 2.71% to 4.19% and 23.46%-28.21% for BFS and LS respectively. Increasing the temperature from 20 ± 2 °C to 90 ± 2 °C positively influenced CO2 sequestration in BFS, resulting in an enhancement from 3.45% to 13.21%. However, the impact on LS was insignificant, with sequestration levels rising from 27.72% to 29.90%. Moreover, better CO2 sequestration was observed for BFS than LS when the liquid-to-solid ratio increased from 3:1 to 4:1, whereupon the sequestration potential reached approximately 15% for BFS and 30% for LS at 90 ± 2 °C. Meanwhile, higher pressure reduced the sequestration potential of slag. The results of this study suggest that there is potential for scaling up the process to industrial applications and contributing to the reduction of CO2 emissions in the steelmaking industry.

Power generation from wastewater using microbial fuel cells: A review.

As the world grapples with an imminent energy crisis brought on by the depletion of nonrenewable resources, such as petroleum, the necessity for alternative and eco-friendly power sources becomes increasingly apparent. In this regard harnessing knowledge gained from natural microorganisms to produce electricity using economical substrates is a promising solution through microbial fuel cells (MFCs). Microbial fuel cells leverage microbes' catabolic abilities to break down organic matter and release electrons that are subsequently transported across an external circuit for electricity generation. This article delves into the fundamental components involved in MFC construction and explores crucial factors that impact their performance including substrate oxidation, electron transfer, and internal resistance. Additionally, it offers a comprehensive analysis of existing microbial fuel cell designs while highlighting their respective strengths and weaknesses. Finally, the article showcases cost-effective MFC models based on thorough studies conducted worldwide while illuminating potential practical applications of this renewable energy technology.

Experimental investigation of the parameters that affect droplet size and distribution for design calculations of two-phase separators.

The critical design parameter when sizing a separator is the size of oil droplets in the water phase. This study improves the design of a separator by investigating the parameters that control droplet size, frequency, and distribution. Experimental work was performed to investigate the effect of flow rates and oil layer thickness on these parameters. Experiments were performed using a transparent laboratory separator to allow the measurement of droplet properties. The Design of the Experiment (DOE) method with the Taguchi analysis was applied to investigate statistically if droplet properties are solely a function of the independent variables or if they interact. The findings show that the results can be modelled using Gaussian distributions. Droplet size distribution and the number of droplets produced are functions of the interaction between oil flow rate and oil pad thickness. The oil flow rate dominates the droplet size though layer thickness has a minor effect. The number of droplets (Frequency) increases with both oil and water flow rates but decreases with oil pad thickness. There are clear interactions between all variables resulting in different droplet frequencies for combined effects. The distribution of the droplet sizes is controlled by oil layer thickness, where the spread is seen to rise with thickness. However, interactions between the fluid flows and oil pad thickness give rise to different droplet distributions if either variable were changed on its own.

Fourier Transform Infrared Imaging-A Novel Approach to Monitor Bio Molecular Changes in Subacute Mild Traumatic Brain Injury.

Traumatic brain injury (TBI) can be defined as a disorder in the function of the brain after a bump, blow, or jolt to the head, or penetrating head injury. Mild traumatic brain injury (mTBI) can cause devastating effects, such as the initiation of long-term neurodegeneration in brain tissue. In the current study, the effects of mTBI were investigated on rat brain regions; cortex (Co) and corpus callosum (CC) after 24 h (subacute trauma) by Fourier transform infrared (FTIR) imaging and immunohistochemistry (IHC). IHC studies showed the formation of amyloid-ß (Aß) plaques in the cortex brain region of mTBI rats. Moreover, staining of myelin basic protein presented the shearing of axons in CC region in the same group of animals. According to FTIR imaging results, total protein and lipid content significantly decreased in both Co and CC regions in mTBI group compared to the control. Due to this significant decrease in both lipid and protein content, remarkable consistency in lipid/protein band ratio in mTBI and control group, was observed. Significant decrease in methyl content and a significant increase in olefinic content were observed in Co and CC regions of mTBI rat brain tissues. Classification amongst distinguishable groups was performed using principal component analysis (PCA) and hierarchical clustering (HCA). This study established the prospective of FTIR imaging for assessing biochemical changes due to mTBI with high sensitivity, precision and high-resolution.

