Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

Silva, Bruno; Sousa, Larissa Fonseca da Cunha; Miranda, Aline Silva de; Vasconcelos, A. B. de; Reis, Helton José; Barcelos, Lucíola da Silva; Arantes, Rosa Maria Esteves; Rachid, Milene Alvarenga

doi:10.1590/0004-282x20150083

Cited by 40 publications

(28 citation statements)

References 24 publications

(20 reference statements)

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“…Interestingly, there was a notable increase in plasma hcy level and significant decrease in serum BDNF level in amnestic mild cognitive impairment patients that converts to AD patients, especially in those with the APOE ε4 allele [43]. Cognitive impairment is also closely related to inflammatory responses, which is highly regulated by many factors, including NFkB pathway [44], [45]. Exacerbated activation of calpain has been implicated as a major component in the signaling cascade that leads to β-amyloid (Aβ) production and tau hyperphosphorylation in AD, leading to a hypothesis that selective calpain inhibitors are potential therapeutic strategies for AD [46], [47].…”

Section: Discussionmentioning

confidence: 99%

Homocysteine-lowering gene therapy rescues signaling pathways in brain of mice with intermediate hyperhomocysteinemia

et al. 2018

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Hyperhomocysteinemia due to cystathionine beta synthase (CBS) deficiency is associated with diverse cognitive dysfunction. Considering the role of the serine/threonine kinase DYRK1A, not only in developmental defects with life-long structural and functional consequences, but also in multiple neurodegenerative diseases, its protein expression and kinase activity has been analyzed in brain of heterozygous CBS deficient mice and found to be increased. We previously demonstrated that specific liver treatment with an adenovirus expressing Dyrk1A normalizes hepatic DYRK1A level and decreases hyperhomocysteinemia in mice with moderate to intermediate hyperhomocysteinemia. We here use a hepatocyte-specific recombinant adeno-associated viral (AAV) serotype 8-mediated DYRK1A gene therapy (AAV2/8-DYRK1A) to analyze the effect of hepatic Dyrk1A gene transfer on some altered molecular mechanisms in brain of mice with intermediate hyperhomocysteinemia. Our selective hepatic treatment alleviates altered DYRK1A protein level and signaling pathways in brain of mice, the MAPK/ERK and PI3K/Akt pathways initiated by receptor tyrosine kinase, the BDNF dependent TrkB pathway, and NFkB pathway. These results demonstrate the positive effect of AAV2/8-DYRK1A gene transfer on neuropathological and inflammatory processes in brain of mice with intermediate hyperhomocysteinemia.

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Section: Discussionmentioning

confidence: 99%

Homocysteine-lowering gene therapy rescues signaling pathways in brain of mice with intermediate hyperhomocysteinemia

et al. 2018

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“…This confirmed neuro-inflammation by MSG. Activation of microglia in hippocampus results in releasing many neuro-inflammatory mediators such as TNF-α, IL-1β and NF-κB [8]. In addition, microglial activation can induce an inflammatory-oxidative cascade leading to cognitive deficit [30].…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the over-expression of these cytokines in the CNS is associated with behavioral and cognitive impairment in several pathological conditions. Anti-inflammatory management seems effective on cognitive deficit [8]. However, the molecular mechanisms of MSG-induced learning and memory impairments can alter the levels of some neurotransmitters and activity of neurotransmitter metabolism related enzymes, such as acetyl cholinesterase (AChE) and dopamine β-hydroxylase, in the brain [9].…”

Section: Introductionmentioning

confidence: 99%

Curcumin Protects against Monosodium Glutamate Neurotoxicity and Decreasing NMDA2B and mGluR5 Expression in Rat Hippocampus

