Amyloid Beta Alters Prefrontal-dependent Functions Along with its Excitability and Synaptic Plasticity in Male Rats

Torres-Flores, Mayra; Peña‐Ortega, Fernando

doi:10.1016/j.neuroscience.2022.07.006

Cited by 9 publications

(18 citation statements)

References 105 publications

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“…Rats were anesthetized with a mixture of Ketamine/Xylazine (80 mg/kg and 10 mg/kg, respectively, i.p.) and placed in a stereotaxic frame (Stoelting Co., IL) for surgery [ 43 ]. After cleansing the skin with povidone-iodine solution, an incision was made, and a burr hole was drilled into the skull 2.5 mm lateral to the midline and 0.3 mm posterior to Bregma [ 44 ].…”

Section: Methodsmentioning

confidence: 99%

“…Using a 10 μL Hamilton syringe, 5 x 10 5 C6 cells in 5 μL Hank’s Balanced Salt Solution were microinjected into the right striatum, with an injection pump, at a rate of 0.5 μL/min. The needle was kept in place for 5 minutes after the injection was completed to avoid reflux of the cell suspension through the needle path [ 43 ]. The skin was sutured, and analgesics and saline were administered intraperitoneally to prevent infection and dehydration.…”

Section: Methodsmentioning

confidence: 99%

“…Up to 2 h after the MRI session, rats were anesthetized with a mixture of Ketamine/Xylazine (80 mg/kg and 10 mg/kg, respectively, i.p.) and intracardially perfused with 0.01 M phosphate-buffered saline (PBS), followed by with 4% paraformaldehyde (PFA) in PBS [ 2 , 43 , 48 , 49 ]. The brain was removed and incubated in 4% PFA overnight.…”

Section: Methodsmentioning

confidence: 99%

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Morphological differentiation of peritumoral brain zone microglia

Salas-Gallardo,

Lorea-Hernández,

Robles-Gómez

et al. 2024

PLoS ONE

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The Peritumoral Brain Zone (PBZ) contributes to Glioblastoma (GBM) relapse months after the resection of the original tumor, which is influenced by a variety of pathological factors. Among those, microglia are recognized as one of the main regulators of GBM progression and probably relapse. Although microglial morphology has been analyzed inside GBM and its immediate surroundings, it has not been objectively characterized throughout the PBZ. Thus, we aimed to perform a thorough characterization of microglial morphology in the PBZ and its likely differentiation not just from the tumor-associated microglia but from control tissue microglia. For this purpose, Sprague Dawley rats were intrastriatally implanted with C6 cells to induce a GBM formation. Gadolinium-based magnetic resonance imaging (MRI) was performed to locate the tumor and to define the PBZ (2 mm beyond the tumor border), thus delimitating the different regions of interest (ROIs: core tumoral zone and immediate interface; contralateral striatum as control). Brain slices were obtained and immunolabeled with the microglia marker Iba-1. Sixteen morphological parameters were measured for each cell, significative differences were found in all parameters when comparing the four ROIs. To determine if PBZ microglia could be morphologically differentiated from microglia in other ROIs, hierarchical clustering analysis was performed, revealing that microglia can be separated into four morphologically differentiated clusters, each of them mostly integrated by cells sampled in each ROI. Furthermore, a classifier based on linear discriminant analysis, including only three morphological parameters, categorized microglial cells across the studied ROIs and showed a gradual transition between them. The robustness of this classification was assessed through principal component analysis with the remaining 13 morphological parameters, corroborating the obtained results. Thus, in this study we provided objective and quantitative evidence that PBZ microglia represent a differentiable microglial morphotype that could contribute to the recurrence of GBM in this area.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Morphological differentiation of peritumoral brain zone microglia

