scholarly journals Acute MPTP Treatment Impairs Dendritic Spine Density in the Mouse Hippocampus

2021 ◽  
Vol 11 (7) ◽  
pp. 833
Author(s):  
Poornima D. E. Weerasinghe-Mudiyanselage ◽  
Mary Jasmin Ang ◽  
Mai Wada ◽  
Sung-Ho Kim ◽  
Taekyun Shin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons ◽  
Late Phase ◽  
Spine Density ◽  
Branch Points ◽  
Synaptic Structure ◽  
Mouse Hippocampus ◽  
Cornu Ammonis ◽  
Mptp Treatment ◽  
Dendritic Complexity

Among the animal models of Parkinson’s disease (PD), the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model has shown both dopaminergic (DA) damage and related motor control defects, as observed in patients with PD. Recent studies have suggested that the DA system interacts with the synaptic plasticity of the hippocampus in PD. However, little is known about how alterations in the hippocampal structural plasticity are affected by the DA damage in MPTP-lesioned models. In the present study, we investigated alterations in dendritic complexity and spine density in the mouse hippocampus following acute MPTP treatment (22 mg/kg, intraperitoneally, four times/day, 2-h intervals). We confirmed that acute MPTP treatment significantly decreased initial motor function and persistently reduced the number of tyrosine hydroxylase-positive DA neurons in the substantia nigra. Golgi staining showed that acute MPTP treatment significantly reduced the spine density of neuronal dendrites in the cornu ammonis 1 (CA1) apical/basal and dentate gyrus (DG) subregions of the mouse hippocampus at 8 and 16 days after treatment, although it did not affect dendritic complexity (e.g., number of crossing dendrites, total dendritic length, and branch points per neuron) in both CA1 and DG subregions at all time points after treatment. Therefore, the present study provides anatomical evidence that acute MPTP treatment affects synaptic structure in the hippocampus during the late phase after acute MPTP treatment in mice, independent of any changes in the dendritic arborization of hippocampal neurons. These findings offer data for the ability of the acute MPTP-lesioned mouse model to replicate the non-nigrostriatal lesions of clinical PD.

scholarly journals STEP inhibition prevents Aβ-mediated damage in dendritic complexity and spine density in Alzheimer’s disease.

2020 ◽  
Author(s):  
Manavi Chatterjee ◽  
Jeemin Kwon ◽  
Jessie Benedict ◽  
Marija Kamceva ◽  
Pradeep Kurup ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mouse Model ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Spine Density ◽  
Protein Tyrosine ◽  
Dendritic Complexity ◽  
Ad Mouse Model

AbstractLoss of dendritic spines and decline of cognitive function are hallmarks of patients with Alzheimer’s disease (AD). Previous studies have shown that AD pathophysiology involves increased expression of a central nervous system-enriched protein tyrosine phosphatase called STEP (STriatal-Enriched protein tyrosine Phosphatase). STEP opposes the development of synaptic strengthening by dephosphorylating substrates, including GluN2B, Pyk2 and ERK1/2. Genetic reduction of STEP as well as pharmacological inhibition of STEP improves cognitive function and hippocampal memory in the 3xTg AD mouse model. Here, we show that the improved cognitive function is accompanied by an increase in synaptic connectivity in cell cultures as well as in the triple transgenic AD mouse model, further highlighting the potential of STEP inhibitors as a therapeutic agent.

scholarly journals SREBP-1c Deficiency Affects Hippocampal Micromorphometry and Hippocampus-Dependent Memory Ability in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 6103
Author(s):  
Mary Jasmin Ang ◽  
Sueun Lee ◽  
Mai Wada ◽  
Poornima D. E. Weerasinghe-Mudiyanselage ◽  
Sung-Ho Kim ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Regulatory Element ◽  
Memory Function ◽  
Critical Role ◽  
Spine Density ◽  
Branch Points ◽  
Behavioral Alterations ◽  
Underlying Mechanisms ◽  
Functional Neuroplasticity ◽  
Hippocampus Dependent Memory

