Brain temperature in healthy and diseased conditions: A review on the special implications of MRS for monitoring brain temperature

Brain temperature determines not only an individual's cognitive functionality but also the prognosis and mortality rates of many brain diseases. More specifically, brain temperature not only changes in response to different physiological events like yawning and stretching, but also plays a significant pathophysiological role in a number of neurological and neuropsychiatric illnesses. Here, we have outlined the function of brain hyperthermia in both diseased and healthy states, focusing particularly on the amyloid beta aggregation in Alzheimer's disease

Chemogenetic inhibition of MCH neurons does not alter memory performance in mice

Memory storage in the brain is one of the most extensively studied subjects in neuroscience. However, due to the highly complex structure of the memory-related systems in the brain, the mystery remains unsolved. Consolidation is one of the most important parts of the memory process, and one that can be affected by numerous neurodegenerative diseases. Hypothalamic melanin-concentrating hormone (MCH) neuronal activity has been of particular interest to researchers in terms of the association between sleep, neurodegenerative diseases, and memory consolidation. We used Pmch-Cre animals to investigate the role of MCH neuronal activity in memory consolidation. In order to observe the differences in memory consolidation, we chemogenetically inhibited MCH neurons using the DREADD method and measured hippocampus-dependent memory performance with a novel object recognition test applicable to early memory impairment in Alzheimer's disease. Our results revealed no significant improvement or worsening with MCH inhibition, suggesting that the role of MCH should now be evaluated in a wider setting

The effect of resveratrol on sphingosine-1 and oxidative/ nitrosative stress in an experimental heart ischemia reperfusion model

Objectives: Resveratrol (RSV) is a natural polyphenolic compound showing significant antioxidant effects. In this study, we aimed to investigate the effects of resveratrol on the sphingosine-1-phosphate (S1P) and oxidative stress biomarkers in hearth ischemia-reperfusion (I/R). Materials and Methods: The biochemical and histopathological effects of RSV on cardiac ischemia-reperfusion injury were investigated through ELISA- and light microscope. Results: We observed statistically significant differences between the treatment group and the control group in terms of malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities (p<0.05). Histopathologically, we also observed decreased Polymorphonuclear Leucocyte (PMNL) infiltration, myocardial edema, miyositolysis in the treatment group compared to the I/R and sham groups. Conclusion: Resveratrol may play an important role in cardiac I/R injury through its anti-inflammatory and antioxidant effects which were biochemically and histopathologically confirmed in the present study

Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: A randomised, double-blinded, placebo-controlled phase-II trial

Background: Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases

Background: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by activating mitochondrial metabolism. Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation. Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats. Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs.PoLiMeR Innovative Training Network ; SNIC ; ScandiBio Therapeutics ; ScandiBio Therapeutics and Knut ; Knut och Alice Wallenbergs Stiftels

Non-ideal distortion effects in single and two layer modulation schemes

Telsiz haberleşme sistemlerinde verici ve alıcı devreleri ile kanalda meydana gelen ideal olmayan etkiler gönderilen sinyalin faz ve genliğinde ideal olmayan bozulmalara yol açmaktadır. Verici devrelerindeki güç yükselteçleri ve darbe şekillendirmesi, kanalda meydana gelen sönümlenme ve gecikmeler, alıcı devrelerindeki eşzamanlama hataları ile kestirim hataları gibi etmenler başarım oranını etkilemektedir. Bu çalışma kapsamında, bir telsiz haberleşme sisteminin fiziksel katmanında bir uçtan bir uca meydana gelebilecek ideal olmayan etmenler modellenmiştir. Her aşamada sinyal iletiminin başarımı, sistemde kullanılabilecek tüm tek ve çift katmanlı kiplemeler için bit/sembol/paket hata oranları cinsinden incelenmiş, en iyi başarımı sağlayacak parametre, model ve yöntemler belirlenmiştir. Sonuçta, baştan sona bir sistem tasarımı ve benzetimi, ara aşamalarda belirlenen en anlamlı parametreler kullanılarak, gerçekleştirilmiştir. Bu çalışmada elde edilen veriler ile bir telsiz haberleşme sisteminin fiziksel katmanında meydana gelen bozulum, tek ve çift katmanlı kiplemeler için bit/sembol/paket hata oranları üzerindeki etkilerini gösteren bir kütüphane oluşturulmuştur. Böylece, tezin kapsamında olduğu projenin kavramsal tasarımı için gerekli olan parametrelerin elde edilmesi ve geleceğe yönelik bilgi birikimi oluşturulması amaçlanmıştır.In wireless communication systems, non-ideal effects in transmitter and receiver circuits and in the channel cause non-ideal distortions in the phase and amplitude of transmitted signal. The power amplifiers and pulse shaping in the transmitter side, the attenuation and delays in the channel, synchronization errors and estimation errors in the receiver side are effecting performance of the system. In this work, the non-ideal effects that can occur throughout physical layer of a wireless communication system are modeled. In every stage, performance of signal transmission is studied in terms of bit/symbol/packet error rates of all single and hierarchical modulations that can be used in the system, and the best performance parameters, models and methods are determined. Finally, an overall system design and simulation that is consistent with the studied stages is performed. With the data acquired by this work, a library that comprises bit/symbol/packet error rates of the single and hierarchical modulations in the pyhsical layer of a wireless communications system is formed. Thus, the required parameters for the conseptual design of the project that this thesis is in the scope of and fund of knowledge for future is aimed

