Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice

IntroductionMutations in the methyl-CpG-binding protein-2 gene (MECP2), which cause Rett syndrome (RTT), disrupt neuronal activity; however, the impact of the MECP2 loss-of-function on the cytoarchitecture of medial entorhinal cortex layer II (MECII) neurons—crucial for spatial memory and learning—r...

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Main Authors: Manigandan Krishnan, Ayishal B. Mydeen, Mohammed M. Nakhal, Marwa F. Ibrahim, Richard L. Jayaraj, Milos R. Ljubisavljevic, Mohammad I. K. Hamad, Fatima Y. Ismail
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Neuroanatomy
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Online Access:https://www.frontiersin.org/articles/10.3389/fnana.2025.1580435/full
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author Manigandan Krishnan
Ayishal B. Mydeen
Mohammed M. Nakhal
Marwa F. Ibrahim
Richard L. Jayaraj
Milos R. Ljubisavljevic
Mohammad I. K. Hamad
Fatima Y. Ismail
Fatima Y. Ismail
author_facet Manigandan Krishnan
Ayishal B. Mydeen
Mohammed M. Nakhal
Marwa F. Ibrahim
Richard L. Jayaraj
Milos R. Ljubisavljevic
Mohammad I. K. Hamad
Fatima Y. Ismail
Fatima Y. Ismail
author_sort Manigandan Krishnan
collection DOAJ
description IntroductionMutations in the methyl-CpG-binding protein-2 gene (MECP2), which cause Rett syndrome (RTT), disrupt neuronal activity; however, the impact of the MECP2 loss-of-function on the cytoarchitecture of medial entorhinal cortex layer II (MECII) neurons—crucial for spatial memory and learning—remains poorly understood.MethodsIn this study, we utilized Golgi staining and neuron tracing in the Mecp2+/− mouse model of RTT to investigate the pyramidal and stellate cell alterations in MECII.Results and discussionOur findings revealed that pyramidal cells displayed a significant reduction in apical dendritic length, soma size, and spine density, while basal dendrites showed increased dendritic complexity and branching. On the other hand, stellate cells exhibited dendritic hypertrophy along with increased soma size, primary dendrites, and localized increase in dendritic intersections, despite an overall reduction in total dendritic length and spine density. These findings underscore the notion that MECP2 loss-of-function can disrupt MECII pyramidal and stellate cell cytoarchitecture in a cell-type-specific manner, emphasizing its critical role in maintaining proper dendritic morphology in circuits, which is crucial for learning and memory.
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spelling doaj-art-8b7be3d9fa184c0a97d50e6d201010c72025-08-20T03:32:09ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292025-06-011910.3389/fnana.2025.15804351580435Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome miceManigandan Krishnan0Ayishal B. Mydeen1Mohammed M. Nakhal2Marwa F. Ibrahim3Richard L. Jayaraj4Milos R. Ljubisavljevic5Mohammad I. K. Hamad6Fatima Y. Ismail7Fatima Y. Ismail8Department of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Physiology, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Anatomy, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Pediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab EmiratesDepartment of Neurology (Adjunct), Johns Hopkins University School of Medicine, Baltimore, MD, United StatesIntroductionMutations in the methyl-CpG-binding protein-2 gene (MECP2), which cause Rett syndrome (RTT), disrupt neuronal activity; however, the impact of the MECP2 loss-of-function on the cytoarchitecture of medial entorhinal cortex layer II (MECII) neurons—crucial for spatial memory and learning—remains poorly understood.MethodsIn this study, we utilized Golgi staining and neuron tracing in the Mecp2+/− mouse model of RTT to investigate the pyramidal and stellate cell alterations in MECII.Results and discussionOur findings revealed that pyramidal cells displayed a significant reduction in apical dendritic length, soma size, and spine density, while basal dendrites showed increased dendritic complexity and branching. On the other hand, stellate cells exhibited dendritic hypertrophy along with increased soma size, primary dendrites, and localized increase in dendritic intersections, despite an overall reduction in total dendritic length and spine density. These findings underscore the notion that MECP2 loss-of-function can disrupt MECII pyramidal and stellate cell cytoarchitecture in a cell-type-specific manner, emphasizing its critical role in maintaining proper dendritic morphology in circuits, which is crucial for learning and memory.https://www.frontiersin.org/articles/10.3389/fnana.2025.1580435/fullRett syndromeMecp2 mouse modeldendritic branchingpyramidal cellsstellate cellsmedial entorhinal cortex
spellingShingle Manigandan Krishnan
Ayishal B. Mydeen
Mohammed M. Nakhal
Marwa F. Ibrahim
Richard L. Jayaraj
Milos R. Ljubisavljevic
Mohammad I. K. Hamad
Fatima Y. Ismail
Fatima Y. Ismail
Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice
Frontiers in Neuroanatomy
Rett syndrome
Mecp2 mouse model
dendritic branching
pyramidal cells
stellate cells
medial entorhinal cortex
title Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice
title_full Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice
title_fullStr Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice
title_full_unstemmed Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice
title_short Altered dendritic morphology of MEC II pyramidal and stellate cells in Rett syndrome mice
title_sort altered dendritic morphology of mec ii pyramidal and stellate cells in rett syndrome mice
topic Rett syndrome
Mecp2 mouse model
dendritic branching
pyramidal cells
stellate cells
medial entorhinal cortex
url https://www.frontiersin.org/articles/10.3389/fnana.2025.1580435/full
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