Prognostic value of GRACE score for in-hospital and 6 months outcomes after non-ST elevation acute coronary syndrome.

BACKGROUND: The aim of this study was to determine the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for predicting in-hospital and 6 months mortality after non-ST elevation acute coronary syndrome (NSTE-ACS). RESULTS: In this observational study, 300 patients with NSTE-ACS of age more than 30 years were included; 16 patients died during the hospital stay (5.3%). Of 284 patients at 6 months assessment, 10 patients died (3.5%), 240 survived (84.5%), and 34 were lost to follow-up (12%) respectively. In high risk category, 10.5% of the patients died within hospital stay and 11.8% died within 6 months (p = 0.001 and p = 0.013). In univariate analysis, gender, diabetes mellitus, family history, smoking, and GRACE score were significantly associated with in-hospital mortality whereas age, obesity, dyslipidemia, and GRACE were significantly associated with 6 months mortality. After adjustment, diabetes mellitus, family history, and GRACE score remained significantly associated with in-hospital mortality (p ≤ 0.05) and age remained significantly associated with 6 months mortality. CONCLUSION: GRACE risk score has good predictive value for the prediction of in-hospital mortality and 6 months mortality among patients with NSTE-ACS.

Biomolecular alterations in acute traumatic brain injury (TBI) using Fourier transform infrared (FTIR) imaging spectroscopy.

Acute injury is one of the substantial stage post-traumatic brain injury (TBI) occurring at the moment of impact. Decreased metabolism, unregulated cerebral blood flow and direct tissue damage are triggered by acute injury. Understating the biochemical alterations associated with acute TBI is critical for brain plasticity and recovery. The objective of this study was to investigate the biochemical and molecular changes in hippocampus, corpus callosum and thalamus brain regions post-acute TBI in rats. Fourier Transform Infrared (FTIR) imaging spectroscopy were used to collect chemical images from control and 3 hrs post-TBI (Marmarou model was used for the TBI induction) rat brains and adjacent sections were treated by hematoxylin and eosin (H&E) staining to correlate with the disruption in tissue morphology and injured brain biochemistry. Our results revealed that the total lipid and total protein content decreased significantly in the hippocampus, corpus callosum and thalamus after brain injury. Reduction in lipid acyl chains (-CH2) associated with an increase in methyl (-CH3) and unsaturated lipids olefin = CH concentrations is observed. Furthermore, there is a decrease in the lipid order (disorder), which leads to an increase in acyl chain fluidity in injured rats. The results suggest acute TBI damages brain tissues mechanically rather than chemical alterations. This will help in assessing successful therapeutic strategy in order to mitigate tissue damage in acute TBI period.

Imaging Markers for the Characterization of Gray and White Matter Changes from Acute to Chronic Stages after Experimental Traumatic Brain Injury.

Despite clinical symptoms, a large majority of people with mild traumatic brain injury (TBI) have normal computed tomography (CT) and magnetic resonance imaging (MRI) scans. Therefore, present-day neuroimaging tools are insufficient to diagnose or classify low grades of TBI. Advanced neuroimaging techniques, such as diffusion-weighted and functional MRI, may yield novel biomarkers that may aid in the diagnosis of TBI. Therefore, the present study had two aims: first, to characterize the development of MRI-based measures of structural and functional changes in gray and white matter regions from acute to chronic stages after mild and moderate TBI; and second, to identify the imaging markers that can most accurately predict outcome after TBI. To these aims, 52 rats underwent serial functional (resting-state) and structural (T1-, T2-, and diffusion-weighted) MRI before and 1 h, 1 day, 1 week, 1 month and 3-4 months after mild or moderate experimental TBI. All rats underwent behavioral testing. Histology was performed in subgroups of rats at different time points. Early after moderate TBI, axial and radial diffusivities were increased, and fractional anisotropy was reduced in the corpus callosum and bilateral hippocampi, which normalized over time and was paralleled by recovery of sensorimotor function. Correspondingly, histology revealed decreased myelin staining early after TBI, which was not detected at chronic stages. No significant changes in individual outcome measures were detected after mild TBI. However, multivariate analysis showed a significant additive contribution of diffusion parameters in the distinction between control and different grades of TBI-affected brains. Therefore, combining multiple imaging markers may increase the sensitivity for TBI-related pathology.