The therapeutic role of minocycline in Parkinson's disease

Minocycline, a semisynthetic tetracycline-derived antibiotic, has been shown to exert anti-apoptotic, anti-inflammatory, and antioxidant effects. Furthermore, there is rapidly growing evidence suggesting that minocycline may have some neuroprotective activity in various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease (PD), Huntington's disease, and multiple sclerosis. In this perspective review, we summarize the preclinical and clinical findings suggesting the neuroprotective role of minocycline in PD. © 2019 Cankaya S, Cankaya B, Kilic U, Kilic E, Yulug B. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission

A different view on the pathophysiology of Parkinson’s disease: A descendent neurochemical hypothesis?

It has been already shown that Parkinson’s disease (PD) is characterized by a prominent degeneration in substantia nigra (SN)neurons. Growing evidence suggests that there is a latent period of PD associated with slight non-motor findings such as olfactorydys function (Dickson et al., 2018). However, the potential biomarker role of olfactory dysfunction in PD has been a topic of great interest in the last years (Raskin et al., 1990; Dicksonet al., 2018). The classical hypothesis of Braak suggests that PD begins as a synucleinopathy in the lower brainstem or in the olfactorybulb (OB) that progresses rostrally to the SN and amygdalato cause parkinsonism at a later stage of the disease (Burkeet al., 2008). However, Braak’s hypothesis should be cautiously interpreted since this scheme is not based on the distribution of neuronal cell loss, but on the distribution of the accumulation of abnormal α-synuclein aggregates which leaves unanswered how it relates to the progression of neurochemical changes

Quantitative evaluation of brain volumes in drug-free major depressive disorder using MRI-Cloud method

Background Quantitative analysis of the high-resolution T1-weighted images provides useful markers to measure anatomical changes during brain degeneration related to major depressive disorder (MDD). However, there are controversial findings regarding these volume alterations in MDD indicating even to increased volumes in some specific regions in MDD patients. Methods This study is a case-controlled study including 23 depression patients and 15 healthy subject person and 20-38 years of age, who have been treated at the Neurology and Psychiatry Department here. We compared specific anatomic regions between drug-free MDD patients and control group through MRI-Cloud, which is a novel brain imaging method that enables to analyze multiple brain regions simultaneously. Results We have found that frontal, temporal, and parietal hemispheric volumes and middle frontal gyrus, inferior frontal gyrus, superior parietal gyrus, cingulum-hippocampus, lateral fronto-orbital gyrus, superior temporal gyrus, superior temporal white matter, middle temporal gyrus subanatomic regions were significantly reduced bilaterally in MDD patients compared to the control group, while striatum, amygdala, putamen, and nucleus accumbens bilaterally increased in MDD group compared to the control group suggesting that besides the heterogeneity among studies, also comorbid factors such as anxiety and different personal traits could be responsible for these discrepant results. Conclusion Our study gives a strong message that depression is associated with altered structural brain volumes, especially, in drug-free and first-episode MDD patients who present with similar duration and severity of depression while the role of demographic and comorbid risk factors should not be neglected.Alanya Alaaddin Keykubat Universit

Melatonin affects the release of exosomes and tau-content in in vitro amyloid-beta toxicity model

Background: Recent studies have been revealed that oxidative damage is the main cause of aging and age-related neurodegenerative diseases like Alzheimer's disease (AD). Melatonin is secreted from the pineal gland and its secretion has been found to be altered in AD. In the last decade the role of exosomes in spreading toxic proteins and inducing the propagation of diseases like AD has been discussed. However, it is not known how melatonin affects the amount of exosomes released from the cells and the content of the exosomes.Objective: Herein, we investigated the possible role of melatonin treatment in the releasing of exosomes and exosomal tau content in an in vitro A beta toxicity model.Method: SH-SY5Y cell line was used. The optimum concentration of A beta was determined by cell viability and cell proliferation tests. Melatonin (100 mM) was applied before and after A beta application. Total exosomes isolated from cell culture media were immunoprecipitated. The amount of released exosomes and their tau content were analyzed by Western blots.Results: Our data demonstrated for the first time that melatonin treatment clearly affected the amount of released exosomes. It would decrease the amyloid beta load and toxicity by inhibiting exosome release. We also demonstated that melatonin also affected the level of tau carried by exosomes depending on whether melatonin was applied before or after A beta application.Conclusion: It is considered that the effect of melatonin in the release of exosomes and exosomal tau content would contribute the development of therapeutic strategies in AD and related disorders