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JOURNAL ARTICLE
Carla Liria Sánchez-Lafuente, Laura Martinez-Verbo, Jenessa N Johnston, Jennifer Floyd, Manel Esteller, Lisa E Kalynchuk, Juan Ausió, Hector J Caruncho
Women are disproportionately affected by stress-related disorders like depression. In our prior research, we discovered that females exhibit lower basal hypothalamic reelin levels, and these levels are differentially influenced by chronic stress induced through repeated corticosterone (CORT) injections. Although epigenetic mechanisms involving DNA methylation and the formation of repressor complexes by DNA methyl-transferases (DNMTs) and Methyl-CpG binding protein 2 (MeCP2) have been recognized as regulators of reelin expression in vitro, there is limited understanding of the impact of stress on the epigenetic regulation of reelin in vivo and whether sex differences exist in these mechanisms...
April 12, 2024: Neuroscience Letters
#2
JOURNAL ARTICLE
Laurent Calvier, Anna Alexander, Austin T Marckx, Maria Z Kounnas, Murat Durakoglugil, Joachim Herz
Reelin, a large extracellular glycoprotein, plays critical roles in neuronal development and synaptic plasticity in the central nervous system (CNS). Recent studies have revealed non-neuronal functions of plasma Reelin in inflammation by promoting endothelial-leukocyte adhesion through its canonical pathway in endothelial cells (via ApoER2 acting on NF-κB), as well as in vascular tone regulation and thrombosis. In this study, we have investigated the safety and efficacy of selectively depleting plasma Reelin as a potential therapeutic strategy for chronic inflammatory diseases...
March 27, 2024: Cells
#3
JOURNAL ARTICLE
Kaylene K A Scheil, Carla L Sánchez-Lafuente, Brady S Reive, Ciara S Halvorson, Jennifer Floyd, Hannah M O Reid, Jenessa N Johnston, Lisa E Kalynchuk, Hector J Caruncho
There is an urgent need for novel antidepressants, given that approximately 30% of those diagnosed with depression do not respond adequately to first-line treatment. Additionally, monoaminergic-based antidepressants have a substantial therapeutic time-lag, often taking months to reach full therapeutic effect. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist is the only current effective rapid-acting antidepressant, demonstrating efficacy within hours and lasting up to two weeks with an acute dose...
March 27, 2024: Progress in Neuro-psychopharmacology & Biological Psychiatry
#4
JOURNAL ARTICLE
Erika Ongemach, Daniela Zerrinius, Philipp Heimann, Christian Rainer Wirtz, Klaus-Michael Debatin, Mike-Andrew Westhoff, Aurelia Peraud
Glioblastoma, the most common and lethal primary adult brain tumor, cannot be successfully removed surgically due to its highly invasive nature. Therapeutically, approaches must be aimed at a systemic brain disease and not merely at a tumor located within the brain, unless a successful containment strategy can be found. Reelin, an extracellular matrix glycoprotein, plays an important role in neuronal migration and serves here as a natural stop signal. Interestingly, the expression of reelin is negatively associated with tumor grade and, within glioblastoma, correlates with increased overall survival...
March 21, 2024: Pharmaceuticals
#5
JOURNAL ARTICLE
B S Reive, J Johnston, C L Sánchez-Lafuente, Kaylene Scheil, K Kurz, L E Kalynchuk, H J Caruncho
Novel antidepressants are predominantly evaluated preclinically in rodent models of chronic stress in which animals experience a single prolonged exposure to chronic stress prior to treatment. Rodent models of a single episode of chronic stress translate poorly to human depressive disorders, which are commonly marked by recurring depressive episodes. Intravenous administration of Reelin has previously been shown to resolve immobility in the forced swim test of rats exposed to a single prolonged exposure to chronic stress...
