Modulation of CREB and its associated upstream signaling pathways in pesticide-induced neurotoxicity

Narasimhamurthy, Rekha Koravadi; Andrade, Daicy; Mumbrekar, Kamalesh Dattaram

doi:10.1007/s11010-022-04472-7

Cited by 15 publications

(14 citation statements)

References 91 publications

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“…All proteins were quantified by western blot analyses for the samples that were collected 30 min or 1 h after the injection. In addition, pCREB and total CREB were quantified for the samples up to 4 h after the injection because CREB exists in the nucleus and reportedly shown to be activated a few hours after a stimulation such as learning [11]. Figure 4 shows the effects of MEL and AMK on the relative phosphorylation levels (RPLs) of CREB.…”

Section: Resultsmentioning

confidence: 99%

“…Activations of several intracellular protein kinases such as cyclic AMP-dependent protein kinase (PKA), protein kinase B (AKT), protein kinase C (PKC), extracellular-regulated protein kinases (ERKs) and Ca 2+ /calmodulin-dependent protein kinases (CaMKs) play an essential role in synaptic plasticity such as long-term potentiation [10,11]. Activation of these kinases is involved not only in establishing short-term memory by altering ion channel properties or ion channel density but also in establishing long-term memory by activating cAMP-response element-binding protein (CREB) [10,11]. The CREB phosphorylation induces gene expression and protein synthesis necessary for structural changes at existing synapses as well as synaptogenesis.…”

Section: Introductionmentioning

confidence: 99%

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N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation

et al. 2023

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Objectives Melatonin (MEL) has been reported to enhance cognitive performance. Recently, we have demonstrated that a MEL metabolite N-acetyl-5methoxykynuramine (AMK) promoted the formation of long-term object recognition memory more potently than MEL. Here, we examined the effects of 1 mg/kg MEL and AMK on both object location memory and spatial working memory. We also investigated the effects of the same dose of these drugs on relative phosphorylation/activation levels of memory-related proteins in the hippocampus (HP), the perirhinal cortex (PRC) and the medial prefrontal cortex (mPFC).Methods Object location memory and spatial working memory were assessed using the object location task and the Y-maze spontaneous alternation task, respectively. Relative phosphorylation/activation levels of memoryrelated proteins were assessed using western blot analysis.Results AMK, as well as MEL, enhanced object location memory and spatial working memory. AMK increased the phosphorylation of cAMP-response element-binding protein (CREB) in both the HP and the mPFC 2 h after the treatment. AMK also increased the phosphorylation of extracellular signal-regulated kinases (ERKs) but decreased that of Ca 2+ /calmodulindependent protein kinases II (CaMKIIs) in the PRC and the mPFC 30 min after the treatment. MEL increased CREB phosphorylation in the HP 2 h after the treatment, whereas no detectable changes in the other proteins examined were observed. ConclusionThese results suggested the possibility that AMK exerts stronger memory-enhancing effects than MEL by more remarkably altering the activation of memory-related proteins such as ERKs, CaMKIIs and CREB in broader brain regions, including the HP, mPFC and PRC, compared to MEL.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation

et al. 2023

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“…These effects include changes to cellular signaling pathways, with notable implications for processes like Camp response element binding protein (CREB) phosphorylation. [ 97 ] CREB stands as a pivotal transcription factor with multifaceted involvement in essential cellular functions such as memory and learning, neuronal plasticity, and stress response. Activation of CREB is intricately associated with the protein kinase A (PKA) pathway, a regulatory cascade influenced by cyclic adenosine monophosphate (cAMP) levels.…”

Section: Effect Of Opps On Glial Cellsmentioning

confidence: 99%

“…As a result, this can perturb the phosphorylation of CREB, subsequently impacting downstream patterns of gene expression and cellular responses. [ 97 ] Altered CREB phosphorylation can profoundly impact cellular functions, including gene expression changes that influence neuroplasticity, memory, and the response to stress. Also, such disruptions in CREB signaling are linked to various neurological and neuropsychiatric disorders.…”

