Losartan improved hippocampal long‐term potentiation impairment induced by repeated LPS injection in rats

Hosseini, Mahmoud; Salmani, Hossein; Baghcheghi, Yousef

doi:10.14814/phy2.14874

Cited by 14 publications

(4 citation statements)

References 50 publications

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“…Furthermore, preliminary evidence indicates that ARBs may counteract episodic memory aberrations often seen in PTSD ( 16 , 17 ) because ARBs have increased memory performance and prevented cognitive decline in elderly humans ( 18 , 19 ). Similar effects have been shown in rodents ( 13 , 20 , 21 ), where ARBs further enhanced hippocampal long-term potentiation ( 22 ), the core cellular mechanism in learning and memory ( 23 ). Notably, patients with PTSD perform more poorly than healthy control participants and trauma-exposed individuals on episodic memory tasks ( 16 ) that involve neutral ( 17 , 24 , 25 ) and emotional material ( 26 ), as well as autobiographical events ( 27 ).…”

supporting

confidence: 67%

Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals

Shkreli,

Thoroddsen,

Kobelt

et al. 2024

Biological Psychiatry Global Open Science

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supporting

confidence: 67%

Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals

Shkreli,

Thoroddsen,

Kobelt

et al. 2024

Biological Psychiatry Global Open Science

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“…77 Given that successful performance in both the SA and IA tasks requires an intact hippocampus, 39,[78][79][80][81][82] our findings suggest that HF impairs hippocampal function, and that Losartan improves memory in HF rats via an effect on this brain region. This interpretation is supported by findings showing that systemic administration of Losartan reverses deficits in hippocampal synaptic plasticity 75,83 and that systemic doses of Losartan that have no effect in control animals prevented LPS-induced hippocampal-dependent memory impairments, including IA retention deficits. 84 Together, these findings support exacerbated Ang II-AT1aR signaling in the hippocampus as a pivotal mechanism driving neuroinflammation and cognitive impairment after myocardial infarction.…”

Section: Ang Ii-at1r Signaling Contributes To Hippocampal Neuroinflam...mentioning

confidence: 72%

Angiotensin II–Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats

et al. 2023

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Background: Heart failure (HF) is a debilitating disease affecting >64 million people worldwide. In addition to impaired cardiovascular performance and associated systemic complications, most patients with HF suffer from depression and substantial cognitive decline. Although neuroinflammation and brain hypoperfusion occur in humans and rodents with HF, the underlying neuronal substrates, mechanisms, and their relative contribution to cognitive deficits in HF remains unknown. Methods: To address this critical gap in our knowledge, we used a well-established HF rat model that mimics clinical outcomes observed in the human population, along with a multidisciplinary approach combining behavioral, electrophysiological, neuroanatomical, molecular and systemic physiological approaches. Results: Our studies support neuroinflammation, hypoperfusion/hypoxia, and neuronal deficits in the hippocampus of HF rats, which correlated with the progression and severity of the disease. An increased expression of AT1aRs (Ang [angiotensin] II receptor type 1a) in hippocampal microglia preceded the onset of neuroinflammation. Importantly, blockade of AT1Rs with a clinically used therapeutic drug (Losartan), and delivered in a clinically relevant manner, efficiently reversed neuroinflammatory end points (but not hypoxia ones), resulting in turn in improved cognitive performance in HF rats. Finally, we show than circulating Ang II can leak and access the hippocampal parenchyma in HF rats, constituting a possible source of Ang II initiating the neuroinflammatory signaling cascade in HF. Conclusions: In this study, we identified a neuronal substrate (hippocampus), a mechanism (Ang II–driven neuroinflammation) and a potential neuroprotective therapeutic target (AT1aRs) for the treatment of cognitive deficits in HF.

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“…For example, 24 hours following a single exposure to 1 mg/kg LPS, young adult Balb/c mice had reduced synaptopodin-mRNA expression, and impaired LTP induction in CA1 hippocampal neurons 72 . In a continuous LPS administration model, male Wistar rats showed reduced monosynaptic field excitatory postsynaptic potentials in CA1 neurons three days post-LPS injection battery (0.25 mg/kg/day for six consecutive days) 73 . To our knowledge, we are the first to examine synaptic communication consequences of repeated, intermittent exposure to LPS.…”

Section: Discussionmentioning

confidence: 99%

Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice

Engler-Chiurazzi

Russel

Povroznik

et al. 2022

Preprint

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Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections is emerging as a potential driver of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with a subtle but significantly accelerated trajectory of cognitive decline. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia.

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Losartan improved hippocampal long‐term potentiation impairment induced by repeated LPS injection in rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 50 publications

Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals

Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals

Angiotensin II–Mediated Neuroinflammation in the Hippocampus Contributes to Neuronal Deficits and Cognitive Impairment in Heart Failure Rats

Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice

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