Changes in structural and functional neuroplasticity have been implicated in various neurological disorders. Sterol regulatory element-binding protein (SREBP)-1c is a critical regulatory molecule of lipid homeostasis in the brain. Recently, our findings have shown the potential involvement of SREBP-1c deficiency in the alteration of novel modulatory molecules in the hippocampus and occurrence of schizophrenia-like behaviors in mice. However, the possible underlying mechanisms, related to neuronal plasticity in the hippocampus, are yet to be elucidated. In this study, we investigated the hippocampus-dependent memory function and neuronal architecture of hippocampal neurons in SREBP-1c knockout (KO) mice. During the passive avoidance test, SREBP-1c KO mice showed memory impairment. Based on Golgi staining, the dendritic complexity, length, and branch points were significantly decreased in the apical cornu ammonis (CA) 1, CA3, and dentate gyrus (DG) subregions of the hippocampi of SREBP-1c KO mice, compared with those of wild-type (WT) mice. Additionally, significant decreases in the dendritic diameters were detected in the CA3 and DG subregions, and spine density was also significantly decreased in the apical CA3 subregion of the hippocampi of KO mice, compared with that of WT mice. Alterations in the proportions of stubby and thin-shaped dendritic spines were observed in the apical subcompartments of CA1 and CA3 in the hippocampi of KO mice. Furthermore, the corresponding differential decreases in the levels of SREBP-1 expression in the hippocampal subregions (particularly, a significant decrease in the level in the CA3) were detected by immunofluorescence. This study suggests that the contributions of SREBP-1c to the structural plasticity of the mouse hippocampus may have underlain the behavioral alterations. These findings offer insights into the critical role of SREBP-1c in hippocampal functioning in mice.

56Fe Irradiation Alters Spine Density and Dendritic Complexity in the Mouse Hippocampus

2015 ◽  
Vol 184 (6) ◽  
pp. 586-594 ◽  
Author(s):  
Antiño R. Allen ◽  
Jacob Raber ◽  
Ayanabha Chakraborti ◽  
Sourabh Sharma ◽  
John R. Fike
Keyword(s):  
Spine Density ◽  
Mouse Hippocampus ◽  
Dendritic Complexity

scholarly journals Enhanced Activity of Alzheimer Disease-associated Variant of Protein Kinase Cα Drives Cognitive Decline

2021 ◽  
Author(s):  
Gema Lorden ◽  
Jacob Wozniak ◽  
Kim Doré ◽  
Lara Dozier ◽  
Chelsea Cates-Gatto ◽  
...  
Keyword(s):  
Catalytic Activity ◽  
Protein Kinase ◽  
Mouse Model ◽  
Cognitive Decline ◽  
Hippocampal Neurons ◽  
Amyloid Β ◽  
Spine Density ◽  
Loss Of Function ◽  
Enhanced Activity ◽  
Behavioral Studies

Abstract Exquisitely tuned activity of protein kinase C (PKC) isozymes is essential to maintaining cellular homeostasis. Whereas loss-of-function mutations are generally associated with cancer, gain-of-function variants in one isozyme, PKCα, are associated with Alzheimer’s disease (AD). Here we show that the enhanced activity of one variant, PKCα M489V, is sufficient to rewire the brain phosphoproteome, drive synaptic degeneration, and impair cognition in a mouse model. This variant causes a modest 30% increase in catalytic activity without altering on/off activation dynamics or stability, underscoring that enhanced catalytic activity is sufficient to drive the biochemical, cellular, and ultimately cognitive effects observed. Analysis of hippocampal neurons from the PKCα M489V mice reveals enhanced amyloid-β-induced synaptic depression and reduced spine density compared to wild-type mice. Behavioral studies reveal that this mutation alone is sufficient to impair cognition, and, when coupled to a mouse model of AD, further accelerates cognitive decline. The druggability of protein kinases positions PKCα as a new and promising therapeutic target in AD.

Abnormal responses of hippocampal neurons to auditory paired-click stimuli in a neurodevelopmental mouse-model of schizophrena

2010 ◽  
Vol 68 ◽  
pp. e201
Author(s):  
Masahiro Okamoto ◽  
Eiichi Jodo ◽  
Tadahiro Katayama ◽  
Yoshiaki Suzuki ◽  
Ken-Yo Hoshino ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hippocampal Neurons

Comparison between 2-day and 10-day MPTP treatment modalities in the mouse model of Parkinson's disease

2003 ◽  
Vol 32 (1) ◽  
pp. 21-28
Author(s):  
Kisok Kim ◽  
Chang Ok Kim ◽  
Youngbuhm Huh ◽  
Byeongwoo Ahn ◽  
Beom Seok Han ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Treatment Modalities ◽  
Mptp Treatment

Ts65Dn, a Mouse Model of Down Syndrome, Exhibits Increased GABAB-Induced Potassium Current