2024: Frontiers in Pharmacology
#6
JOURNAL ARTICLE
Jiangyan Zhang, Rui Zhao, Shiying Lin, Dong Yang, Shan Lu, Zenan Liu, Yuanyuan Gao, Yiyun Zhang, Bing Hou, Chao Xi, Jin Liu, Jie Bing, Erli Pang, Kui Lin, Shaoju Zeng
The mechanisms underlying the organization and evolution of the telencephalic pallium are not yet clear.. To address this issue, we first performed comparative analysis of genes critical for the development of the pallium (Emx1/2 and Pax6) and subpallium (Dlx2 and Nkx1/2) among 500 vertebrate species. We found that these genes have no obvious variations in chromosomal duplication/loss, gene locus synteny or Darwinian selection. However, there is an additional fragment of approximately 20 amino acids in mammalian Emx1 and a poly-(Ala)6-7 in Emx2...
March 13, 2024: Scientific Reports
#7
JOURNAL ARTICLE
Hee Ra Park, Mudan Cai
Lilii Bulbus (Lilium lancifolium Thunberg) has a proneurogenic effect on the hippocampus. However, its effects on epilepsy and associated pathological features remain unknown. In this study, we investigated the antiseizure effects of a water extract of Lilii Bulbus (WELB) in mouse model of pentylenetetrazol (PTZ)-induced seizure. Mice were injected with PTZ once every 48 h until full kindling was achieved. WELB (100 and 500 mg/kg) was orally administered once daily before PTZ administration and during the kindling process...
March 8, 2024: Biomedicine & Pharmacotherapy
#8
JOURNAL ARTICLE
Nieves Mingo-Moreno, Pavel Truschow, Jochen F Staiger, Robin J Wagener
In mammalian neocortex development, every cohort of newborn neurons is guided toward the marginal zone, leading to an "inside-out" organization of the 6 neocortical layers. This migratory pattern is regulated by the extracellular glycoprotein Reelin. The reeler mouse shows a homozygous mutation of the reelin gene. Using RNA in situ hybridization we could demonstrate that the Reelin-deficient mouse cortex (male and female) displays an increasing lamination defect along the rostro-caudal axis that is characterized by strong cellular intermingling, but roughly reproduces the "inside-out" pattern in rostral cortex, while caudal cortex shows a relative inversion of neuronal positioning ("outside-in")...
January 31, 2024: Cerebral Cortex
#9
JOURNAL ARTICLE
Attila Ozsvár, Meike Claudia Sieburg, Monica Dahlstrup Sietam, Wen-Hsien Hou, Marco Capogna
The mouse basolateral amygdala (BLA) contains various GABAergic interneuron subpopulations, which have distinctive roles in the neuronal microcircuit controlling numerous behavioral functions. In mice, roughly 15% of the BLA GABAergic interneurons express neuropeptide Y (NPY), a reasonably characteristic marker for neurogliaform cells (NGFCs) in cortical-like brain structures. However, genetically labeled putative NPY-expressing interneurons in the BLA yield a mixture of interneuron subtypes besides NGFCs. Thus, selective molecular markers are lacking for genetically accessing NGFCs in the BLA...
2024: Frontiers in Cellular Neuroscience
#10
JOURNAL ARTICLE
Ryota Ojiro, Shunsuke Ozawa, Xinyu Zou, Qian Tang, Gye-Hyeong Woo, Makoto Shibutani
Studies on the effects of glyphosate (GlyP) and glyphosate-based herbicides (GBHs) on cerebellar development are extremely limited. This study examined the effects of maternal exposure to GlyP and GBH on rat cerebellar development in male offspring. From day 6 of gestation until day 21 postpartum at weaning, dams were given GlyP at 1.5% or 3.0% in diet or GBH at 1.0% in drinking water (corresponding to 0.36% GlyP). At weaning, GBH exposure was linked to increased numbers of DCX+ migrating granule cells in the cortex and TUNEL+ apoptotic cells in the internal granular layer (IGL), suggesting the disappearance of mismigrated granule cells via apoptosis...
February 5, 2024: Environmental Toxicology
#11
JOURNAL ARTICLE
Mario O Caracci, Héctor Pizarro, Carlos Alarcón-Godoy, Luz M Fuentealba, Pamela Farfán, Raffaella De Pace, Natacha Santibañez, Viviana A Cavieres, Tammy P Pástor, Juan S Bonifacino, Gonzalo A Mardones, María-Paz Marzolo
Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes export of selected cargo proteins from the trans-Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4...
