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Brain Metabolism: Tissue-Specific Features, Role in Cognitive Functions and Pathological Changes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 7292

Special Issue Editor

Prof. Dr. Victoria Bunik

E-Mail Website
Guest Editor
1. Department of Biokinetics, A. N. Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, 119234 Moscow, Russia
2. Department of Biochemistry, Sechenov University, 105043 Moscow, Russia
3. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia
Interests: interplay between metabolism and signaling; intracellular compartmentation; metabolic regulation; multienzyme complexes of 2-oxo acid dehydrogenases; organization of metabolic pathways; protein structure–function relationship; supramolecular structures
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

This special issue is dedicated to the brain metabolism. Traditionally, the most addressed aspects in this research field are the energy production and neurotransmitter synthesis. However, there are many other biosynthetic and regulatory reactions that have specific significance for the brain function, exemplified by involvement of the brain protein synthesis into the memory formation. Nevertheless, for a long time, molecular neuroscience research has been dominated by studies of channels and receptors. Accordingly, the channels and receptors are overrepresented among the drug targets employed to fight neurological disorders. Regulation of the brain metabolic enzymes in this regard is only emerging. Identification of critical points for coupling the metabolic and neuronal oscillations represents further interesting aspect of the brain metabolism. An extremely high level of heterogeneity of the brain tissue is certainly supported by the metabolic heterogeneity, but characterization of the regional metabolism is rather fragmentary. Intracellular metabolic differences between the soma and processes of cells in neural tissue are not widely studied either. Gender-dependent differences of the brain metabolism are not properly addressed. We therefore invite the submissions to our special issue, that will develop understanding of the intracellular, regional and gender-dependent features of the brain metabolism, focusing on intimate links between the metabolism and functions of central nervous system in health and disease.

Prof. Dr. Victoria Bunik
Guest Editor

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Keywords

  • neurotransmitter
  • brain metabolic enzyme
  • heterogeneity of the brain tissue
  • central nervous system

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Published Papers (3 papers)