Chronic Sodium Selenate Treatment Restores Deficits in Cognition and Synaptic Plasticity in a Murine Model of Tauopathy.

A major goal in diseases is identifying a potential therapeutic agent that is cost-effective and can remedy some, if not all, disease symptoms. In Alzheimer's disease (AD), aggregation of hyperphosphorylated tau protein is one of the neuropathological hallmarks, and Tau pathology correlates better with cognitive impairments in AD patients than amyloid-ß load, supporting a key role of tau-related mechanisms. Selenium is a non-metallic trace element that is incorporated in the brain into selenoproteins. Chronic treatment with sodium selenate, a non-toxic selenium compound, was recently reported to rescue behavioral phenotypes in tau mouse models. Here, we focused on the effects of chronic selenate application on synaptic transmission and synaptic plasticity in THY-Tau22 mice, a transgenic animal model of tauopathies. Three months with a supplement of sodium selenate in the drinking water (12 µg/ml) restored not only impaired neurocognitive functions but also rescued long-term depression (LTD), a major form of synaptic plasticity. Furthermore, selenate reduced the inactive demethylated catalytic subunit of protein phosphatase 2A (PP2A) in THY-Tau22 without affecting total PP2A.Our study provides evidence that chronic dietary selenate rescues functional synaptic deficits of tauopathy and identifies activation of PP2A as the putative mechanism.

The two faces of synaptic failure in AppNL-G-F knock-in mice.

BACKGROUND: Intensive basic and preclinical research into Alzheimer's disease (AD) has yielded important new findings, but they could not yet been translated into effective therapies. One of the reasons is the lack of animal models that sufficiently reproduce the complexity of human AD and the response of human brain circuits to novel treatment approaches. As a step in overcoming these limitations, new App knock-in models have been developed that avoid transgenic APP overexpression and its associated side effects. These mice are proposed to serve as valuable models to examine Aß-related pathology in "preclinical AD." METHODS: Since AD as the most common form of dementia progresses into synaptic failure as a major cause of cognitive deficits, the detailed characterization of synaptic dysfunction in these new models is essential. Here, we addressed this by extracellular and whole-cell patch-clamp recordings in AppNL-G-F mice compared to AppNL animals which served as controls. RESULTS: We found a beginning synaptic impairment (LTP deficit) at 3-4 months in the prefrontal cortex of AppNL-G-F mice that is further aggravated and extended to the hippocampus at 6-8 months. Measurements of miniature EPSCs and IPSCs point to a marked increase in excitatory and inhibitory presynaptic activity, the latter accompanied by a moderate increase in postsynaptic inhibitory function. CONCLUSIONS: Our data reveal a marked impairment of primarily postsynaptic processes at the level of synaptic plasticity but the dominance of a presumably compensatory presynaptic upregulation at the level of elementary miniature synaptic function.

Design and capital cost optimisation of three-phase gravity separators.

The separation of produced fluids is essential once it reaches the surface. This separation is achieved in gravity separators. The design and sizing of separators can be challenging due to the number of factors involved. Improper separator design can bottleneck and reduce the production of the entire facility. This paper describes the development of a capital cost optimisation model for sizing three phase separators. The developed model uses GRG Non-linear algorithms to determine the minimum cost associated with the construction of horizontal separators subject to four sets of constraints. A numerical sizing example was solved to provide the details associated with the model and the ease with which parameters can be varied to suit the user's needs. Finally, a spreadsheet comparison between results obtained from the developed model and four other extant models is carried out. Results indicated that the developed model predicted results within an absolute error of ±5m3 in most cases and a maximum of ±12.5m3 for very high gas flows in comparison to conventional models developed based on retention time theory.

Syndapin I Loss-of-Function in Mice Leads to Schizophrenia-Like Symptoms.