January 26, 2024: Progress in Neurobiology
#12
Gavin D Lagani, Weiwei Lin, Sahana Natarajan, Noah Lampl, Evelyn R Harper, Andrew Emili, Uwe Beffert, Angela Ho
UNLABELLED: Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with non-canonical receptors and unidentified co-receptors; however, the effects of which are less understood. Using high-throughput tandem mass tag LC-MS/MS-based proteomics and gene set enrichment analysis, we identified both shared and unique intracellular pathways activated by Reelin through its canonical and non-canonical signaling in primary murine neurons during dendritic growth and arborization...
January 12, 2024: bioRxiv
#13
REVIEW
Ciara S Halvorson, Carla Liria Sánchez-Lafuente, Jenessa N Johnston, Lisa E Kalynchuk, Hector J Caruncho
Current pharmacological treatments for depression fail to produce adequate remission in a significant proportion of patients. Increasingly, other systems, such as the microbiome-gut-brain axis, are being looked at as putative novel avenues for depression treatment. Dysbiosis and dysregulation along this axis are highly comorbid with the severity of depression symptoms. The endogenous extracellular matrix protein reelin is present in all intestinal layers as well as in myenteric and submucosal ganglia, and its receptors are also present in the gut...
January 9, 2024: International Journal of Molecular Sciences
#14
JOURNAL ARTICLE
Swamynathan Sowndharya, Koilmani Emmanuvel Rajan
Environmental enrichment (EE) through combination of social and non-biological stimuli enhances activity-dependent synaptic plasticity and improves behavioural performance. Our earlier studies have suggested that EE resilience the stress induced depression/ anxiety-like behaviour in Indian field mice Mus booduga. This study was designed to test whether EE reverses the social isolation (SI) induced effect and improve memory. Field-caught mice M. booduga were subjected to behaviour test (Direct wild, DW), remaining animals were housed under SI for ten days and then housed for short-term at standard condition (STSC)/ long-term at standard condition (LTSC) or as group in EE cage...
2024: PloS One
#15
Mario O Caracci, Héctor Pizarro, Carlos Alarcón-Godoy, Luz M Fuentealba, Pamela Farfán, Raffaella De Pace, Natacha Santibañez, Viviana A Cavieres, Tammy P Pástor, Juan S Bonifacino, Gonzalo A Mardones, María-Paz Marzolo
Adaptor protein complex 4 (AP-4) is a heterotetrameric complex that promotes protein export from the trans -Golgi network. Mutations in each of the AP-4 subunits cause a complicated form of Hereditary Spastic Paraplegia (HSP). Herein, we report that ApoER2, a receptor in the Reelin signaling pathway, is a cargo of the AP-4 complex. We identify the motif ISSF/Y within the ApoER2 cytosolic domain as necessary for interaction with the canonical signal-binding pocket of the µ4 (AP4M1) subunit of AP-4. AP4E1 -knock-out (KO) HeLa cells and hippocampal neurons from Ap4e1 -KO mice display increased Golgi localization of ApoER2...
December 22, 2023: bioRxiv
#16
Patricia E Phelps, Sung Min Ha, Rana R Khankan, Mahlet A Mekonnen, Giovanni Juarez, Kaitlin L Ingraham Dixie, Yen-Wei Chen, Xia Yang
Olfactory ensheathing cells (OECs) are unique glial cells found in both the central and peripheral nervous systems where they support the continuous axonal outgrowth of immature olfactory sensory neurons to their targets. Here we show that following severe spinal cord injury, olfactory bulb-derived OECs transplanted near the injury site modify the normally inhibitory glial scar and facilitate axon regeneration past the scar border and into the lesion center. To understand the mechanisms underlying the reparative properties of such transplanted OECs, we used single-cell RNA-sequencing to study their gene expression programs...
