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Molecular and Cellular Mechanisms of Brain Disease: Hippocampus as a Nodal Point

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 9326

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Special Issue Editor

Prof. Dr. Natalia V. Gulyaeva

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Guest Editor

1. Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia
2. Moscow Research and Clinical Center for Neuropsychiatry, Moscow 115419, Russia
Interests: adaptation; Alzheimer animal models; apoptosis; behaviour; biomarkers; cellular models; cerebral ischemia; dementia; depression; epilepsy; excitotoxicity; free radicals; glia; glucocorticoid signalin
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Dear Colleagues,

The complicated structure of the hippocampus (different subfields, septotemporal gradient) and its connections with numerous essential parts of the brain provide its key position in realizing different forms of behavioral plasticity and response to environmental factors. Notably, the dentate gyrus of the hippocampus maintains the production of new neurons throughout life.

A critical brain structure for working and spatial memory as well as for emotional behaviors in animals and humans, the hippocampus is a very plastic brain structure. However, the price for its high plasticity is its selective vulnerability to the development of pathological processes induced by numerous stress factors, as well as ischemia, seizures, head trauma, aging, etc. and mediated by signal transduction associated with stress hormones and neuroinflammation. Altered neurogenesis and damage of hippocampal neurons are suggested to be involved in the onset of numerous brain illnesses, particularly mental disorders and neurodegenerative diseases. Over the past decade, it has become clear that hippocampal malfunction is a nodal point for comorbidity between neurological and psychiatric diseases, in particular cognitive disturbances, epilepsy, and affective disorders.

This Special Issue of the International Journal of Molecular Sciences focuses on the involvement of hippocampus in brain diseases and welcomes both original research articles and review papers that deal with the molecular and cellular mechanisms underlying various cerebral pathologies associated with hippocampal dysfunction.

You may choose our Joint Special Issue in IJMS.

Prof. Dr. Natalia V. Gulyaeva
Guest Editor

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Keywords

hippocampus
pathology
mechanisms
adult hippocampal neurogenesis
mental diseases
neurodegeneration
translational research

Related Special Issue

Molecular and Cellular Mechanisms of Brain Disease: Hippocampus as a Nodal Point in International Journal of Molecular Sciences (16 articles)

Published Papers (4 papers)

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Research

28 pages, 1745 KiB

Open AccessArticle

Cholinergic Internal and Projection Systems of Hippocampus and Neocortex Critical for Early Spatial Memory Consolidation in Normal and Chronic Cerebral Hypoperfusion Conditions in Rats with Different Abilities to Consolidation: The Role of Cholinergic Interneurons of the Hippocampus

by Elena I. Zakharova, Andrey T. Proshin, Mikhail Y. Monakov and Alexander M. Dudchenko

Biomedicines 2022, 10(7), 1532; https://doi.org/10.3390/biomedicines10071532 - 28 Jun 2022

Cited by 1 | Viewed by 1293

Abstract

The role of cholinergic projection systems of the neocortex and hippocampus in memory consolidation in healthy and neuropathological conditions has been subject to intensive research. On the contrary, the significance of cholinergic cortical and hippocampal interneurons in learning has hardly been studied. We aimed to evaluate the role of both cholinergic projection neurons and interneurons of the neocortex and hippocampus at an early stage of spatial memory consolidation (2s1) in normal and chronic brain hypoperfusion conditions. Control rats and rats subjected to permanent two-vessel occlusion were trained with the Morris water maze, and the activity of membrane-bound and water-soluble choline acetyltransferase was evaluated in the sub-fractions of ‘light’ and ‘heavy’ synaptosomes of the neocortex and hippocampus, in which the presynapses of cholinergic projections and interneurons, respectively, are concentrated. Animals were ranked into quartiles according to their performance on stage 2s1. We found: (1) quartile-dependent cholinergic composition of 2s1 function and dynamics of cholinergic synaptic plasticity under cerebral hypoperfusion; (2) cholinergic hippocampal interneurons are necessary for successful 2s1 consolidation; (3) cholinergic neocortical interneurons and projections can be critical for 2s1 consolidation in less learning rats. We conclude that targeted modulation of cholinergic synaptic activity in the hippocampus and neocortex can be effective in reversing the cognitive disturbance of cerebral hypoperfusion. We discuss the possible ways to restore the impaired spatial memory 2s1 in the presence of cerebral hypoperfusion. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Brain Disease: Hippocampus as a Nodal Point)

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14 pages, 1497 KiB

Open AccessArticle

Hippocampal Estrogen Signaling Mediates Sex Differences in Retroactive Interference

by Marco Rinaudo, Francesca Natale, Francesco La Greca, Matteo Spinelli, Antonella Farsetti, Fabiola Paciello, Salvatore Fusco and Claudio Grassi

Biomedicines 2022, 10(6), 1387; https://doi.org/10.3390/biomedicines10061387 - 11 Jun 2022

