Inhibition of GABA A receptor improved special memory impairment in the local model of demyelination in rat hippocampus

Majd, Alireza Mousavi; Tabar, Forough Ebrahim; Afghani, Arghavan; Ashrafpour, Sahand; Dehghan, Samaneh; Gol, Mohammad; Ashrafpour, Manouchehr; Pourabdolhossein, Fereshteh

doi:10.1016/j.bbr.2017.08.046

Cited by 20 publications

(9 citation statements)

References 64 publications

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“…Animal studies have shown that maternal separation impairs prefrontal cortical myelination and cognitive functions (21). Local hippocampal demyelination induced by LPC is associated with spatial learning disability (61). Until now it has not been clear whether schema-like learning and memory retrieval require myelin plasticity.…”

Section: Discussionmentioning

confidence: 99%

Schema‐like learning and memory consolidation acting through myelination

et al. 2019

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Memory is a dynamic brain function that is continually processed after encoding. Although psychologic concepts of mental schema are now well established, they have rarely been considered in animal studies. We used a behavior paradigm of multiple flavor-place paired associates (PAs) and showed that memory schema facilitates fast acquisition of new PAs in a single trial. The hippocampus is necessary for the encoding of new PAs and for memory retrieval within a certain time window—24 h following new PA consolidation. Whereas the anterior cingulate cortex (ACC) plays a critical role for dynamic PA learning and consolidation during training sessions, ACC is essential in schema representation and activation. New myelin generation is essential for learning. Neural activity in the cortical regions impacts myelination by regulating oligodendrocyte (OL) proliferation, differentiation, and myelin formation. Here, we show that newly formed OL progenitor cells and mature OLs are increased following repeated PA learning and that establishment of the memory schema is associated with enhanced myelin strength in the ACC region. Furthermore, to ensure that myelination is necessary for the acquisition of paired-associate learning, ACC lysolecithin-induced demyelination revealed impaired PA learning associated with decrease in ACC θ band power and reduced spike-field coherence and phase-locking in ACC.—Hasan, M., Kanna, M. S., Jun, W., Ramkrishnan, A. S., Iqbal, Z., Lee, Y., Li, Y. Schema-like learning and memory consolidation acting through myelination.

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Section: Discussionmentioning

confidence: 99%

Schema‐like learning and memory consolidation acting through myelination

et al. 2019

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“…Slides were observed under an Olympus Cx-23 microscope. We captured Images from spinal cord with C-P6 OPTIKA camera and the demyelination extension was calculated as the ratio of demyelinated area/total area with Image J software (National Institutes of Health, USA) [42,43]. The images were analyzed from 12 different points of the spinal cord (100 µm interval) from coronal serial sections (6 µm).We averaged 10 sections from a single animal in each group (n = 3); therefore, 30 sections were analyzed for each experimental group.…”

Section: Histological Analysismentioning

confidence: 99%

Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects

et al. 2021

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In ammation, demyelination, glial activation, and oxidative damage are the most pathological hallmarks of multiple sclerosis (MS). Piperine, a main bioactive alkaloid of black pepper, possesses antioxidant, anti-in ammatory and neuroprotective properties whose therapeutic potential has been less studied in the experimental autoimmune encephalomyelitis (EAE) models. In this study, the e ciency of peprine on progression of EAE model and myelin repair mechanisms was investigated. EAE was induced in female Lewis rats and piperine and its vehicle were daily administrated intraperitoneally from day 8 to 29 post immunization. We found that peperine alleviated neurological de cits and EAE disease progression. Luxol fast blue and H&E staining and immuno-staining of lumbar spinal cord cross sections con rmed that piperine signi cantly reduced the extent of demyelination, in ammation and immune cell in ltration and inhibited microglia and astrocyte activation. Gene expression analysis in lumbar spinal cord showed that piperine treatment decreased the level of pro-in ammatory cytokines (TNF-α, IL-1β) and iNOS and enhanced IL-10, Nrf-2, HO-1and MBP expressions. Piperine supplementation also enhanced the total antioxidant capacity (FRAP) and reduced the level of oxidative stress marker (MDA) in the CNS of EAE rats. Finally, we found that piperine has anti-apoptotic and neuroprotective effect in EAE through reducing caspase-3 (apoptosis marker) and enhancing BDNF and NeuN expressing cells. This study strongly indicates that piperine has a bene cial effect on the EAE progression and could be considered as a potential therapeutic target for MS treatment. Upcoming clinical trials will provide the deep understanding of piperine's role for the treatment of the MS.

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“…Activation of GABA A and GABA B subunits results in hyperpolarizing influx of chloride and potassium ions respectively. In rodent models, over-activation of GABA A and GABA B receptors is known to cause learning and memory deficits, especially spatial navigation deficits, and the inhibition of GABA A 50 and GABA B 51 improves deficits in demyelination and vascular models of dementia. Studies have shown that reactive oxygen species increase the potency of GABA A , increase GABA A receptor-mediated tonic current in hippocampal neurons in rodent oxidative stress models 52 , and modulates GABA A function 53 .…”

Section: Discussionmentioning

confidence: 99%

Supraphysiological Levels of Oxygen Exposure During the Neonatal Period Impairs Signaling Pathways Required for Learning and Memory

Ramani

Kumar

Halloran

et al. 2018

Sci Rep

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Preterm infants often require prolonged oxygen supplementation and are at high risk of neurodevelopmental impairment. We recently reported that adult mice exposed to neonatal hyperoxia (postnatal day [P] 2 to 14) had spatial navigation memory deficits associated with hippocampal shrinkage. The mechanisms by which early oxidative stress impair neurodevelopment are not known. Our objective was to identify early hyperoxia-induced alterations in hippocampal receptors and signaling pathways necessary for memory formation. We evaluated C57BL/6 mouse pups at P14, exposed to either 85% oxygen or air from P2 to 14. We performed targeted analysis of hippocampal ligand-gated ion channels and proteins necessary for memory formation, and global bioinformatic analysis of differentially expressed hippocampal genes and proteins. Hyperoxia decreased hippocampal mGLU7, TrkB, AKT, ERK2, mTORC1, RPS6, and EIF4E and increased α3, α5, and ɤ2 subunits of GABAA receptor and PTEN proteins, although changes in gene expression were not always concordant. Bioinformatic analysis indicated dysfunction in mitochondria and global protein synthesis and translational processes. In conclusion, supraphysiological oxygen exposure reduced proteins necessary for hippocampus-dependent memory formation and may adversely impact hippocampal mitochondrial function and global protein synthesis. These early hippocampal changes may account for memory deficits seen in preterm survivors following prolonged oxygen supplementation.

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Inhibition of GABA A receptor improved special memory impairment in the local model of demyelination in rat hippocampus

Cited by 20 publications

References 64 publications

Schema‐like learning and memory consolidation acting through myelination

Schema‐like learning and memory consolidation acting through myelination

Piperine Improves Experimental Autoimmune Encephalomyelitis (EAE) in Lewis Rats Through its Neuroprotective, Anti-inflammatory, and Antioxidant Effects

Supraphysiological Levels of Oxygen Exposure During the Neonatal Period Impairs Signaling Pathways Required for Learning and Memory

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