Schizophrenia is associated with cognitive and behavioral dysfunctions thought to reflect imbalances in neurotransmission systems. Recent screenings suggested that lack of (functional) syndapin I (PACSIN1) may be linked to schizophrenia. We therefore studied syndapin I KO mice to address the suggested causal relationship to schizophrenia and to analyze associated molecular, cellular, and neurophysiological defects. Syndapin I knockout (KO) mice developed schizophrenia-related behaviors, such as hyperactivity, reduced anxiety, reduced response to social novelty, and an exaggerated novel object response and exhibited defects in dendritic arborization in the cortex. Neuromorphogenic deficits were also observed for a schizophrenia-associated syndapin I mutant in cultured neurons and coincided with a lack of syndapin I-mediated membrane recruitment of cytoskeletal effectors. Syndapin I KO furthermore caused glutamatergic hypofunctions. Syndapin I regulated both AMPAR and NMDAR availabilities at synapses during basal synaptic activity and during synaptic plasticity-particularly striking were a complete lack of long-term potentiation and defects in long-term depression in syndapin I KO mice. These synaptic plasticity defects coincided with alterations of postsynaptic actin dynamics, synaptic GluA1 clustering, and GluA1 mobility. Both GluA1 and GluA2 were not appropriately internalized. Summarized, syndapin I KO led to schizophrenia-like behavior, and our analyses uncovered associated molecular and cellular mechanisms.

Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models.

Many mouse models of Alzheimer's disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reported in human studies. In other AD mouse models LTP is unaffected, but other defects in synaptic plasticity may still be present. We recently reported that THY-Tau22 transgenic mice, that overexpress human Tau protein carrying P301S and G272 V mutations and show normal LTP upon high-frequency-stimulation (HFS), develop severe changes in NMDAR mediated long-term-depression (LTD), the physiological counterpart of LTP. In the present study, we focused on putative effects of AD-related pathologies on depotentiation (DP), another form of synaptic plasticity. Using a novel protocol to induce DP in the CA1-region, we found in 11-15 months old male THY-Tau22 and APPPS1-21 transgenic mice that DP was not deteriorated by Aß pathology while significantly compromised by Tau pathology. Our findings advocate DP as a complementary form of synaptic plasticity that may help in elucidating synaptic pathomechanisms associated with different types of dementia.

Perispinal injection of a TNF blocker directed to the brain of rats alleviates the sensory and affective components of chronic constriction injury-induced neuropathic pain.

Neuropathic pain is chronic pain that follows nerve injury, mediated in the brain by elevated levels of the inflammatory protein tumor necrosis factor-alpha (TNF). We have shown that peripheral nerve injury increases TNF in the hippocampus/pain perception region, which regulates neuropathic pain symptoms. In this study we assessed pain sensation and perception subsequent to specific targeting of brain-TNF (via TNF antibody) administered through a novel subcutaneous perispinal route. Neuropathic pain was induced in Sprague-Dawley rats via chronic constriction injury (CCI), and thermal hyperalgesia was monitored for 10 days post-surgery. On day 8 following CCI and sensory pain behavior testing, rats were randomized to receive perispinal injection of TNF antibody or control IgG isotype antibody. Pain perception was assessed using conditioned place preference (CPP) to the analgesic, amitriptyline. CCI-rats receiving the perispinal injection of TNF antibody had significantly decreased CCI-induced thermal hyperalgesia the following day, and did not form an amitriptyline-induced CPP, whereas CCI-rats receiving perispinal IgG antibody experienced pain alleviation only in conjunction with i.p. amitriptyline and did form an amitriptyline-induced CPP. The specific targeting of brain TNF via perispinal delivery alleviates thermal hyperalgesia and positively influences the affective component of pain. PERSPECTIVE: This study presents a novel route of drug administration to target central TNF for treatment of neuropathic pain. Targeting central TNF through perispinal drug delivery could potentially be a more efficient and sustained method to treat patients with neuropathic pain.

Age-associated cholesterol reduction triggers brain insulin resistance by facilitating ligand-independent receptor activation and pathway desensitization.

