Effects of obesity induced by high-calorie diet and its treatment with exenatide on muscarinic acetylcholine receptors in rat hippocampus

Silva, Marcelo Florencio Passos; Alves, Patricia Lucio; Alponti, Rafaela Fadoni; Silveira, Paulo Flávio; Abdalla, Fernando Maurício Francis

doi:10.1016/j.bcp.2019.113630

Cited by 7 publications

(13 citation statements)

References 83 publications

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“…Following the results carried out in DIO rats [26], we found that the mAChR1, but not mAChR5, was significantly reduced in the hippocampus of 20-week-old OZRs. Even though downregulation of mAChR3 in the hippocampus of DIO animals has been reported [26], here we did not find any differences either in the hippocampus or in the frontal cortex. Taken together, these results indicate a differential modulation of mAChR1, mAChR3, and mAChR5 subtypes in obese rats compared to that in lean ones.…”

Section: Discussionsupporting

confidence: 62%

Section: Discussionsupporting

confidence: 61%

“…Moreover, a high-calorie diet could be involved in the alterations of the cholinergic system with the modulation of mAChRs [26]. Following the results carried out in DIO rats [26], we found that the mAChR1, but not mAChR5, was significantly reduced in the hippocampus of 20-week-old OZRs. Even though downregulation of mAChR3 in the hippocampus of DIO animals has been reported [26], here we did not find any differences either in the hippocampus or in the frontal cortex.…”

Section: Discussionsupporting

confidence: 61%

“…In addition, galantamine showed anti-inflammatory and beneficial metabolic effects in patients with MetS [25]. The muscarinic acetylcholine receptors (mAChRs) were also found to be strongly influenced by obesity in DIO rats [26].…”

Section: Introductionmentioning

confidence: 99%

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Altered Brain Cholinergic and Synaptic Markers in Obese Zucker Rats

Martinelli

Tomassoni

Roy

et al. 2021

Cells

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The association between obesity and loss of cognitive performance has been recognized. Although there are data regarding the metabolic alterations in obese conditions and the development of neuroinflammation, no clear evidence concerning obesity-related cholinergic and synaptic impairments in the frontal cortex and hippocampus has been reported yet. Here, we investigate different cholinergic and synaptic markers in 12-, 16-, and 20-week-old obese Zucker rats (OZRs) compared with lean littermate rats (LZRs), using immunochemical and immunohistochemical analysis. Consequently, OZRs showed body weight gain, hypertension, and dysmetabolism. In 20-week-old OZRs, the reduction of vesicular acetylcholine transporter (VAChT) and alpha7 nicotinic acetylcholine receptors (α7nAChR) occurred both in the frontal cortex and in the hippocampus, suggesting a cognitive dysfunction due to obesity and aging. Among the muscarinic receptors analyzed, the level of expression of type 1 (mAChR1) was lower in the hippocampus of the older OZRs. Finally, we showed synaptic dysfunctions in OZRs, with a reduction of synaptophysin (SYP) and synaptic vesicle glycoprotein 2B (SV2B) in 20-week-old OZRs, both in the frontal cortex and in the hippocampus. Taken together, our data suggest specific alterations of cholinergic and synaptic markers that can be targeted to prevent cognitive deficits related to obesity and aging.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionsupporting

confidence: 61%

Section: Discussionsupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Altered Brain Cholinergic and Synaptic Markers in Obese Zucker Rats

Martinelli

Tomassoni

Roy

et al. 2021

Cells

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“…Due to its high affinity to muscarinic receptors, the present major role of BZ is in the research of muscarinic receptor distribution, expression and function 6–8 . The binding characteristics of muscarinic receptors were studied using [ 3 H]quinuclidinyl benzilate specific binding analysis 9,10 . Moreover, BZ can be used to induce cognitive impairment in experimental rats to generate a pharmacological model of Alzheimer's disease and other neurodegenerative disorders for testing novel acetylcholinesterase inhibitors 11,12 …”

Section: Introductionmentioning

confidence: 99%

3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats

Dlabková

Herman

Cechova

et al. 2021

Basic Clin Pharma Tox

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3‐Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non‐lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC‐MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half‐life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t1/2 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.

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Why to Study Peptides from Venomous and Poisonous Animals?

Oliveira

Soares

Silva

2023

Int J Pept Res Ther

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Venom and poison peptides are powerful biological weapons and have proven immense pharmacological potential because of their high binding affinity to a wide range of molecular targets. Nonetheless, many of these peptides cannot directly be used as medicines due to their toxicity but their derivatives are very valuable to explore and can be a great treasure trove for the development of novel drugs. This review presents a detailed overview of venom peptides present in reptiles, amphibians, arachnids, gastropods, clitellatas, fish, insects, and mammals. We address the most recent findings that underline their therapeutic potential against a wide variety of diseases from cancer to vascular, autoimmune, and inflammatory diseases. Graphical Abstract

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Effects of obesity induced by high-calorie diet and its treatment with exenatide on muscarinic acetylcholine receptors in rat hippocampus

Cited by 7 publications

References 83 publications

Altered Brain Cholinergic and Synaptic Markers in Obese Zucker Rats

Altered Brain Cholinergic and Synaptic Markers in Obese Zucker Rats

3‐Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats

Why to Study Peptides from Venomous and Poisonous Animals?

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