Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis

Sitaš, Barbara; Bobić-Rasonja, Mihaela; Mrak, Goran; Trnski, Sara; Skorić, Magdalena Krbot; Orešković, Darko; Knezović, Vinka; Gadže, Željka Petelin; Petanjek, Zdravko; Šimić, Goran; Kolenc, Danijela; Jovanov-Milošević, Nataša

doi:10.3390/ijms23158197

Cited by 6 publications

(11 citation statements)

References 38 publications

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“…Unfortunately, all of the children used in this study received various pharmacological treatments according to their medical conditions, since many of them were treated in the intensive care unit before death. The influence of medical drugs and pathological conditions (e.g., epilepsy) on PV immunoreactivity has already been demonstrated (Wittner et al, 2001;Ábrahám et al, 2020;Sitaš et al, 2022), however, one can propose that PV expression was affected similarly in children used in our present study, due to their severe illnesses. The only exception is one of the 5-month old babies who potentially had no previous medication and deceased due to sudden infant death syndrome (SIDS).…”

Section: Technical Consideration and Limitations Of The Studymentioning

confidence: 52%

Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation

Ábrahám

Kojima²,

Götzer³

et al. 2023

Front. Neuroanat.

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Introduction: Parvalbumin (PV) is a calcium-binding protein present in fast-spiking GABAergic neurons, such as basket and axo-axonic cells. Previous studies in non-human primates reported prenatal expression of PV in the temporal archicortex including entorhinal cortex and hippocampal formation. In contrast, PV-immunoreactivity was observed only postnatally in the human entorhinal cortex. Regarding PV expression in the human hippocampal formation, no information is available.Methods: In this study, the neurochemical maturation of PV-immunoreactive interneurons was studied in the postnatal developing human hippocampal formation.Results: Before birth, no PV-immunoreactive neurons could be detected in the human hippocampus. At birth, only a few PV-immunoreactive neurons were visible in Ammon’s horn. The first PV-immunoreactive cells in the hilus of the dentate gyrus appeared at the age of 1 month. Even at the age of 5 months, only a few PV-immunopositive cells were present in the dentate hilus. The number of cells and their dendritic and axonal arborization in Ammon’s horn and in the dentate gyrus gradually increased with age. Even at the age of 2 years, dendritic tree and axons of PV-immunoreactive neurons were less complex than can be seen in 8 and 11 years old children.Discussion: Our results showed that long-lasting maturation of PV-immunoreactive interneurons follows the developmental sequence of the subfields of the human hippocampal formation and provides further morphological evidence for the long-lasting functional maturation of the human cortex.

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Section: Technical Consideration and Limitations Of The Studymentioning

confidence: 52%

Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation

Ábrahám

Kojima²,

Götzer³

et al. 2023

Front. Neuroanat.

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“…Chondroitin sulfate proteoglycans, particularly members of the lectican family including versican, neurocan, brevican and aggrecan, are major components of the PNN, 40 and immunohistochemical staining techniques have been used in many publications to visualize aggrecan, [5][6][7][8][9][10][11][12][13][14][15] or lecticans. [5][6][7][8][10][11][12][15][16][17][18][19][20][21][22][23][24][25]27,28,41 It has to be noted, however, that it is difficult to immunohistochemically differentiate the very similar molecular structure of these glycosaminoglycan molecules adhering to the plasma membrane of neurons, which may also include keratan sulfate, 8,42,43 Several studies addressed PNN in the epileptic disease condition. The published results were, however, not unequivocal as outlined below.…”

Section: Discussionmentioning

confidence: 99%

“…4). Herein, we used immunohistochemical staining for aggrecan as a biomarker for PNN as has been repetitively shown in previous publications 5–15 . PNN are found mostly around neurophysiologically highly active interneurons containing Parvalbumin (PV), 16–18 but also occur around excitatory neurons 6–8,19 .…”

