Reelin Signaling and Synaptic Plasticity in Schizophrenia

Markiewicz, Renata; Markiewicz-Gospodarek, Agnieszka; Borowski, Bartosz; Trubalski, Mateusz; Łoza, Bartosz

doi:10.3390/brainsci13121704

Cited by 3 publications

(1 citation statement)

References 117 publications

(264 reference statements)

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“…Purkinje cell arrangement from the cluster stage is determined by Reelin gene expression and its downstream molecules, apolipoprotein E receptor 2 (ApoER2) and very-low-density lipoprotein receptor (VLDRL) (Markiewicz et al, 2023;Nimura et al, 2019;Rahimi-Balaei et al, 2018). Mutations in the Reelin gene and targeted deletion of ApoER2 and VLDRL genes cause ectopic Purkinje cells by preventing cluster dispersal (Jossin, 2020;Nimura et al, 2019;Rahimi-Balaei et al, 2018;Sotelo and Rossi, 2021).…”

Section: Purkinje Cell Layermentioning

confidence: 99%

Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats

Mwachaka,

Gichangi,

Abdelmalek

et al. 2024

Intl J of Devlp Neuroscience

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The cerebellum has a long, protracted developmental period that spans from the embryonic to postnatal periods; as a result, it is more sensitive to intrauterine and postnatal insults like nutritional deficiencies. Folate is crucial for foetal and early postnatal brain development; however, its effects on cerebellar growth and development are unknown. The aim of this study was to examine the effects of maternal folate intake on the histomorphology and cell density of the developing cerebellum. Twelve adult female rats (rattus norvegicus) were randomly assigned to one of four premixed diet groups: standard (2 mg/kg), folate‐deficient (0 mg/kg), folate‐supplemented (8 mg/kg) or folate supra‐supplemented (40 mg/kg). The rats started their diets 14 days before mating and consumed them throughout pregnancy and lactation. On postnatal days 1, 7, 21 and 35, five pups from each group were sacrificed, and their brains were processed for light microscopic analysis. Histomorphology and cell density of the external granule, molecular, Purkinje and internal granule layers were obtained. The folate‐deficient diet group had smaller, dysmorphic cells and significantly lower densities of external granule, molecular, Purkinje and internal granule cells. Although the folate‐enriched groups had greater cell densities than the controls, the folate‐supplemented group had considerably higher cell densities than the supra‐supplemented group. The folate supra‐supplemented group had ectopic Purkinje cells in the internal granule cell layer. These findings imply that a folate‐deficient diet impairs cellular growth and reduces cell density in the cerebellar cortex. On the other hand, folate supplementation increases cell densities, but there appears to be an optimal dose of supplementation since excessive folate levels may be detrimental.

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Section: Purkinje Cell Layermentioning

confidence: 99%

Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats

Mwachaka,

Gichangi,

Abdelmalek

et al. 2024

Intl J of Devlp Neuroscience

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OCRL1 Deficiency Affects the Intracellular Traffic of ApoER2 and Impairs Reelin-Induced Responses

Fuentealba,

Pizarro,

Marzolo

2024

Biomolecules

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Lowe Syndrome (LS) is a rare X-linked disorder characterized by renal dysfunction, cataracts, and several central nervous system (CNS) anomalies. The mechanisms underlying the neurological dysfunction in LS remain unclear, albeit they share some phenotypic characteristics similar to the deficiency or dysfunction of the Reelin signaling, a relevant pathway with roles in CNS development and neuronal functions. In this study, we investigated the role of OCRL1, an inositol polyphosphate 5-phosphatase encoded by the OCRL gene, mutated in LS, focusing on its impact on endosomal trafficking and receptor recycling in human neuronal cells. Specifically, we tested the effects of OCRL1 deficiency in the trafficking and signaling of ApoER2/LRP8, a receptor for the ligand Reelin. We found that loss of OCRL1 impairs ApoER2 intracellular trafficking, leading to reduced receptor expression and decreased levels at the plasma membrane. Additionally, human neurons deficient in OCRL1 showed impairments in ApoER2/Reelin-induced responses. Our findings highlight the critical role of OCRL1 in regulating ApoER2 endosomal recycling and its impact on the ApoER2/Reelin signaling pathway, providing insights into potential mechanisms underlying the neurological manifestations of LS.

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Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia

Markiewicz,

Markiewicz-Gospodarek,

Trubalski

et al. 2024

JCM

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Introduction: Reelin is a neuropeptide responsible for the migration and positioning of pyramidal neurons, interneurons, and Purkinje cells. In adulthood, it still supports neuroplasticity, especially dendritic spines formation and glutamatergic neurotransmission. Genetic studies have confirmed the involvement of reelin system failure in the etiopathogenesis of mental diseases, including schizophrenia. Given the role of reelin in brain cytoarchitectonics and the regularly observed reduction in its activity in prefrontal areas in cases of schizophrenia, dysfunction of the reelin pathway fits the neurodevelopmental hypothesis of schizophrenia, both as a biochemical predisposition and/or the ultimate trigger of psychosis and as a biosocial factor determining the clinical course, and finally, as a potential target for disease monitoring and treatment. Aim: The purpose of this study was to examine associations of the reelin blood level with clinical and neurocognitive parameters during an intensive, structured neurofeedback therapy of patients with schizophrenia. Methods: Thirty-seven male patients with paranoid schizophrenia were randomly divided into two groups: a group with 3-month neurofeedback as an add-on to ongoing antipsychotic treatment (NF, N18), and a control group with standard social support and antipsychotic treatment (CON, N19). The reelin serum concentration, clinical and neurocognitive tests were compared between the groups. Results: After 3-month trial (T2), the reelin serum level increased in the NF group vs. the CON group. The negative and general symptoms of PANSS (Positive and Negative Syndrome Scale) were reduced significantly more in the NF group at T2, and the d2 (d2 Sustained Attention Test) and BCIS (Beck Cognitive Insight Scale) scores improved only in the NF group. The AIS scores improved more dynamically in the NF group, but not enough to differentiate them from the CON group at T2. Conclusions: The clinical and neurocognitive improvement within the 3-month NF add-on therapy trial was associated with a significant increase of reelin serum level in schizophrenia patients.

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Reelin Signaling and Synaptic Plasticity in Schizophrenia

Cited by 3 publications

References 117 publications

Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats

Impact of varying maternal dietary folate intake on cerebellar cortex histomorphology and cell density in offspring rats

OCRL1 Deficiency Affects the Intracellular Traffic of ApoER2 and Impairs Reelin-Induced Responses

Neurocognitive, Clinical and Reelin Activity in Rehabilitation Using Neurofeedback Therapy in Patients with Schizophrenia

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