Khalil

Khedr

2016

Neurosignals

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Background: Monosodium glutamate (MSG) is a flavor enhancer used in food industries. MSG is well documented to induce neurotoxicity. Curcumin (CUR) reportedly possesses beneficial effects against various neurotoxic insults. Hence, this present study has been designed to evaluate the neuroprotective effect of curcumin on MSG-induced neurotoxicity in rats. Methods: Thirty-two male Wister rats were divided into four groups (n=8): Control group, MSG group, CUR group and MSG + CUR group. CUR (Curcumin 150 mg/kg, orally) was given day after day for four weeks along with MSG (4 mg/kg, orally). After 4 weeks, rats were sacrificed and brain hippocampus was isolated immediately on ice. Inflammatory marker TNFα and acetylcholinesterase (AChE) activity (marker for cholinergic function) were estimated. Gene expressions of metabotropic glutamate receptor 5 (mGluR5) and N-methyl-D-aspartate receptor 2B (NMDA2B) along with glutamate concentration were assessed. Results: Treatment with CUR significantly attenuated AChE activity and TNFα in MSG-treated animals. The anti-inflammatory properties of CUR may be responsible for this observed neuroprotective action. A possible role of CUR to attenuate both glutamate level and gene expression of NMDA2B and mGLUR5 in brain hippocampus was established when compared to MSG group. Conclusion: We concluded that CUR as flavor enhancer protects against MSG-induced neurotoxicity in rats.

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“…Other cellular manifestations of neuroimmune activation include the expression of the chemokine CINC-1, the rodent homolog of human IL-8 (Ballendine et al, 2015; Silva et al, 2015), which is responsible for mediating the recruitment of neutrophils (Shibata, 2002; Brochu et al, 2011). CINC-1 was the only detectable chemokine, and one reason may be that neutrophils are the first inflammatory cells to be expressed (Witko-Sarsat et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems

Oliveira

Gouveia

Castro

et al. 2016

Front. Behav. Neurosci.

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The avoidance response is present in pathological anxiety and interferes with normal daily functions. The aim of this article is to shed light on performance markers of active avoidance (AA) using two different rat strains, Sprague-Dawley (SD) and Wistar. Specifically, good and poor performers were evaluated regarding anxiety traits exhibited in the elevated plus maze (EPM) and corticosterone levels and motor activity in the open field test. In addition, the plasma levels of Interleukin-6 (IL-6), Interleukin-1Beta (IL-1beta), Nerve Growth Factor Beta (NGF-beta), Tumor Necrosis Factor-Alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were compared in the good and poor performers to better understand the role of the immunologic system in aversive learning. Behavioral criteria were employed to identify subpopulations of SD and Wistar rats based on their behavioral scores during a two-way AA test. The animals were tested for anxiety-like behavior in the EPM and motor activity in the open-field test. Plasma corticosterone levels were measured at the end of the avoidance test. Cytokine levels of IL-6, IL-1beta, NGF-beta, TNF-alpha, and CINC-1 were measured in the plasma of the Wistar rats. Sixty-six percent of the Wistar rats and 35% of the SD rats exhibited a poor performance. This feature was associated with a decrease in anxiety-like behavior in the EPM. The poor and good performers exhibited lower levels of corticosterone compared with the control animals, which suggests that training alters corticosterone levels, thereby leading to hypocortisolism, independent of the performance. The CINC-1 levels were increased in the poor performers, which reinforces the role of immunologic system activation in learning deficits. Our study provides a better understanding of the complex interactions that underlie neuroimmune consequences and their implications for performance.

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Memory deficit associated with increased brain proinflammatory cytokine levels and neurodegeneration in acute ischemic stroke

Cited by 40 publications

References 24 publications

Homocysteine-lowering gene therapy rescues signaling pathways in brain of mice with intermediate hyperhomocysteinemia

Homocysteine-lowering gene therapy rescues signaling pathways in brain of mice with intermediate hyperhomocysteinemia

Curcumin Protects against Monosodium Glutamate Neurotoxicity and Decreasing NMDA2B and mGluR5 Expression in Rat Hippocampus

A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems

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