Chlorogenic Acid: a Polyphenol from Coffee Rendered Neuroprotection Against Rotenone-Induced Parkinson’s Disease by GLP-1 Secretion

Sharma, Nishant; Soni, Ritu; Sharma, Monika; Chatterjee, Sayan; Parihar, Nidhi; Mukarram, Mohd; Kale, Ruhi; Sayyed, Adil Ali; Behera, Santosh Kumar; Khairnar, Amit

doi:10.1007/s12035-022-03005-z

Cited by 27 publications

(16 citation statements)

References 61 publications

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“…It is well known that the accumulation of α-syn contributed to the neuropathological degeneration of TH + neurons in SNpc. Next, we performed DAB staining on coronal sections from three levels of SNpc and counted the TH + neurons as per the previously described method 51 . We found a significant decrease in the TH+ neurons in the DSS+Rot group ( p <0.001) compared to control animals.…”

Section: Resultsmentioning

confidence: 99%

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Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more

Sharma

Thakkar

et al. 2022

Preprint

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Background: The contribution of gastrointestinal (GI) inflammation and local exposure to neurotoxins in the gut offers the most in-depth explanation of Parkinson's disease (PD) etiopathogenesis through abnormal accumulation and spreading of alpha-synuclein (α-syn) aggregates from the gut to the brain. Objectives: This study was designed to investigate whether dextran sodium sulfate (DSS)-mediated colitis may have lasting effects on dopaminergic pathways in the brain and whether or not colitis exacerbated susceptibility to later exposure to the neurotoxin rotenone. Methods: To induce chronic colitis, 10 months old C57BL/6 mice were pre-exposed to 3 cycles of 7 days of 1% (w/v) DSS administration in drinking water followed by 14 days of regular drinking water. After colitis-induction, animals received a low dose of intragastric rotenone for the next 8 weeks, followed by testing for Parkinsonian behavior and GI phenotypes of inflammation. At the end of the 8th week after colitis, colon, brain stem, and midbrain tissue were isolated and analyzed for α-syn, inflammatory markers, and dopaminergic neuronal loss. Gut microbial composition was assessed by 16S rRNA sequencing analysis. Results: We found that local rotenone exposure for 8 weeks did not affect colitis severity and colonic tight junction (TJ) protein expression (ZO-1, Occludin, and Claudin-1). On the other hand, we found that while eight weeks of chronic rotenone administration led to an increase in inflammatory markers, the presence of pre-existing colitis resulted in a considerable change in gut microbiota composition and a decrease in TJ's protein expression. In addition, the administration of rotenone in mice post-colitis caused gastrointestinal function impairment and poor behavioral performances. Itworsened rotenone-induced α-syn pathology in the colon, which extended upward and resulted in severe dopaminergic neuron loss and significant astroglia activation in the dorsal motor nucleus of the vagus (DMV), locus coeruleus, substantia nigra as well as in striatum. Interestingly, in the case of rotenone alone, we found that α-syn induced ChAT+ neuronal death is restricted to the DMV. These findings indicate that long-term rotenone exposure in conjunction with early inflammatory intestinal milieu exacerbates the progression of α-syn pathology and aggravates neurodegeneration in the intragastric mouse PD model. Conclusions: This work provides detailed insight into the involvement of GI inflammation triggered after a neurotoxic insult in the colon and explores their potential to impact central dopaminergic degeneration in PD. This way, we can identify potential therapeutic targets that stop the enteric inflammatory processes involved in progressing PD.

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Section: Resultsmentioning

confidence: 99%

“…Images were observed, and photos were taken under a confocal microscope (Leica TCS SP8 Microsystem) as described by Ip et al ., 41,42. Six randomly selected sections over the whole anterior-posterior extent of SNpc were counted, separated by 240 μm (1/6 series).…”

Section: Methodsmentioning

confidence: 99%

Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more

Sharma

Thakkar

et al. 2022

Preprint

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“…The relative amount of miR-126-3p expression was calculated using the comparative Cq method (21). Real time-qPCR for disintegrin and metalloproteinase domain-containing protein 9 (ADAM9), CRK like proto-oncogene, adaptor protein (CRKL), CRK and GAPDH expression were performed using the following primers: ADAM9 forward, 5'-AGA CAG CCG GGG AGTG TTC CTC-3' and reverse, 5'-AGG TGG CCT TGA TGG GAA CTG CT-3'; CRK forward, 5'-AGG GTT ATC CAG AAG CGA GTC-3' and reverse, 5'-CTT CCCA CTG ACC ACT CAC AT-3', CRKL forward, 5'-GTG CTT ATG ACA AGA CTG CCT-3' and reverse, 5'-CAC TCG TTT TCA TCT GGG TTT-3'; collagen-1A1 forward, 5'-CAG GTC TCG GTC ATG GTA CCT-3' and reverse, 5'-GTC GAG GGC CAA GAC GAA-3'; GAPDH forward, 5'-GAG TCA ACG GAT TTG GTC GT-3' and reverse, 5'-TTG ATT TTG GAG GGA TCT CG-3'; 18S forward, 5'-GTA ACC CGT TGA ACC CCA TT-3' and reverse, 5'-CCA TC CAA TCG GTA GTA GCG-3' using SYBR green (22). PCR amplification was performed using the light cycler 96 with pre-incubation at 95˚C for 120 sec, amplification at 40 cycles of 95˚C for 30 sec, 60˚C for 30 sec and 72˚C for 30 sec and then a final extension at 72˚C for 5 min.…”

