Neuroprotective Effects of a Cholecystokinin Analogue in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Parkinson’s Disease Mouse Model

Zhang, Zijuan; Li, Hai; Su, Yunfang; Ma, Junxia; Yuan, Ye; Yu, Ziyang; Shi, Ming; Shao, Simai; Zhang, Zhenqiang; Hölscher, Christian

doi:10.3389/fnins.2022.814430

Cited by 8 publications

(4 citation statements)

References 64 publications

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“…The residence time in the target quadrant and the number of times the mice crossed the platform within 60 s were recorded. In the open field experiment ( Zhang et al, 2022 ), the mice moved freely for 5 min, and the total movement distance and the number of grooming were recorded. In the Y-maze experiment ( Kraeuter et al, 2019 ), the mice were placed at the intersection of three maze arms in turn and moved freely for 5 min.…”

Section: Methodsmentioning

confidence: 99%

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Liu²,

Sun³

et al. 2023

Front. Pharmacol.

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Radix Rehmanniae Praeparata (RRP, Shu Dihuang in Cinese) is widely used as primal medicine in Chinese herbal formula for the treatment of Alzheimer’s disease (AD). However, the underlying mechanism of RRP for AD remains unclear. The aim of this study was to investigate the therapeutic effect of RRP on intracerebroventricular injection of streptozotocin (ICV-STZ)-induced AD model mice and its potential mechanism. ICV-STZ mice were continuously gavaged with RRP for 21 days. The pharmacological effects of RRP were evaluated by behavioral tests, brain tissue H&E staining and hippocampal tau protein phosphorylation levels. The expression levels of insulin receptor (INSR), IRS-1, pSer473-AKT/AKT and pSer9-GSK-3β/GSK-3β proteins in hippocampal and cortical tissues were detected by Western-blot method. The 16S rRNA gene sequencing was used to analyze the changes of intestinal microbiota in mice. The compounds in RRP were analyzed by mass spectrometry and their binding ability to INSR proteins was detected by molecular docking. The results showed that RRP ameliorated cognitive dysfunction and neuronal pathological changes of brain tissue in ICV-STZ mice, reduced tau protein hyperphosphorylation, INSR, IRS-1, pSer473-AKT/AKT, and pSer9-GSK-3β/GSK-3β levels in hippocampal and cortical tissues. Meanwhile, RRP reversed ICV-STZ-induced dysregulation of intestinal microbiota in AD mice. Mass spectrometry analysis showed that the RRP consisted mainly of seven compounds, namely Acteoside (Verbascoside), 5-Hydroxymethyl-2-furaldehyde (5-HMF), Apigenin7-O-glucuronide, Icariin, Gallic acid, Quercetin-3β-D-glucoside, and Geniposide. Molecular docking results further indicated that the compounds in RRP have binding ability to INSR protein and potential multiple synergistic effects. RRP ameliorates cognitive dysfunction and brain histopathological changes in AD mice. The mechanism of RRP ameliorating AD may be related to the regulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota. This study supports the potential anti-AD efficacy of RRP and initially reveals the pharmacological mechanism of RRP, providing a theoretical basis for further clinical application of RRP.

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Section: Methodsmentioning

confidence: 99%

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Liu²,

Sun³

et al. 2023

Front. Pharmacol.

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“…CCK hormone, highly expressed in the hippocampus, has been suggested to enhance healthy mnemonic functions and serves as a biomarker of cognitive and neuronal integrity in neurodegenerative disease (Plagman et al, 2019;Zhang et al, 2022). There have been few studies specifically examining CCK INs, relative to their extensive study in non-pathologic settings, and these are primarily limited to rodent models featuring or exposed to amyloid pathology.…”

Section: Cck Insmentioning

confidence: 99%

Local and long-range GABAergic circuits in hippocampal area CA1 and their link to Alzheimer’s disease

