Changes in oxidative metabolism and memory and learning in a cerebral hypoperfusion model in rats

Guerrero, Y. Castaño; Fraguela, María Elena González; Verdecia, Ivette Fernández; Gutiérrez, I. Horruitiner; Carpio, S. Piedras

doi:10.1016/j.nrleng.2012.01.001

Cited by 2 publications

(1 citation statement)

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“…Regardless of the disease state, the conversion of NO to ONOO∙− reduces NO levels, and in turn, the ability of NO to regulate CBF (Druhan et al, 2008). Loss of vasoregulation in the brain, leads to severe consequences such as tissue damage and neurocognitive decline due to a lack of proper blood supply which is compounded by a lack of recurrent blood flow to vulnerable deeper brain structures (i.e., the hippocampus) (Castano Guerrero et al, 2013; de la Torre, 2000b). Such tissue loss is also congruent with the observation of ventricular enlargement seen in both human and rodent AD pathologies (de la Torre, 2000a; Tosun et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease

Clemons

Acosta

Udo

et al. 2022

Journal Cellular Physiology

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Alzheimer's disease (AD) is the leading cause of mortality, disability, and long‐term care burden in the United States, with women comprising the majority of AD diagnoses. While AD‐related dementia is associated with tau and amyloid beta accumulation, concurrent derangements in cerebral blood flow have been observed alongside these proteinopathies in humans and rodent models. The homeostatic production of nitric oxide synthases (NOS) becomes uncoupled in AD which leads to decreased NO‐mediated vasodilation and oxidative stress via the production of peroxynitrite (ONOO−∙) superoxide species. Here, we investigate the role of the novel protein arginine methyltransferase 4 (PRMT4) enzyme function and its downstream product asymmetric dimethyl arginine (ADMA) as it relates to NOS dysregulation and cerebral blood flow in AD. ADMA (type‐1 PRMT product) has been shown to bind NOS as a noncanonic ligand causing enzymatic dysfunction. Our results from RT‐qPCR and protein analyses suggest that aged (9−12 months) female mice bearing tau‐ and amyloid beta‐producing transgenic mutations (3xTg‐AD) express higher levels of PRMT4 in the hippocampus when compared to age‐ and sex‐matched C57BL6/J mice. In addition, we performed studies to quantify the expression and activity of different NOS isoforms. Furthermore, laser speckle contrast imaging analysis was indicative that 3xTg‐AD mice have dysfunctional NOS activity, resulting in reduced production of NO metabolites, enhanced production of free‐radical ONOO−, and decreased cerebral blood flow. Notably, the aforementioned phenomena can be reversed via pharmacologic PRMT4 inhibition. Together, these findings implicate the potential importance of PRMT4 signaling in the pathogenesis of Alzheimer's‐related cerebrovascular derangement.

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Section: Introductionmentioning

confidence: 99%

Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease

Clemons

Acosta

Udo

et al. 2022

Journal Cellular Physiology

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Cholinergic modulation of hippocampal long-term potentiation in chronic cerebral hypoperfused rats

et al. 2018

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Vascular dementia (VaD) is one of the most common types of dementia in Alzheimer’s disease (AD). Two-vessel occlusion (2VO), also known as permanent bilateral occlusion of the common carotid arteries, induces chronic cerebral hypoperfusion (CCH) in rats, resulting in neuronal loss and inflammation (particularly in the cortex and hippocampus). The 2VO rat model has been widely used to represent VaD conditions similar to those seen in humans. Synaptic plasticity or long-term potentiation (LTP) is one of the most important neurochemical foundations in learning and memory, deficits of which occur as a result of VaD. The aim of this study is to evaluate the role of cholinergic transmission in LTP impairment of CCH rat model. There is a significant impairment of LTP following the induction of 2VO surgery (p < .05). Treatment with oxotremorine and tacrine cause significant enhancement of LTP and potentiation levels (p < .05). There are also significant effects of paired-pulse facilitations when treated with cholinergic agonists and baseline synaptic transmission with increasing stimulation intensity (p < .0001). AChE activity was only found to increase significantly in the hippocampal region (p < .05). The role of cholinergic neurotransmission has been clearly demonstrated in LTP impairment of the CCH rat model. Augmentation of synaptic transmission was clearly observed in this model via changes of basal synaptic transmission and neurotransmitter release presynaptically.

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Changes in oxidative metabolism and memory and learning in a cerebral hypoperfusion model in rats

Cited by 2 publications

References 34 publications

Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease

Protein arginine methyltransferase 4 modulates nitric oxide synthase uncoupling and cerebral blood flow in Alzheimer's disease

Cholinergic modulation of hippocampal long-term potentiation in chronic cerebral hypoperfused rats

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