In the brain, insulin plays an important role in cognitive processes. During aging, these faculties decline, as does insulin signaling. The mechanism behind this last phenomenon is unclear. In recent studies, we reported that the mild and gradual loss of cholesterol in the synaptic fraction of hippocampal neurons during aging leads to a decrease in synaptic plasticity evoked by glutamate receptor activation and also by receptor tyrosine kinase (RTK) signaling. As insulin and insulin growth factor activity are dependent on tyrosine kinase receptors, we investigated whether the constitutive loss of brain cholesterol is also involved in the decay of insulin function with age. Using long-term depression (LTD) induced by application of insulin to hippocampal slices as a read-out, we found that the decline in insulin function during aging could be monitored as a progressive impairment of insulin-LTD. The application of a cholesterol inclusion complex, which donates cholesterol to the membrane and increases membrane cholesterol levels, rescued the insulin signaling deficit and insulin-LTD. In contrast, extraction of cholesterol from hippocampal neurons of adult mice produced the opposite effect. Furthermore, in vivo inhibition of Cyp46A1, an enzyme involved in brain cholesterol loss with age, improved insulin signaling. Fluorescence resonance energy transfer (FRET) experiments pointed to a change in receptor conformation by reduced membrane cholesterol, favoring ligand-independent autophosphorylation. Together, these results indicate that changes in membrane fluidity of brain cells during aging play a key role in the decay of synaptic plasticity and cognition that occurs at this late stage of life.

The Anti-Tumor Agent Sodium Selenate Decreases Methylated PP2A, Increases GSK3ßY216 Phosphorylation, Including Tau Disease Epitopes and Reduces Neuronal Excitability in SHSY-5Y Neurons.

Selenium application as sodium selenate was repeatedly shown to have anti-carcinogenic properties by increasing levels of the serine/ threonine protein phosphatase 2A (PP2A) in cancer cells. PP2A has a prominent role in cell development, homeostasis, and in neurons regulates excitability. PP2A, GSK3ß and Tau reside together in a complex, which facilitates their interaction and (dys)-function as has been reported for several neurological disorders. In this study we recorded maximum increase in total PP2A at 3 µM sodium selenate in a neuron cell line. In conjunction with these data, whole-cell electrophysiological studies revealed that this concentration had maximum effect on membrane potentials, conductance and currents. Somewhat surprisingly, the catalytically active form, methylated PP2A (mePP2A) was significantly decreased. In close correlation to these data, the phosphorylation state of two substrate proteins, sensitive to PP2A activity, GSK3ß and Tau were found to be increased. In summary, our data reveal that sodium selenate enhances PP2A levels, but reduces catalytic activity of PP2A in a dose dependent manner, which fails to reduce Tau and GSK3ß phosphorylation under physiological conditions, indicating an alternative route in the rescue of cell pathology in neurological disorders.

Brain insulin response and peripheral metabolic changes in a Tau transgenic mouse model.

Accumulation of hyper-phosphorylated and aggregated Tau proteins is a neuropathological hallmark of Alzheimer's Disease (AD) and Tauopathies. AD patient brains also exhibit insulin resistance. Whereas, under normal physiological conditions insulin signaling in the brain mediates plasticity and memory formation, it can also regulate peripheral energy homeostasis. Thus, in AD, brain insulin resistance affects both cognitive and metabolic changes described in these patients. While a role of Aß oligomers and APOE4 towards the development of brain insulin resistance emerged, contribution of Tau pathology has been largely overlooked. Our recent data demonstrated that one of the physiological function of Tau is to sustain brain insulin signaling. We postulated that under pathological conditions, hyper-phosphorylated/aggregated Tau is likely to lose this function and to favor the development of brain insulin resistance. This hypothesis was substantiated by observations from patient brains with pure Tauopathies. To address the potential link between Tau pathology and brain insulin resistance, we have evaluated the brain response to insulin in a transgenic mouse model of AD-like Tau pathology (THY-Tau22). Using electrophysiological and biochemical evaluations, we surprisingly observed that, at a time when Tau pathology and cognitive deficits are overt and obvious, the hippocampus of THY-Tau22 mice exhibits enhanced response to insulin. In addition, we demonstrated that the ability of i.c.v. insulin to promote body weight loss is enhanced in THY-Tau22 mice. In line with this, THY-Tau22 mice exhibited a lower body weight gain, hypoleptinemia and hypoinsulinemia and finally a metabolic resistance to high-fat diet. The present data highlight that the brain of transgenic Tau mice exhibit enhanced brain response to insulin. Whether these observations are ascribed to the development of Tau pathology, and therefore relevant to human Tauopathies, or unexpectedly results from the Tau transgene overexpression is debatable and discussed.