Hernández-Frausto,

Bilash,

Masurkar

et al. 2023

Front. Neural Circuits

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GABAergic inhibitory neurons are the principal source of inhibition in the brain. Traditionally, their role in maintaining the balance of excitation-inhibition has been emphasized. Beyond homeostatic functions, recent circuit mapping and functional manipulation studies have revealed a wide range of specific roles that GABAergic circuits play in dynamically tilting excitation-inhibition coupling across spatio-temporal scales. These span from gating of compartment- and input-specific signaling, gain modulation, shaping input–output functions and synaptic plasticity, to generating signal-to-noise contrast, defining temporal windows for integration and rate codes, as well as organizing neural assemblies, and coordinating inter-regional synchrony. GABAergic circuits are thus instrumental in controlling single-neuron computations and behaviorally-linked network activity. The activity dependent modulation of sensory and mnemonic information processing by GABAergic circuits is pivotal for the formation and maintenance of episodic memories in the hippocampus. Here, we present an overview of the local and long-range GABAergic circuits that modulate the dynamics of excitation-inhibition and disinhibition in the main output area of the hippocampus CA1, which is crucial for episodic memory. Specifically, we link recent findings pertaining to GABAergic neuron molecular markers, electrophysiological properties, and synaptic wiring with their function at the circuit level. Lastly, given that area CA1 is particularly impaired during early stages of Alzheimer’s disease, we emphasize how these GABAergic circuits may contribute to and be involved in the pathophysiology.

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“…Mice were placed in the center of the apparatus. Te number of line crossings and rearing was recorded after 5 min (Smart 3.0, RWD Life Technology, Shenzhen, China), see [41][42][43] for details. Te apparatus was cleaned with 75% alcohol and dried between trials.…”

Section: Open Field Testmentioning

confidence: 99%

A Dual GLP-1/GIP Receptor Agonist Is More Effective than Liraglutide in the A53T Mouse Model of Parkinson’s Disease

Zhang,

Shi,

et al. 2023

Parkinson's Disease

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Parkinson’s disease (PD) is a complex syndrome with many elements, such as chronic inflammation, oxidative stress, mitochondrial dysfunction, loss of dopaminergic neurons, build-up of alpha-synuclein (α-syn) in cells, and energy depletion in neurons, that drive the disease. We and others have shown that treatment with mimetics of the growth factor glucagon-like peptide 1 (GLP-1) can normalize energy utilization, neuronal survival, and dopamine levels and reduce inflammation. Liraglutide is a GLP-1 analogue that recently showed protective effects in phase 2 clinical trials in PD patients and in Alzheimer disease patients. We have developed a novel dual GLP-1/GIP receptor agonist that can cross the blood-brain barrier and showed good protective effects in animal models of PD. Here, we test liraglutide against the dual GLP-1/GIP agonist DA5-CH (KP405) in the A53T tg mouse model of PD which expresses a human-mutated gene of α-synuclein. Drug treatment reduced impairments in three different motor tests, reduced levels of α-syn in the substantia nigra, reduced the inflammation response and proinflammatory cytokine levels in the substantia nigra and striatum, and normalized biomarker levels of autophagy and mitochondrial activities in A53T mice. DA5-CH was superior in almost all parameters measured and therefore may be a better drug treatment for PD than liraglutide.

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Neuroprotective Effects of a Cholecystokinin Analogue in the 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Parkinson’s Disease Mouse Model

Cited by 8 publications

References 64 publications

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Radix Rehmanniae Praeparata (Shu Dihuang) exerts neuroprotective effects on ICV-STZ-induced Alzheimer’s disease mice through modulation of INSR/IRS-1/AKT/GSK-3β signaling pathway and intestinal microbiota

Local and long-range GABAergic circuits in hippocampal area CA1 and their link to Alzheimer’s disease

A Dual GLP-1/GIP Receptor Agonist Is More Effective than Liraglutide in the A53T Mouse Model of Parkinson’s Disease

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