Microgliosis is associated with visual memory decline in patients with temporal lobe epilepsy and hippocampal sclerosis: A clinicopathologic study

Toscano, Eliana Cristina de Brito; Vieira, Érica Leandro Marciano; Portela, Ana Carolina Diniz Carvalho; Caliari, Marcelo Vidigal; Brant, Joseane Aparecida Sousa; Giannetti, Alexandre Varella; Suemoto, Cláudia Kimie; Leite, Renata Elaine Paraízo; Nitrini, Ricardo; Rachid, Milene Alvarenga; Teixeira, Antônio Lúcio

doi:10.1016/j.yebeh.2019.106643

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…Hippocampal sclerosis with neuronal loss and gliosis is characteristic of both patients with TLE [87] and experimental animals in TLE models [60,88]. In TLE models, reactive astrogliosis and microgliosis have also been reported in the piriform cortex [89], amygdala, and entorhinal cortex [90].…”

Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Zubareva,

Dyomina,

Kovalenko

et al. 2023

IJMS

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Epilepsy is a challenging brain disorder that is often difficult to treat with conventional therapies. The gut microbiota has been shown to play an important role in the development of neuropsychiatric disorders, including epilepsy. In this study, the effects of Bifidobacterium longum, a probiotic, on inflammation, neuronal degeneration, and behavior are evaluated in a lithium–pilocarpine model of temporal lobe epilepsy (TLE) induced in young adult rats. B. longum was administered orally at a dose of 109 CFU/rat for 30 days after pilocarpine injection. The results show that B. longum treatment has beneficial effects on the TLE-induced changes in anxiety levels, neuronal death in the amygdala, and body weight recovery. In addition, B. longum increased the expression of anti-inflammatory and neuroprotective genes, such as Il1rn and Pparg. However, the probiotic had little effect on TLE-induced astrogliosis and microgliosis and did not reduce neuronal death in the hippocampus and temporal cortex. The study suggests that B. longum may have a beneficial effect on TLE and may provide valuable insights into the role of gut bacteria in epileptogenesis. In addition, the results show that B. longum may be a promising drug for the comprehensive treatment of epilepsy.

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Section: Discussionmentioning

confidence: 99%

Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Zubareva,

Dyomina,

Kovalenko

et al. 2023

IJMS

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“…The functional role of GFAP in astrocytes has been widely accepted, which is involved in the process of regeneration, synaptic remodeling, and reactive gliosis [ 37 , 38 ]. Hippocampal sclerosis is the most common feature in TLE, which is due to the proliferation and hypertrophy of astrocytes resulted from increased glia-associated proteins [ 39 , 40 ]. An increased GFAP and typical gliosis have been observed within the hippocampus in our present research, which further consolidate the insight that increased GFAP is involved in hippocampal gliosis and epileptogenesis.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy

Ding

Zhao

et al. 2022

Neural Plasticity

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Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC–MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and P < 0.05 . Bioinformatics analysis indicated 27 DEPs were mainly enriched in “regulation of synaptic plasticity and structure” and “calmodulin-dependent protein kinase activity,” which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-β, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.

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“…In general, the functions of microglia include phagocytosis of apoptotic cells, pathogens, Aβ, and synapses/synaptic pruning, and secretion of cytokines/chemokines or protective factors. In FAD mice and AD patients, there are higher numbers of Iba1-positive cells, which likely represents migration of microglia to the area, or potentially infiltration and differentiation of peripheral immune cells ( Hein and O’Banion, 2009 ; Balducci et al, 2018 ; Toscano et al, 2020 ). In addition to number, the activation of microglia is associated with a morphological shift in appearance from small cell somas and long processes to large cell bodies with fewer and shorter processes ( Schlachetzki and Hull, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Systemic Candesartan Treatment Modulates Behavior, Synaptic Protein Levels, and Neuroinflammation in Female Mice That Express Human APOE4

et al. 2021

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Evidence suggests that angiotensin receptor blockers (ARBs) could be beneficial for Alzheimer’s disease (AD) patients independent of any effects on hypertension. However, studies in rodent models directly testing the activity of ARB treatment on behavior and AD-relevent pathology including neuroinflammation, Aβ levels, and cerebrovascular function, have produced mixed results. APOE4 is a major genetic risk factor for AD and has been linked to many of the same functions as those purported to be modulated by ARB treatment. Therefore, evaluating the effects of ARB treatment on behavior and AD-relevant pathology in mice that express human APOE4 could provide important information on whether to further develop ARBs for AD therapy. In this study, we treated female and male mice that express the human APOE4 gene in the absence (E4FAD−) or presence (E4FAD+) of high Aβ levels with the ARB prodrug candesartan cilexetil for a duration of 4 months. Compared to vehicle, candesartan treatment resulted in greater memory-relevant behavior and higher hippocampal presynaptic protein levels in female, but not male, E4FAD− and E4FAD+ mice. The beneficial effects of candesartan in female E4FAD− and E4FAD+ mice occurred in tandem with lower GFAP and Iba1 levels in the hippocampus, whereas there were no effects on markers of cerebrovascular function and Aβ levels. Collectively, these data imply that the effects of ARBs on AD-relevant pathology may be modulated in part by the interaction between APOE genotype and biological sex. Thus, the further development of ARBs could provide therapeutic options for targeting neuroinflammation in female APOE4 carriers.

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Microgliosis is associated with visual memory decline in patients with temporal lobe epilepsy and hippocampal sclerosis: A clinicopathologic study

Cited by 6 publications

References 33 publications

Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Beneficial Effects of Probiotic Bifidobacterium longum in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats

Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy

Systemic Candesartan Treatment Modulates Behavior, Synaptic Protein Levels, and Neuroinflammation in Female Mice That Express Human APOE4

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