Single mild traumatic brain injury results in transiently impaired spatial long-term memory and altered search strategies.

Mild traumatic brain injury (mTBI) can lead to diffuse neurophysical damage as well as cognitive and affective alterations. The nature and extent of behavioral changes after mTBI are still poorly understood and how strong an impact force has to be to cause long-term behavioral changes is not yet known. Here, we examined spatial learning acquisition, retention and reversal in a Morris water maze, and assessed search strategies during task performance after a single, mild, closed-skull traumatic impact referred to as "minimal" TBI. Additionally, we investigated changes in conditioned learning in a contextual fear-conditioning paradigm. Results show transient deficits in spatial memory retention, which, although limited, are indicative of deficits in long-term memory reconsolidation. Interestingly, minimal TBI causes animals to relapse to less effective search strategies, affecting performance after a retention pause. Apart from cognitive deficits, results yielded a sub-acute, transient increase in freezing response after fear conditioning, with no increase in baseline behavior, an indication of a stronger affective reaction to aversive stimuli after minimal TBI or greater susceptibility to stress. Furthermore, western blot analysis showed a short-term increase in hippocampal GFAP expression, most likely indicating astrogliosis, which is typically related to injuries of the central nervous system. Our findings provide evidence that even a very mild impact to the skull can have detectable consequences on the molecular, cognitive and affective-like level. However, these effects seemed to be very transient and reversible.

AMP-Activated Protein Kinase Is Essential for the Maintenance of Energy Levels during Synaptic Activation.

Although the brain accounts for only 2% of the total body mass, it consumes the most energy. Neuronal metabolism is tightly controlled, but it remains poorly understood how neurons meet their energy demands to sustain synaptic transmission. Here we provide evidence that AMP-activated protein kinase (AMPK) is pivotal to sustain neuronal energy levels upon synaptic activation by adapting the rate of glycolysis and mitochondrial respiration. Furthermore, this metabolic plasticity is required for the expression of immediate-early genes, synaptic plasticity, and memory formation. Important in this context, in neurodegenerative disorders such as Alzheimer disease, dysregulation of AMPK impairs the metabolic response to synaptic activation and processes that are central to neuronal plasticity. Altogether, our data provide proof of concept that AMPK is an essential player in the regulation of neuroenergetic metabolic plasticity induced in response to synaptic activation and that its deregulation might lead to cognitive impairments.

Fourier-Transform Infrared Imaging Spectroscopy and Laser Ablation -ICPMS New Vistas for Biochemical Analyses of Ischemic Stroke in Rat Brain.

Objective: Stroke is the main cause of adult disability in the world, leaving more than half of the patients dependent on daily assistance. Understanding the post-stroke biochemical and molecular changes are critical for patient survival and stroke management. The aim of this work was to investigate the photo-thrombotic ischemic stroke in male rats with particular focus on biochemical and elemental changes in the primary stroke lesion in the somatosensory cortex and surrounding areas, including the corpus callosum. Materials and Methods: FT-IR imaging spectroscopy and LA-ICPMS techniques examined stroke brain samples, which were compared with standard immunohistochemistry studies. Results: The FTIR results revealed that in the lesioned gray matter the relative distribution of lipid, lipid acyl and protein contents decreased significantly. Also at this locus, there was a significant increase in aggregated protein as detected by high-levels Aß1-42. Areas close to the stroke focus experienced decrease in the lipid and lipid acyl contents associated with an increase in lipid ester, olefin, and methyl bio-contents with a novel finding of Aß1-42 in the PL-GM and L-WM. Elemental analyses realized major changes in the different brain structures that may underscore functionality. Conclusion: In conclusion, FTIR bio-spectroscopy is a non-destructive, rapid, and a refined technique to characterize oxidative stress markers associated with lipid degradation and protein denaturation not characterized by routine approaches. This technique may expedite research into stroke and offer new approaches for neurodegenerative disorders. The results suggest that a good therapeutic strategy should include a mechanism that provides protective effect from brain swelling (edema) and neurotoxicity by scavenging the lipid peroxidation end products.