Cited by 4 | Viewed by 2041

Abstract

Despite being a crucial physiological function of the brain, the mechanisms underlying forgetting are still poorly understood. Estrogens play a critical role in different brain functions, including memory. However, the effects of sex hormones on forgetting vulnerabilitymediated by retroactive interference (RI), a phenomenon in which newly acquired information interferes with the retrieval of already stored information, are still poorly understood. The aim of our study was to characterize the sex differences in interference-mediated forgetting and identify the underlying molecular mechanisms. We found that adult male C57bl/6 mice showed a higher susceptibility to RI-dependent memory loss than females. The preference index (PI) in the NOR paradigm was 52.7 ± 5.9% in males and 62.3 ± 13.0% in females. The resistance to RI in female mice was mediated by estrogen signaling involving estrogen receptor α activation in the dorsal hippocampus. Accordingly, following RI, females showed higher phosphorylation levels (+30%) of extracellular signal-regulated kinase1/2 (ERK1/2) in the hippocampus. Pharmacological inhibition of ERK1/2 made female mice prone to RI. The PI was 70.6 ± 11.0% in vehicle-injected mice and 47.4 ± 10.8% following PD98059 administration. Collectively, our data suggest that hippocampal estrogen α receptor-ERK1/2 signaling is critically involved in a pattern separation mechanism that inhibits object-related RI in female mice. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Brain Disease: Hippocampus as a Nodal Point)

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15 pages, 2049 KiB

Open AccessArticle

Time Course of Neurobehavioral Disruptions and Regional Brain Metabolism Changes in the Rotenone Mice Model of Parkinson’s Disease

by Dmitry Troshev, Dmitry Voronkov, Anastasia Pavlova, Denis Abaimov, Alexander Latanov, Tatiana Fedorova and Daniil Berezhnoy

Biomedicines 2022, 10(2), 466; https://doi.org/10.3390/biomedicines10020466 - 16 Feb 2022

Cited by 1 | Viewed by 2403

Abstract

Parkinson’s disease (PD) is characterized by slow progression with a long prodromal stage and the gradual evolution of both neuropsychological symptoms and subtle motor changes, preceding motor dysfunction. Thus, in order for animal models of PD to be valid, they should reproduce these characteristics of the disease. One of such models, in which neuropathology is induced by chronic injections of low doses of mitochondrial toxin rotenone, is well established in rats. However, data on this model adapted to mice remain controversial. We have designed the study to describe the timecourse of motor and non-motor symptoms during chronic subcutaneous administration of rotenone (4 mg/kg daily for 35 days) in C57BL/6 mice. We characterize the underlying neuropathological processes (dopaminergic neuron degeneration, regional brain metabolism, monoamine neurotransmitter and lipid peroxidation changes) at different timepoints: 1 day, 2 weeks and 5 weeks of daily rotenone exposure. Based on the behavioral data, we can describe three stages of pathology: cognitive changes from week 2 of rotenone exposure, subtle motor changes in week 3–4 and motor dysfunction starting roughly from week 4. Neuropathological changes in this model include a general decrease in COX activity in different areas of the brain (acute effect of rotenone) and a more specific decrease in midbrain (chronic effect), followed by significant neurodegeneration in SNpc but not VTA by the 5th week of rotenone exposure. However, we were unable to find changes in the level of monoamine neurotransmitters neither in the striatum nor in the cortex, nor in the level of lipid peroxidation in the brainstem. Thus, the gradual progression of pathology in this model is linked with metabolic changes, rather than with oxidative stress or tonic neurotransmitter release levels. Overall, this study supports the idea that a low-dose rotenone mouse model can also reproduce different stages of PD as well as rats. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Brain Disease: Hippocampus as a Nodal Point)

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23 pages, 1678 KiB

Open AccessArticle

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

by Galina T. Shishkina, Natalia V. Gulyaeva, Dmitriy A. Lanshakov, Tatyana S. Kalinina, Mikhail V. Onufriev, Yulia V. Moiseeva, Ekaterina V. Sukhareva, Vladimir N. Babenko and Nikolay N. Dygalo

Biomedicines 2021, 9(12), 1840; https://doi.org/10.3390/biomedicines9121840 - 5 Dec 2021

Cited by 6 | Viewed by 2704

Abstract

Acute cerebral ischemia induces distant inflammation in the hippocampus; however, molecular mechanisms of this phenomenon remain obscure. Here, hippocampal gene expression profiles were compared in two experimental paradigms in rats: middle cerebral artery occlusion (MCAO) and intracerebral administration of lipopolysaccharide (LPS). The main finding is that 10 genes (Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1) may represent key molecular links underlying acute activation of immune cells in the hippocampus in response to experimental ischemia. Functional annotation clustering revealed that these genes built the same clusters related to innate immunity/immunity/innate immune response in all MCAO differentially expressed genes and responded to the direct pro-inflammatory stimulus group. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses also indicate that LPS-responding genes were the most abundant among the genes related to “positive regulation of tumor necrosis factor biosynthetic process”, “cell adhesion”, “TNF signaling pathway”, and “phagosome” as compared with non-responding ones. In contrast, positive and negative “regulation of cell proliferation” and “HIF-1 signaling pathway” mostly enriched with genes that did not respond to LPS. These results contribute to understanding genomic mechanisms of the impact of immune/inflammatory activation on expression of hippocampal genes after focal brain ischemia. Full article

(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Brain Disease: Hippocampus as a Nodal Point)

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