Salas-Gallardo,

Lorea-Hernández,

Robles-Gómez

et al. 2024

PLoS ONE

Self Cite

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“…Many studies have focused on the influence of microglia on long-term potentiation (LTP) and long-term depression (LTD) [42,43,[200][201][202] (Figure 1). LTP and LTD are forms of long-term neuronal plasticity [99,203,204] that consist in a long-term increase or decrease in synaptic efficacy, respectively, that have been closely associated with learning and memory, among other changes in behavioral adaptations [99,203,204]. The absence of microglia has been related to differential disturbances in hippocampal LTP [45,193].…”

Section: Fractalkine/cx3cr1 Modulation Of Neuronal Plasticitymentioning

confidence: 99%

Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease

Camacho-Hernández

Peña‐Ortega

2023

Neural Plasticity

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CX3CR1 is a G protein-coupled receptor that is expressed exclusively by microglia within the brain parenchyma. The only known physiological CX3CR1 ligand is the chemokine fractalkine (FKN), which is constitutively expressed in neuronal cell membranes and tonically released by them. Through its key role in microglia-neuron communication, the FKN/CX3CR1 axis regulates microglial state, neuronal survival, synaptic plasticity, and a variety of synaptic functions, as well as neuronal excitability via cytokine release modulation, chemotaxis, and phagocytosis. Thus, the absence of CX3CR1 or any failure in the FKN/CX3CR1 axis has been linked to alterations in different brain functions, including changes in synaptic and network plasticity in structures such as the hippocampus, cortex, brainstem, and spinal cord. Since synaptic plasticity is a basic phenomenon in neural circuit integration and adjustment, here, we will review its modulation by the FKN/CX3CR1 axis in diverse brain circuits and its impact on brain function and adaptation in health and disease.

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“…A recent study conducted by Torres-Flores, and Pena-Ortega (2022) has revealed that Aβ disturbs synaptic plasticity in male rats and affects prefrontal cortex-dependent functions that include working memory and cognitive flexibility. The study evaluated the effects of Aβ injection into the prefrontal cortex, and it has been observed that a single Aβ injection learning and performance of animals in delayed nonmatching to sample test that is used to check working memory in animals [ 65 ].…”

Section: Amyloid Beta Precursor Protein Processingmentioning

confidence: 99%

Amyloid Beta in Aging and Alzheimer’s Disease

Sehar

Rawat

Reddy

et al. 2022

IJMS

138

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Alzheimer’s disease (AD), is a progressive neurodegenerative disease that affects behavior, thinking, learning, and memory in elderly individuals. AD occurs in two forms, early onset familial and late-onset sporadic; genetic mutations in PS1, PS2, and APP genes cause early onset familial AD, and a combination of lifestyle, environment and genetic factors causes the late-onset sporadic form of the disease. However, accelerated disease progression is noticed in patients with familial AD. Disease-causing pathological changes are synaptic damage, and mitochondrial structural and functional changes, in addition to increased production and accumulation of phosphorylated tau (p-tau), and amyloid beta (Aβ) in the affected brain regions in AD patients. Aβ is a peptide derived from amyloid precursor protein (APP) by proteolytic cleavage of beta and gamma secretases. APP is a glycoprotein that plays a significant role in maintaining neuronal homeostasis like signaling, neuronal development, and intracellular transport. Aβ is reported to have both protective and toxic effects in neurons. The purpose of our article is to summarize recent developments of Aβ and its association with synapses, mitochondria, microglia, astrocytes, and its interaction with p-tau. Our article also covers the therapeutic strategies that reduce Aβ toxicities in disease progression and discusses the reasons for the failures of Aβ therapeutics.

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Amyloid Beta Alters Prefrontal-dependent Functions Along with its Excitability and Synaptic Plasticity in Male Rats

Cited by 9 publications

References 105 publications

Morphological differentiation of peritumoral brain zone microglia

Morphological differentiation of peritumoral brain zone microglia

Fractalkine/CX3CR1-Dependent Modulation of Synaptic and Network Plasticity in Health and Disease

Amyloid Beta in Aging and Alzheimer’s Disease

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