Section: Droplet Digital Pcr (Ddpcr)mentioning

confidence: 99%

Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment

et al. 2023

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Extracellular vesicles (EVs) and their contents are gaining recognition as important mediators of intercellular communication through the transfer of bioactive molecules, such as non-coding RNA. The present study comprehensively assessed the microRNA (miRNA/miR) content within EVs released from HepG2 liver cancer (LC) cells and LX2 hepatic stellate cells (HSCs) and determined the contribution of EV miRNA to intercellular communication. Using both transwell and spheroid co-cultures of LC cells and HSCs, miR-126-3p within EV was established as a mediator of HSC to LC cell communication that influenced tumor cell migration and invasion, as well as the growth of multicellular LC/HSC spheroids. Manipulation of miR-126-3p either by enforced expression using pre-miR-126-3p or by inhibition using antimiR-126-3p did not alter tumor cell viability, proliferation or sensitivity to either sorafenib or regorafenib. By contrast, enforced expression of miR-126-3p decreased tumor-cell migration. Knockdown of miR-126-3p in tumor cells increased disintegrin and metalloproteinase domain-containing protein 9 (ADAM9) expression and in HSCs increased collagen-1A1 accumulation with an increase in compactness of multicellular spheroids. Within LC/HSC spheroids, ADAM9 and vascular endothelial growth factor expression was increased by silencing of miR-126-3p but diminished with the restoration of miR-126-3p. These studies implicate miR-126-3p in functional effects on migration, invasion and spheroid growth of tumor cells in the presence of HSCs, and thereby demonstrate functional EV-RNA-based intercellular signaling between HSCs and LC cells that is directly relevant to tumor-cell behavior.

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“…Besides incretin functions, GLP1 has been shown to exert anti-inflammatory effects in both the GI tract and central nervous system (CNS) [ 23 , 24 , 25 ]. Moreover, GLP1 possesses neuroprotective effects and triggers neurogenesis [ 26 , 27 , 28 , 29 , 30 , 31 ]. New evidence suggested that GLP1 and glucagon-like peptide 1 receptor (GLP1R), a receptor of GLP1, have protective effects on hypothalamic inflammation and leptin sensitivity in mice [ 25 , 32 ].…”

Section: Enteroendocrine Cell Functions That Might Be Related To Neur...mentioning

confidence: 99%

“…In contrast, a study in a PD mouse model suggested that the oral administration of butyrate could have protective effects on the neurobehavioral impairment via increased EEC activities, such as increased colonic GLP1 expression and brain GLP1R gene expression [ 67 ]. A recent animal study also indicated the neuroprotective effect of GLP1, triggered by chlorogenic acid [ 31 ]. These conflicting characteristics of EECs might be due to the variations in EECs’ homeostasis status or the hormone composition of EECs.…”

Section: Enteroendocrine Cells In Parkinson’s Diseasementioning

confidence: 99%

Involvement of Intestinal Enteroendocrine Cells in Neurological and Psychiatric Disorders

2022

Biomedicines

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Neurological and psychiatric patients have increased dramatically in number in the past few decades. However, effective treatments for these diseases and disorders are limited due to heterogeneous and unclear pathogenic mechanisms. Therefore, further exploration of the biological aspects of the disease, and the identification of novel targets to develop alternative treatment strategies, is urgently required. Systems-level investigations have indicated the potential involvement of the brain–gut axis and intestinal microbiota in the pathogenesis and regulation of neurological and psychiatric disorders. While intestinal microbiota is crucial for maintaining host physiology, some important sensory and regulatory cells in the host should not be overlooked. Intestinal epithelial enteroendocrine cells (EECs) residing in the epithelium throughout intestine are the key regulators orchestrating the communication along the brain-gut-microbiota axis. On one hand, EECs sense changes in luminal microorganisms via microbial metabolites; on the other hand, they communicate with host body systems via neuroendocrine molecules. Therefore, EECs are believed to play important roles in neurological and psychiatric disorders. This review highlights the involvement of EECs and subtype cells, via secretion of endocrine molecules, in the development and regulation of neurological and psychiatric disorders, including Parkinson’s disease (PD), schizophrenia, visceral pain, neuropathic pain, and depression. Moreover, the current paper summarizes the potential mechanism of EECs in contributing to disease pathogenesis. Examination of these mechanisms may inspire and lead to the development of new aspects of treatment strategies for neurological and psychiatric disorders in the future.

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Chlorogenic Acid: a Polyphenol from Coffee Rendered Neuroprotection Against Rotenone-Induced Parkinson’s Disease by GLP-1 Secretion

Cited by 27 publications

References 61 publications

Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more

Intragastric administration of low-dose rotenone post-colitis exacerbates damage to the nigrostriatal dopaminergic system in Parkinson’s disease: The pace accelerates even more

Extracellular vesicle‑mediated miR‑126‑3p transfer contributes to inter‑cellular communication in the liver tumor microenvironment

Involvement of Intestinal Enteroendocrine Cells in Neurological and Psychiatric Disorders

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