Section: Effect Of Opps On Glial Cellsmentioning

confidence: 99%

Implications of organophosphate pesticides on brain cells and their contribution toward progression of Alzheimer's disease

Yadav,

Kaur,

Yadav

et al. 2024

J Biochem & Molecular Tox

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The most widespread neurodegenerative disorder, Alzheimer's disease (AD) is marked by severe behavioral abnormalities, cognitive and functional impairments. It is inextricably linked with the deposition of amyloid β (Aβ) plaques and tau protein in the brain. Loss of white matter, neurons, synapses, and reactive microgliosis are also frequently observed in patients of AD. Although the causative mechanisms behind the neuropathological alterations in AD are not fully understood, they are likely influenced by hereditary and environmental factors. The etiology and pathogenesis of AD are significantly influenced by the cells of the central nervous system, namely, glial cells and neurons, which are directly engaged in the transmission of electrical signals and the processing of information. Emerging evidence suggests that exposure to organophosphate pesticides (OPPs) can trigger inflammatory responses in glial cells, leading to various cascades of events that contribute to neuroinflammation, neuronal damage, and ultimately, AD pathogenesis. Furthermore, there are striking similarities between the biomarkers associated with AD and OPPs, including neuroinflammation, oxidative stress, dysregulation of microRNA, and accumulation of toxic protein aggregates, such as amyloid β. These shared markers suggest a potential mechanistic link between OPP exposure and AD pathology. In this review, we attempt to address the role of OPPs on altered cell physiology of the brain cells leading to neuroinflammation, mitochondrial dysfunction, and oxidative stress linked with AD pathogenesis.

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“…Significant downregulation of BDNF mRNA, resulting in a 50% reduction of available BDNF protein [72,74], occurs in AD. CREB, a transcriptional regulator of BDNF and a downstream mediator of its activity [75][76][77][78], is also reduced in AD. In glutamate-stimulated hippocampal neurons treated with toxic oligomeric Aβ42, there is a significant decrease in the activity of PKA, which leads to decreased activation of CREB [79].…”

Section: Role Of Brain-derived Neurotrophic Factormentioning

confidence: 99%

Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer’s Disease

Jaberi,

Fahnestock

2023

Biomolecules

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Brain-derived neurotrophic factor (BDNF) is a key molecule in promoting neurogenesis, dendritic and synaptic health, neuronal survival, plasticity, and excitability, all of which are disrupted in neurological and cognitive disorders such as Alzheimer’s disease (AD). Extracellular aggregates of amyloid-β (Aβ) in the form of plaques and intracellular aggregates of hyperphosphorylated tau protein have been identified as major pathological insults in the AD brain, along with immune dysfunction, oxidative stress, and other toxic stressors. Although aggregated Aβ and tau lead to decreased brain BDNF expression, early losses in BDNF prior to plaque and tangle formation may be due to other insults such as oxidative stress and contribute to early synaptic dysfunction. Physical exercise, on the other hand, protects synaptic and neuronal structure and function, with increased BDNF as a major mediator of exercise-induced enhancements in cognitive function. Here, we review recent literature on the mechanisms behind exercise-induced BDNF upregulation and its effects on improving learning and memory and on Alzheimer’s disease pathology. Exercise releases into the circulation a host of hormones and factors from a variety of peripheral tissues. Mechanisms of BDNF induction discussed here are osteocalcin, FNDC5/irisin, and lactate. The fundamental mechanisms of how exercise impacts BDNF and cognition are not yet fully understood but are a prerequisite to developing new biomarkers and therapies to delay or prevent cognitive decline.

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Modulation of CREB and its associated upstream signaling pathways in pesticide-induced neurotoxicity

Cited by 15 publications

References 91 publications

N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation

N-acetyl-5-methoxykynuramine enhance object location and working memory performances via modulating CaMKII, ERK and CREB phosphorylation

Implications of organophosphate pesticides on brain cells and their contribution toward progression of Alzheimer's disease

Mechanisms of the Beneficial Effects of Exercise on Brain-Derived Neurotrophic Factor Expression in Alzheimer’s Disease

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