Sitagliptin and Liraglutide Modulate L-dopa Effect and Attenuate Dyskinetic Movements in Rotenone-Lesioned Rats

Badawi, Ghada A.; Fattah, Mai A. Abd El; Zaki, Hala F.; Sayed, Moushira I. El

doi:10.1007/s12640-019-9998-3

Cited by 34 publications

(11 citation statements)

References 88 publications

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“…The histopathological scoring of H&E stained sections were evaluated as follows: 0, none; 1–2, mild; 3, moderate; 4, severe. Then the mean number of scoring in each group was calculated separately and compared among different groups 54,55 …”

Section: Methodsmentioning

confidence: 99%

Pentoxifylline prevents epileptic seizure via modulating HMGB1/RAGE/TLR4 signalling pathway and improves memory in pentylenetetrazol kindling rats

Badawi

Shokr

Zaki

et al. 2021

Clin Exp Pharma Physio

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Epilepsy is a chronic widely prevalent neurologic disorder, affecting brain functions with a broad spectrum of deleterious consequences. High mobility group box1 (HMGB1) is a nuclear non‐histone protein that targets vital cell receptor of toll‐like receptor 4 (TLR4) and advanced glycation end products (RAGE). HMGB1 mediated TLR4/RAGE cascade has been scored as a key culprit in neuroinflammatory signalling that critically evokes development of impaired cognition and epilepsy. The current study aimed to investigate the neuroprotective effect of pentoxifylline (PTX) on pentylenetetrazol (PTZ)‐kindling rats by its anti‐inflammatory/antioxidant capacity and its impact on memory and cognition were investigated, too. PTZ was intraperitoneally injected 35 mg/kg, every 48 h, for 14 doses, to evoke kindling model. Phenytoin (30 mg/kg, i.p.) and PTX (60 mg/kg, i.p.) or their combination were given once daily for 27 days. PTX treatment showed a statistically significant effect on behavioural, histopathological and neurochemical analysis. PTX protected the PTZ kindling rats from epileptic seizures and improved memory and cognitive impairment through the Morris water maze (MWM) test. Furthermore, PTX reversed PTZ hippocampal neuronal loss by decreasing protein expression of amyloid‐β peptide (Aβ), Tau and β site‐amyloid precursor protein cleavage enzyme 1 (BACE1), associated with a marked reduction in expression of inflammatory mediators such as HMGB1, TL4, and RAGE proteins. Furthermore, PTX inhibited hippocampal apoptotic caspase 1 protein, total reactive oxygen species (TROS) along with upregulated erythroid 2‐related factor 2 (Nrf2) content. In conclusion, PTX or its combination with phenytoin represent a promising drug to inhibit the epilepsy progression via targeting the HMGB1/TLR4/RAGE signalling pathway.

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Section: Methodsmentioning

confidence: 99%

Pentoxifylline prevents epileptic seizure via modulating HMGB1/RAGE/TLR4 signalling pathway and improves memory in pentylenetetrazol kindling rats

Badawi

Shokr

Zaki

et al. 2021

Clin Exp Pharma Physio

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“…In rotenone-induced PD model, liraglutide together with sitagliptin, a DPP IV inhibitor, increased striatal DA and tyrosine hydroxylase protein levels, reduced neuroinflammation, and reversed neuronal loss (Badawi et al, 2017). Liraglutide was also able to attenuate dyskinesia, a serious complication of long-term therapy with L -dopa (Badawi et al, 2019).…”

Section: Glp-1ras As Neuroprotective Agents In Neurodegenerative Disementioning

confidence: 99%

Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases

et al. 2019

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Diabetes mellitus is one of the major risk factors for cognitive dysfunction. The pathogenesis of brain impairment caused by chronic hyperglycemia is complex and includes mitochondrial dysfunction, neuroinflammation, neurotransmitters’ alteration, and vascular disease, which lead to cognitive impairment, neurodegeneration, loss of synaptic plasticity, brain aging, and dementia. Glucagon-like peptide-1 (GLP-1), a gut released hormone, is attracting attention as a possible link between metabolic and brain impairment. Several studies have shown the influence of GPL-1 on neuronal functions such as thermogenesis, blood pressure control, neurogenesis, neurodegeneration, retinal repair, and energy homeostasis. Moreover, modulation of GLP-1 activity can influence amyloid β peptide aggregation in Alzheimer’s disease (AD) and dopamine (DA) levels in Parkinson’s disease (PD). GLP-1 receptor agonists (GLP-1RAs) showed beneficial actions on brain ischemia in animal models, such as the reduction of cerebral infarct area and the improvement of neurological deficit, acting mainly through inhibition of oxidative stress, inflammation, and apoptosis. They might also exert a beneficial effect on the cognitive impairment induced by diabetes or obesity improving learning and memory by modulating synaptic plasticity. Moreover, GLP-1RAs reduced hippocampal neurodegeneration. Besides this, there are growing evidences on neuroprotective effects of these agonists in animal models of neurodegenerative diseases, regardless of diabetes. In PD animal models, GPL-1RAs were able to protect motor activity and dopaminergic neurons whereas in AD models, they seemed to improve nearly all neuropathological features and cognitive functions. Although further clinical studies of GPL-1RAs in humans are needed, they seem to be a promising therapy for diabetes-associated cognitive decline.

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“…These rodent models of LID vastly increase accessibility for more researchers to investigate this troublesome side effect of L-DOPA and, like their NHP counterparts, have been validated in that their LIDs may be reversed by amantadine [ 176 , 177 ]. Albeit less-well studied, rotenone-treated rats have also been shown to develop LIDs [ 178 , 179 ] so would be worth considering in future dyskinesia research studies.…”

Section: Modelling L-dopa-induced Dyskinesiamentioning

confidence: 99%

Animal models of Parkinson’s disease: a guide to selecting the optimal model for your research

et al. 2021

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Parkinson’s disease (PD) is a complex, multisystem disorder characterised by alpha synuclein pathology, degeneration of nigrostriatal dopaminergic neurons, multifactorial pathogenetic mechanisms and expression of a plethora of motor and non-motor symptoms. Animal models of PD have already been instructive in helping us unravel some of these aspects. However, much remains to be discovered, requiring continued interrogation by the research community. In contrast to the situation for many neurological disorders, PD benefits from of a wide range of available animal models (pharmacological, toxin, genetic and alpha-synuclein) but this makes selection of the optimal one for a given study difficult. This is especially so when a study demands a model that displays a specific combination of features. While many excellent reviews of animal models already exist, this review takes a different approach with the intention of more readily informing this decision-making process. We have considered each feature of PD in turn - aetiology, pathology, pathogenesis, motor dysfunctions and non-motor symptoms - highlighting those animal models that replicate each. By compiling easily accessible tables and figures, we aim to provide the reader with a simple, go-to resource for selecting the optimal animal model of PD to suit their research needs.

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Sitagliptin and Liraglutide Modulate L-dopa Effect and Attenuate Dyskinetic Movements in Rotenone-Lesioned Rats

Cited by 34 publications

References 88 publications

Pentoxifylline prevents epileptic seizure via modulating HMGB1/RAGE/TLR4 signalling pathway and improves memory in pentylenetetrazol kindling rats

Pentoxifylline prevents epileptic seizure via modulating HMGB1/RAGE/TLR4 signalling pathway and improves memory in pentylenetetrazol kindling rats

Glucagon-Like Peptide-1: A Focus on Neurodegenerative Diseases

Animal models of Parkinson’s disease: a guide to selecting the optimal model for your research

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