2007 ◽  
Vol 97 (1) ◽  
pp. 892-900 ◽  
Author(s):  
Tyler K. Best ◽  
Richard J. Siarey ◽  
Zygmunt Galdzicki
Keyword(s):  
Down Syndrome ◽  
Mouse Model ◽  
Hippocampal Neurons ◽  
Single Channel ◽  
Extra Chromosome ◽  
Functional Expression ◽  
Chromosome 21 ◽  
Fluctuation Analysis ◽  
Response Curves ◽  
Girk Channel

Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase (∼2-fold) in GABAB-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABAB receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.

scholarly journals Astrocyte-Derived Small Extracellular Vesicles Regulate Dendritic Complexity through miR-26a-5p Activity

2020 ◽  
Author(s):  
Alejandro Luarte ◽  
Roberto Henzi ◽  
Anllely Fernández ◽  
Diego Gaete ◽  
Pablo Cisternas ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Hippocampal Neurons ◽  
Morphological Changes ◽  
Morphological Differentiation ◽  
Total Content ◽  
Neuronal Morphology ◽  
Cultured Astrocytes ◽  
Neuronal Proteins ◽  
Dendritic Complexity ◽  
Mirna Content

In the last decades, it has been established that astrocytes play key roles in the regulation of neuronal morphology. However, the contribution of astrocyte-derived small extracellular vesicles (sEVs) to morphological differentiation of neurons has only recently been addressed. Here, we showed that cultured astrocytes expressing a GFP tagged version of the stress-regulated astrocytic enzyme Aldolase C (Aldo C-GFP) release small extracellular vesicles (sEVs) which are transferred into cultured hippocampal neurons. Surprisingly, Aldo C-GFP-containing sEVs (Aldo C-GFP sEVs) displayed an exacerbated capacity to reduce the dendritic complexity in developing hippocampal neurons compared to sEVs derived from control (i.e. GFP-expressing) astrocytes. Using bioinformatics and biochemical tools, we found that the total content of overexpressed Aldo C-GFP correlates with an increased content of endogenous miRNA-26a-5p in both total astrocyte homogenates and sEVs. Notably, neurons magnetofected with a nucleotide sequence that mimics endogenous miRNA-26a-5p (mimic 26a-5p) not only decreased the levels of neuronal proteins associated to morphogenesis regulation and also reproduced morphological changes induced by Aldo-C-GFP sEVs. Furthermore, neurons magnetofected with a sequence targeting miRNA-26a-5p (antago 26a-5p) were largely resistant to Aldo C-GFP sEVs. Our results support a novel and complex level of astrocyte-to-neuron communication mediated by astrocyte-derived sEVs and the activity of their miRNA content.

scholarly journals Hippocampal neurons with stable excitatory connectivity become part of neuronal representations

PLoS Biology ◽  
2020 ◽  
Vol 18 (11) ◽  
pp. e3000928 ◽  
Author(s):  
Tim P. Castello-Waldow ◽  
Ghabiba Weston ◽  
Alessandro F. Ulivi ◽  
Alireza Chenani ◽  
Yonatan Loewenstein ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Time Window ◽  
Structural Connectivity ◽  
Time Lapse ◽  
Early Gene ◽  
Synaptic Connectivity ◽  
Time Duration ◽  
Hippocampal Ca1 ◽  
Cornu Ammonis

Experiences are represented in the brain by patterns of neuronal activity. Ensembles of neurons representing experience undergo activity-dependent plasticity and are important for learning and recall. They are thus considered cellular engrams of memory. Yet, the cellular events that bias neurons to become part of a neuronal representation are largely unknown. In rodents, turnover of structural connectivity has been proposed to underlie the turnover of neuronal representations and also to be a cellular mechanism defining the time duration for which memories are stored in the hippocampus. If these hypotheses are true, structural dynamics of connectivity should be involved in the formation of neuronal representations and concurrently important for learning and recall. To tackle these questions, we used deep-brain 2-photon (2P) time-lapse imaging in transgenic mice in which neurons expressing the Immediate Early Gene (IEG) Arc (activity-regulated cytoskeleton-associated protein) could be permanently labeled during a specific time window. This enabled us to investigate the dynamics of excitatory synaptic connectivity—using dendritic spines as proxies—of hippocampal CA1 (cornu ammonis 1) pyramidal neurons (PNs) becoming part of neuronal representations exploiting Arc as an indicator of being part of neuronal representations. We discovered that neurons that will prospectively express Arc have slower turnover of synaptic connectivity, thus suggesting that synaptic stability prior to experience can bias neurons to become part of representations or possibly engrams. We also found a negative correlation between stability of structural synaptic connectivity and the ability to recall features of a hippocampal-dependent memory, which suggests that faster structural turnover in hippocampal CA1 might be functional for memory.

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