Agmatine reverses memory deficits induced by Aβ1–42 peptide in mice: A key role of imidazoline receptors

Kotagale, Nandkishor R.; Dixit, Madhura P.; Garmelwar, Harshal; Bhondekar, Shraddha; Umekar, Milind J.; Taksande, Brijesh G.

doi:10.1016/j.pbb.2020.172976

Cited by 17 publications

(13 citation statements)

References 69 publications

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“…Likewise, agmatine, the proposed endogenous ligand for I 2 receptors, prevented cognitive deficits in amyloid-β 1-42 peptide-injected mice and of note, its effect was augmented and attenuated by I 2 agonists and antagonists, respectively (Kotagale et al, 2020). Collectively, this evidence supports the potential therapeutic effect of I 2 ligands in AD.…”

Section: Introductionsupporting

confidence: 55%

“…Conversely, recently, it was reported that the I 2 ligand BU224 does not ameliorate amyloid‐β amyloidosis in 5XFAD mice but improves memory (Mirzaei et al, 2020). In contrast with LSL60101 like molecules, BU224 blocked the memory‐enhancing effect of agmatine in memory deficits induced by amyloid‐β 42 in mice (Kotagale et al, 2020). These discrepancies between I 2 ligands can be explained by differences in compound administration conditions, such as dose, time (subchronic vs. chronic) and administration route.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence provided by our group demonstrated that selective I 2 ligands protected against cognitive impairment and ameliorated AD pathological features related to amyloid precursor protein processing, tau hyperphosphorylation, neuroinflammation and oxidative stress processes, using well‐established AD animal models (Abás et al, 2017, 2020; Griñán‐Ferré et al, 2019; Vasilopoulou, Griñán‐Ferré, et al, 2020). Likewise, agmatine, the proposed endogenous ligand for I 2 receptors, prevented cognitive deficits in amyloid‐β 1–42 peptide‐injected mice and of note, its effect was augmented and attenuated by I 2 agonists and antagonists, respectively (Kotagale et al, 2020). Collectively, this evidence supports the potential therapeutic effect of I 2 ligands in AD.…”

Section: Introductionmentioning

confidence: 99%

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Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Vasilopoulou

Rodríguez-Arévalo

Bagán

et al. 2021

British J Pharmacology

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Background and Purpose: The development of effective therapeutic strategies against Alzheimer's disease (AD) remains a challenge. I 2 imidazoline receptor ligands have a neuroprotective role in AD. Moreover, co-treatment of AChE inhibitors with neuroprotective agents have shown better effects on the prevention of dementia.Here, we assessed the potential therapeutic effect of the I 2 ligand, donepezil and their combination in 5XFAD mice. Experimental Approach: 5XFAD female mice were treated with low doses (1 mgÁkg À1 Áday À1 ) of LSL60101, donepezil and donepezil plus LSL60101, during 4 weeks per os. Novel object recognition, Morris water maze, open field, elevated plus maze and three-chamber tests were used to evaluate the cognitive and behavioural status after treatment. The effects on AD-like pathology were assessed with immunohistochemistry, western blot, ELISA and qPCR. Key Results: Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour. LSL60101 treatment did not affect anxiety-like behaviour in contrast to donepezil. In the 5XFAD brains, LSL60101 and donepezil/LSL60101 treatments attenuated amyloid-β pathology by decreasing amyloid-β 40 and amyloid-β 42 levels, amyloid-β plaque number and tau hyperphosphorylation. These alterations were accompanied by reduced microglia marker Iba-1 levels and increased Trem2 gene expression. LSL60101 and donepezil decreased glial fibrillary acidic protein (GFAP) astrocytic marker reactivity. However, only LSL60101 and donepezil/LSL60101 treatments significantly increased the synaptic marker levels of post-synaptic density protein 95 and synaptophysin. Conclusion and Implications:Chronic low-dose treatment with selective I 2 -ligands can be an effective treatment for AD and provide insights into combination treatments for symptomatic and disease-modifying drugs.

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Section: Introductionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Vasilopoulou

Rodríguez-Arévalo

Bagán

et al. 2021

British J Pharmacology

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“…Conversely, recently it was reported that the I2-IR ligand BU224 does not ameliorate Aβ amyloidosis in 5XFAD mice (Mirzaei et al, 2020), but improves memory. In contrast with LSL60101 like molecules, BU224 blocked the memory-enhancing effect of agmatine in memory deficits induced by Aβ 1-42 in mice (Kotagale et al, 2020). These discrepancies between I2-IR ligands can be explained by differences in compound administration conditions such as dose, time (sub-chronicvs.…”

