Microglial process convergence on axonal segments in health and disease

Benusa, Savannah D.; Lafrenaye, Audrey D.

doi:10.20517/2347-8659.2019.28

Cited by 14 publications

(14 citation statements)

References 186 publications

(339 reference statements)

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“…Microglial changes occur in association with various neuroinflammatory diseases, and in the case of multiple sclerosis, several types of microglia (or infiltrating monocytes) abnormally surround the axon, wrapping the axon initial segment of neurons and appearing to be in contact with the neuronal cell bodies. 30 The present findings that some microglia contact the degenerating neurons in the vacuolar structures might also reflect a similar phenomenon to microglial-neuronal contact in the hydrocephalic neocortex. This points the possibility that the brain of hydrocephalic cotton rats has more or less impaired projections from the neocortex.…”

Section: Discussionsupporting

confidence: 65%

Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms

et al. 2021

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Normal-pressure hydrocephalus (NPH) is a condition in which the ventricle is enlarged without elevated cerebrospinal fluid pressure, and it generally develops in later life and progresses slowly. A complete animal model that mimics human idiopathic NPH has not yet been established, and the onset mechanisms and detailed pathomechanisms of NPH are not fully understood. Here, we demonstrate a high spontaneous prevalence (34.6%) of hydrocephalus without clinical symptoms in inbred cotton rats (Sigmodon hispidus). In all 46 hydrocephalic cotton rats, the severity was mild or moderate and not severe. The dilation was limited to the lateral ventricles, and none of the hemorrhage, ventriculitis, meningitis, or tumor formation was found in hydrocephalic cotton rats. These findings indicate that the type of hydrocephalus in cotton rats is similar to that of communicating idiopathic NPH. Histopathological examinations revealed that the inner granular and pyramidal layers (layers IV and V) of the neocortex became thinner in hydrocephalic brains. A small number of pyramidal cells were positive for Fluoro-Jade C (a degenerating neuron marker) and ionized calcium-binding adaptor molecule 1 (Iba1)-immunoreactive microglia were in contact with the degenerating neurons in the hydrocephalic neocortex, suggesting that hydrocephalic cotton rats are more or less impaired projections from the neocortex. This study highlights cotton rats as a candidate for novel models to elucidate the pathomechanism of idiopathic NPH. Additionally, cotton rats have some noticeable systemic pathological phenotypes, such as chronic kidney disease and metabolic disorders. Thus, this model might also be useful for researching the comorbidities of NPH to other diseases.

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Section: Discussionsupporting

confidence: 65%

Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms

et al. 2021

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“…While the mitochondrial pathway of apoptosis is often associated with oxi dative stress at the cellular level, then the extrinsic pathway is activated due to a damage or cellular immune response [18]. Microglia can function as a substrate of cellular immunity in the brain, and its activation leads to the secretion of pro inflam matory factors in nervous tissue and causes neu roinflammation and apoptosis [19].…”

Section: Introductionmentioning

confidence: 99%

Markers of Neuroinflammation and Apoptosis in the Temporal Lobe of Patients with Drug-Resistant Epilepsy

Литовченко

Zabrodskaya

Sitovskaya

et al. 2021

J Evol Biochem Phys

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Current antiepileptic strategies aim to normalize the interaction of the excitatory and inhibitory systems, which is ineffective in treating patients with drug-resistant epilepsy. Neuroinflammatory processes in the epileptic focus and its perifocal area can trigger apoptosis and also contribute to the development of drug resistance. The level of pro- and anti-apoptotic proteins (p-NF-kB, TNF-α, p53, FAS, caspase-3, caspase-9) was analyzed in intraoperative biopsies of the temporal lobe gray and white matter in the brain of patients with drug-resistant epilepsy. An increased level of pro-apoptotic proteins was revealed in the cortex and perifocal area’s white matter against the background of an imbalance of protective anti-apoptotic proteins. It appears that the activation of the extrinsic pathway of apoptosis occurs in the perifocal area, while in the epileptic focus, there are proteins responsible for the activation of the anti-apoptotic survival pathways. Active neuroinflammation in the epileptic focus and perifocal area of the temporal lobe may contribute to the development of the resistance to antiepileptic drugs and the progression of neurodegeneration in such patients.

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“…Increased extracellular water content is a biomarker of neuroinflammation, 66 and micro glia aid in engulfing axonal debris. 67,68 Therefore, we chose AD as the primary DTI index of interest for our analysis.…”

Section: J Psychiatry Neurosci 2022;47(3)mentioning

confidence: 99%

The functional and structural associations of aberrant microglial activity in major depressive disorder

Cakmak

Liu

Poirier

et al. 2022

jpn

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Background: Major depressive disorder (MDD) is a debilitating mental illness that has been linked to increases in markers of inflammation, as well as to changes in brain functional and structural connectivity, particularly between the insula and the subgenual anterior cingulate cortex (sgACC). In this study, we directly related inflammation and dysconnectivity in treatment-resistant MDD by concurrently measuring the following: microglial activity with [ 18 F]N-2-(fluoroethoxyl)benzyl-N-(4phenoxypyridin-3-yl)acetamide ([ 18 F]FEPPA) positron emission tomography (PET); the severity of MDD; and functional or structural connectivity among insula or sgACC nodes. Methods: Twelve patients with treatment-resistant MDD (8 female, 4 male; mean age ± standard deviation 54.9 ± 4.5 years and 23 healthy controls (11 female, 12 male; 60.3 ± 8.5 years) completed a hybrid [ 18 F]FEPPA PET and MRI acquisition. From these, we extracted relative standardized uptake values for [ 18 F]FEPPA activity and Pearson r-to-z scores representing functional connectivity from our regions of interest. We extracted diffusion tensor imaging metrics from the cingulum bundle, a key white matter bundle in MDD. We performed regressions to relate microglial activity with functional connectivity, structural connectivity and scores on the 17-item Hamilton Depression Rating Scale. Results: We found significantly increased [ 18 F]FEPPA uptake in the left sgACC in patients with treatment-resistant MDD compared to healthy controls. Patients with MDD also had a reduction in connectivity between the sgACC and the insula. The [ 18 F]FEPPA uptake in the left sgACC was significantly related to functional connectivity with the insula, and to the structural connectivity of the cingulum bundle.[ 18 F]FEPPA uptake also predicted scores on the Hamilton Depression Rating Scale. Limitations: A relatively small sample size, lack of functional task data and concomitant medication use may have affected our findings. Conclusion: We present preliminary evidence linking a network-level dysfunction relevant to the pathophysiology of depression and related to increased microglial activity in MDD.

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Microglial process convergence on axonal segments in health and disease

Cited by 14 publications

References 186 publications

Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms

Cotton rats (Sigmodon hispidus) with a high prevalence of hydrocephalus without clinical symptoms

Markers of Neuroinflammation and Apoptosis in the Temporal Lobe of Patients with Drug-Resistant Epilepsy

The functional and structural associations of aberrant microglial activity in major depressive disorder

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