December 21, 2023: bioRxiv
#17
REVIEW
Mohammad I K Hamad, Bright Starling Emerald, Kukkala K Kumar, Marwa F Ibrahim, Bassam R Ali, Mo'ath F Bataineh
Proper growth and branching of dendrites are crucial for adequate central nervous system (CNS) functioning. The neuronal dendritic geometry determines the mode and quality of information processing. Any defects in dendrite development will disrupt neuronal circuit formation, affecting brain function. Besides cell-intrinsic programmes, extrinsic factors regulate various aspects of dendritic development. Among these extrinsic factors are extracellular molecular signals which can shape the dendrite architecture during early development...
2023: Frontiers in Cell and Developmental Biology
#18
JOURNAL ARTICLE
Lijuan Pei, Zhaohui Ouyang, Hongjie Zhang, Shiqi Huang, Rui Jiang, Bilin Liu, Yansong Tang, Mengying Feng, Min Yuan, Haocun Wang, Su Yao, Shuyue Shi, Zhao Yu, Dachun Xu, Guohua Gong, Ke Wei
Adult mammalian cardiomyocytes have minimal cell cycle capacity, which leads to poor regeneration after cardiac injury such as myocardial infarction. Many positive regulators of cardiomyocyte cell cycle and cardioprotective signals have been identified, but extracellular signals that suppress cardiomyocyte proliferation are poorly understood. We profiled receptors enriched in postnatal cardiomyocytes, and found that very-low-density-lipoprotein receptor (Vldlr) inhibits neonatal cardiomyocyte cell cycle. Paradoxically, Reelin, the well-known Vldlr ligand, expressed in cardiac Schwann cells and lymphatic endothelial cells, promotes neonatal cardiomyocyte proliferation...
December 26, 2023: Basic Research in Cardiology
#19
REVIEW
Renata Markiewicz, Agnieszka Markiewicz-Gospodarek, Bartosz Borowski, Mateusz Trubalski, Bartosz Łoza
Recent research emphasizes the significance of studying the quality of life of schizophrenia patients, considering the complex nature of the illness. Identifying neuronal markers for early diagnosis and treatment is crucial. Reelin (RELN) stands out among these markers, with genetic studies highlighting its role in mental health. Suppression of RELN expression may contribute to cognitive deficits by limiting dendritic proliferation, affecting neurogenesis, and leading to improper neuronal circuits. Although the physiological function of reelin is not fully understood, it plays a vital role in hippocampal cell stratification and neuroglia formation...
December 11, 2023: Brain Sciences
#20
JOURNAL ARTICLE
Junhao Wen, Ilya M Nasrallah, Ahmed Abdulkadir, Theodore D Satterthwaite, Zhijian Yang, Guray Erus, Timothy Robert-Fitzgerald, Ashish Singh, Aristeidis Sotiras, Aleix Boquet-Pujadas, Elizabeth Mamourian, Jimit Doshi, Yuhan Cui, Dhivya Srinivasan, Ioanna Skampardoni, Jiong Chen, Gyujoon Hwang, Mark Bergman, Jingxuan Bao, Yogasudha Veturi, Zhen Zhou, Shu Yang, Paola Dazzan, Rene S Kahn, Hugo G Schnack, Marcus V Zanetti, Eva Meisenzahl, Geraldo F Busatto, Benedicto Crespo-Facorro, Christos Pantelis, Stephen J Wood, Chuanjun Zhuo, Russell T Shinohara, Ruben C Gur, Raquel E Gur, Nikolaos Koutsouleris, Daniel H Wolf, Andrew J Saykin, Marylyn D Ritchie, Li Shen, Paul M Thompson, Olivier Colliot, Katharina Wittfeld, Hans J Grabe, Duygu Tosun, Murat Bilgel, Yang An, Daniel S Marcus, Pamela LaMontagne, Susan R Heckbert, Thomas R Austin, Lenore J Launer, Mark Espeland, Colin L Masters, Paul Maruff, Jurgen Fripp, Sterling C Johnson, John C Morris, Marilyn S Albert, R Nick Bryan, Susan M Resnick, Yong Fan, Mohamad Habes, David Wolk, Haochang Shou, Christos Davatzikos
Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated...
December 26, 2023: Proceedings of the National Academy of Sciences of the United States of America
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