Section: Introductionmentioning

confidence: 99%

Age‐dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy

Lehner,

Hoffmann,

Rampp

et al. 2024

Epilepsia Open

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ObjectivePerineuronal nets (PNN) are specialized extracellular matrix (ECM) components of the central nervous system, frequently accumulating at the surface of inhibitory GABAergic interneurons. While an altered distribution of PNN has been observed in neurological disorders including Alzheimer's disease, schizophrenia and epilepsy, their anatomical distribution also changes during physiological brain maturation and aging. Such an age‐dependent shift was experimentally associated also with hippocampal engram formation during brain maturation. Our aim was to histopathologically assess PNN in the hippocampus of adult and pediatric patients with temporal lobe epilepsy (TLE) compared to age‐matched post‐mortem control subjects and to compare PNN‐related changes with memory impairment observed in our patient cohort.MethodsSixty‐six formalin‐fixed and paraffin‐embedded tissue specimens of the human hippocampus were retrieved from the European Epilepsy Brain Bank. Twenty‐nine patients had histopathologically confirmed hippocampal sclerosis (HS), and eleven patients suffered from TLE without HS. PNN were immunohistochemically visualized using an antibody directed against aggrecan and manually counted from hippocampus subfields and the subiculum.ResultsPNN density increased with age in both human controls and TLE patients. However, their density was significantly higher in all HS patients compared to age‐matched controls. Intriguingly, TLE patients presented presurgically with better memory when their hippocampal PNN density was higher (p < 0.05).SignificanceOur results were compatible with age‐dependent ECM specialization in the human hippocampus and its precocious aging in the epileptic condition. These observations confirm recent experimental animal models and also support the notion that PNN play a role in memory formation in the human brain.Plain Language Summary“Perineuronal nets” (PNN) are a specialized compartment of the extracellular matrix (ECM), especially surrounding highly active neurons of the mammalian brain. There is evidence that PNN play a role in memory formation, brain maturation, and in some pathologies like Alzheimer's disease, schizophrenia or epilepsy. In this study, we investigated the role of PNN in patients suffering from drug‐resistant focal epilepsy compared to controls. We found that with increasing age, more neurons are surrounded by PNN. Similarly, all epilepsy patients but especially patients with better memory performance also had more PNN. This study raises further interest in studying ECM molecules in the human brain under physiological and pathophysiological conditions.

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“…A recent study demonstrated a reduction in PNNs and significantly altered expression patterns of versican, neurocan, aggrecan, and WFA-specific glycosylation in the hippocampus of patients with drug-resistant mesial temporal lobe epilepsy (MTLE) [ 46 ].…”

Section: Regulation Of Ecm Gene Expression In Development and Diseasementioning

confidence: 99%

Extracellular Matrix Regulation in Physiology and in Brain Disease

Soles

Selimovic

Sbrocco

et al. 2023

IJMS

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The extracellular matrix (ECM) surrounds cells in the brain, providing structural and functional support. Emerging studies demonstrate that the ECM plays important roles during development, in the healthy adult brain, and in brain diseases. The aim of this review is to briefly discuss the physiological roles of the ECM and its contribution to the pathogenesis of brain disease, highlighting the gene expression changes, transcriptional factors involved, and a role for microglia in ECM regulation. Much of the research conducted thus far on disease states has focused on “omic” approaches that reveal differences in gene expression related to the ECM. Here, we review recent findings on alterations in the expression of ECM-associated genes in seizure, neuropathic pain, cerebellar ataxia, and age-related neurodegenerative disorders. Next, we discuss evidence implicating the transcription factor hypoxia-inducible factor 1 (HIF-1) in regulating the expression of ECM genes. HIF-1 is induced in response to hypoxia, and also targets genes involved in ECM remodeling, suggesting that hypoxia could contribute to ECM remodeling in disease conditions. We conclude by discussing the role microglia play in the regulation of the perineuronal nets (PNNs), a specialized form of ECM in the central nervous system. We show evidence that microglia can modulate PNNs in healthy and diseased brain states. Altogether, these findings suggest that ECM regulation is altered in brain disease, and highlight the role of HIF-1 and microglia in ECM remodeling.

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Reorganization of the Brain Extracellular Matrix in Hippocampal Sclerosis

Cited by 6 publications

References 38 publications

Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation

Development of parvalbumin-immunoreactive neurons in the postnatal human hippocampal formation

Age‐dependent increase of perineuronal nets in the human hippocampus and precocious aging in epilepsy

Extracellular Matrix Regulation in Physiology and in Brain Disease

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