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Research

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30 pages, 5458 KiB  
Article
Pentylenetetrazole-Induced Seizures Are Increased after Kindling, Exhibiting Vitamin-Responsive Correlations to the Post-Seizures Behavior, Amino Acids Metabolism and Key Metabolic Regulators in the Rat Brain
by Vasily A. Aleshin, Anastasia V. Graf, Artem V. Artiukhov, Alexander L. Ksenofontov, Lev G. Zavileyskiy, Maria V. Maslova and Victoria I. Bunik
Int. J. Mol. Sci. 2023, 24(15), 12405; https://doi.org/10.3390/ijms241512405 - 3 Aug 2023
Cited by 3 | Viewed by 2857
Abstract
Epilepsy is characterized by recurrent seizures due to a perturbed balance between glutamate and GABA neurotransmission. Our goal is to reveal the molecular mechanisms of the changes upon repeated challenges of this balance, suggesting knowledge-based neuroprotection. To address this goal, a set of [...] Read more.
Epilepsy is characterized by recurrent seizures due to a perturbed balance between glutamate and GABA neurotransmission. Our goal is to reveal the molecular mechanisms of the changes upon repeated challenges of this balance, suggesting knowledge-based neuroprotection. To address this goal, a set of metabolic indicators in the post-seizure rat brain cortex is compared before and after pharmacological kindling with pentylenetetrazole (PTZ). Vitamins B1 and B6 supporting energy and neurotransmitter metabolism are studied as neuroprotectors. PTZ kindling increases the seizure severity (1.3 fold, p < 0.01), elevating post-seizure rearings (1.5 fold, p = 0.03) and steps out of the walls (2 fold, p = 0.01). In the kindled vs. non-kindled rats, the post-seizure p53 level is increased 1.3 fold (p = 0.03), reciprocating a 1.4-fold (p = 0.02) decrease in the activity of 2-oxoglutarate dehydrogenase complex (OGDHC) controlling the glutamate degradation. Further, decreased expression of deacylases SIRT3 (1.4 fold, p = 0.01) and SIRT5 (1.5 fold, p = 0.01) reciprocates increased acetylation of 15 kDa proteins 1.5 fold (p < 0.01). Finally, the kindling abrogates the stress response to multiple saline injections in the control animals, manifested in the increased activities of the pyruvate dehydrogenase complex, malic enzyme, glutamine synthetase and decreased malate dehydrogenase activity. Post-seizure animals demonstrate correlations of p53 expression to the levels of glutamate (r = 0.79, p = 0.05). The correlations of the seizure severity and duration to the levels of GABA (r = 0.59, p = 0.05) and glutamate dehydrogenase activity (r = 0.58, p = 0.02), respectively, are substituted by the correlation of the seizure latency with the OGDHC activity (r = 0.69, p < 0.01) after the vitamins administration, testifying to the vitamins-dependent impact of the kindling on glutamate/GABA metabolism. The vitamins also abrogate the correlations of behavioral parameters with seizure duration (r 0.53–0.59, p < 0.03). Thus, increased seizures and modified post-seizure behavior in rats after PTZ kindling are associated with multiple changes in the vitamin-dependent brain metabolism of amino acids, linked to key metabolic regulators: p53, OGDHC, SIRT3 and SIRT5. Full article
(This article belongs to the Special Issue Brain Metabolism: Tissue-Specific Features, Role in Cognitive Functions and Pathological Changes)
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10 pages, 2399 KiB  
Communication
Chronic Administration of Non-Constitutive Proteasome Inhibitor Modulates Long-Term Potentiation and Glutamate Signaling-Related Gene Expression in Murine Hippocampus
by Alexander Maltsev, Sergei Funikov, Alexander Rezvykh, Ekaterina Teterina, Vladimir Nebogatikov, Alexander Burov, Natalia Bal, Aleksey Ustyugov, Vadim Karpov and Alexey Morozov
Int. J. Mol. Sci. 2023, 24(9), 8172; https://doi.org/10.3390/ijms24098172 - 3 May 2023
Viewed by 1398
Abstract
Proteasomes degrade most intracellular proteins. Several different forms of proteasomes are known. Little is known about the role of specific proteasome forms in the central nervous system (CNS). Inhibitors targeting different proteasome forms are used in clinical practice and were shown to modulate [...] Read more.
Proteasomes degrade most intracellular proteins. Several different forms of proteasomes are known. Little is known about the role of specific proteasome forms in the central nervous system (CNS). Inhibitors targeting different proteasome forms are used in clinical practice and were shown to modulate long-term potentiation (LTP) in hippocampal slices of untreated animals. Here, to address the role of non-constitutive proteasomes in hippocampal synaptic plasticity and reveal the consequences of their continuous inhibition, we studied the effect of chronic administration of the non-constitutive proteasome inhibitor ONX-0914 on the LTP induced by two different protocols: tetanic stimulation and theta-burst stimulation (TBS). Both the tetanus- and TBS-evoked potentiation contribute to the different forms of hippocampal-dependent memory and learning. Field-excitatory postsynaptic potentials (fEPSPs) in hippocampal slices from control animals and animals treated with DMSO or ONX-0914 were compared. LTP induced by the TBS was not affected by ONX-0914 administration; however, chronic injections of ONX-0914 led to a decrease in fEPSP slopes after tetanic stimulation. The observed effects correlated with differential expression of genes involved in synaptic plasticity, glutaminergic synapse, and synaptic signaling. Obtained results indicate that non-constitutive proteasomes are likely involved in the tetanus-evoked LTP, but not the LTP occurring after TBS, supporting the relevance and complexity of the role of specific proteasomes in synaptic plasticity, memory, and learning. Full article
(This article belongs to the Special Issue Brain Metabolism: Tissue-Specific Features, Role in Cognitive Functions and Pathological Changes)
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Review

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23 pages, 5522 KiB  
Review
Synthetic Thioesters of Thiamine: Promising Tools for Slowing Progression of Neurodegenerative Diseases
by Lucien Bettendorff
Int. J. Mol. Sci. 2023, 24(14), 11296; https://doi.org/10.3390/ijms241411296 - 10 Jul 2023
Cited by 5 | Viewed by 2622
Abstract
Thiamine (vitamin B1) is essential for the brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. The synthetic thiamine prodrug, the thioester benfotiamine (BFT), has been extensively studied and has beneficial effects both in rodent [...] Read more.
Thiamine (vitamin B1) is essential for the brain. This is attributed to the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. The synthetic thiamine prodrug, the thioester benfotiamine (BFT), has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has no known adverse effects and improves cognitive outcomes in patients with mild Alzheimer’s disease. In cell culture and animal models, BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. Recent in vitro studies show that another thiamine thioester, O,S-dibenzoylthiamine (DBT), is even more efficient than BFT, especially with respect to its anti-inflammatory potency, and is effective at lower concentrations. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified open thiazole ring derivatives. The identification of the active neuroprotective metabolites and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental, and psychiatric conditions. The present review aims to summarize existing data on the neuroprotective effects of thiamine thioesters and give a comprehensive account. Full article
(This article belongs to the Special Issue Brain Metabolism: Tissue-Specific Features, Role in Cognitive Functions and Pathological Changes)
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