Section: Discussionmentioning

confidence: 93%

“…Several lines of evidence provided by our group demonstrated that selective I2-IR ligands protected against cognitive impairment ameliorating AD pathological features related to APP processing, Tau hyperphosphorylation, neuroinflammation and oxidative stress (OS) processes, using well-established AD animal models (Abás et al, 2017;Griñán-Ferré et al, 2019;Abás et al, 2020;Vasilopoulou et al, 2020b). Likewise,agmatine, the proposed endogenous ligand for I2-IR, prevented cognitive deficits in Aβ 1-42 peptide injected mice and of note its effect was augmented and attenuated by I2-IR agonists and antagonists respectively (Kotagale et al, 2020). Collectively, this evidence supports the potential therapeutic effect of I2-IR ligands in AD.…”

Section: Introductionmentioning

confidence: 85%

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model : A Comparative study with donepezil

Vasilopoulou

Rodríguez-Arévalo

Bagán

et al. 2020

Preprint

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Background and Purpose: The development of effective therapeutic strategies against Alzheimer’s disease (AD) remains a challenge. I2 Imidazoline receptors (I2-IR) ligands have a neuroprotective role in AD. While co-treatment of acetylcholinesterase inhibitors with neuroprotective agents have shown better effects on the prevention of dementia. Here, we assessed the potential therapeutic effect of the I2-IR ligand LSL60101, donepezil and their combination in 5XFAD mice. Experimental Approach: 5XFAD female mice were treated with low doses of LSL60101 (1mg/kg/day), donepezil (1mg/kg/day), and donepezil plus LSL60101 (1+1mg/kg/day), during 4 weeks per os. Novel object recognition, Morris water maze, open field, elevated plus maze and three-chamber tests were employed to evaluate the cognitive and behavioural status of the mice after treatment. The effects of the treatments on AD-like pathology were assessed with immunohistochemistry, Western blot and qPCR. Key results: Chronic low-dose treatment with LSL60101 and donepezil reversed cognitive deficits and impaired social behaviour. LSL60101 treatment did not affect anxiety-like behaviour in contrast to donepezil. In the 5XFAD brains, LSL60101 and donepezil/LSL60101 treatments decreased Aβ-pathology and Tau hyperphosphorylation, and these alterations were accompanied by decreased microglia marker Iba-1 levels and increased Trem2 gene expression. LSL60601 and donepezil decreased glial fibrillary acidic protein (GFAP) astrocytic marker reactivity. However, only LSL60601 treatment significantly increased the levels of the synaptic markers post-density 95 (PSD95) and synaptophysin (SYN). Conclusion and implications: Our results suggest that chronic low dose treatment with selective I2-IR ligands can be an effective treatment for AD and provide insights into combination treatments of symptomatic and disease-modifying drugs

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Effects of agmatine on radial‐arm maze memory performance and autistic‐like behaviors in a male rat model of autism

Parvan,

Nozari,

Shabani

et al. 2024

Birth Defects Research

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BackgroundAutism spectrum disorder (ASD) is the fastest‐growing child neuropsychiatric condition. Cognitive dysfunctions such as memory impairments are experienced by patients along with social disturbances and repetitive/stereotypic movements. We have used the radial arm maze (RAM), for measurement of working and reference memory errors in an animal model of autism. In addition, the potential effects of agmatine, an endogenous NMDA antagonist, on RAM performance and autistic‐like behaviors were assessed.MethodsAutism was modeled by valproic acid (VPA) administration at gestational Day 12.5. Autism‐associated behaviors in male offspring were examined in an open field test (OFT) and three‐chambered test (TCT) on postnatal days 50–51. Thereafter, the animals were trained in the RAM (PND 55) until they attained the criteria of 80% correct choices during five consecutive trials. Forty‐eight hours after the acquisition of criteria, agmatine was injected 30 min before subsequent behavioral testing, which included the retention phase of the RAM, OFT, and TCT.ResultsVPA‐treated and intact rats showed the same performance in RAM, and acute injection of agmatine rescued social and anxiety‐like behavior induced by VPA without the effect on RAM.ConclusionIn a rat model of autism, spatial learning, and memory did not change. Agmatine rescued social and anxiety‐like behavior in autistic animals.

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Agmatine reverses memory deficits induced by Aβ1–42 peptide in mice: A key role of imidazoline receptors

Cited by 17 publications

References 69 publications

Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model : A Comparative study with donepezil

Effects of agmatine on radial‐arm maze memory performance and autistic‐like behaviors in a male rat model of autism

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Agmatine reverses memory deficits induced by Aβ1–42 peptide in mice: A key role of imidazoline receptors

Cited by 17 publications

References 69 publications

Disease‐modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease‐modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease-modifying treatment with I2 imidazoline receptor ligand LSL60101 in an Alzheimer’s disease mouse model : A Comparative study with donepezil

Effects of agmatine on radial‐arm maze memory performance and autistic‐like behaviors in a male rat model of autism

Contact Info

Product

Resources

About

Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil

Disease‐modifying treatment with I₂ imidazoline receptor ligand LSL60101 in an Alzheimer's disease mouse model: a comparative study with donepezil