Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Against Cognitive Decline in Neurodegenerative Diseases

Solés-Tarrés, Irene; Cabezas-Llobet, Núria; Vaudry, David; Xifró, Xavier

doi:10.3389/fncel.2020.00221

Cited by 43 publications

(37 citation statements)

References 173 publications

(255 reference statements)

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“…It is also consistent with the time course of effects of other neuropeptides on intermittent‐access ethanol drinking 42,43 . These relatively acute effects of PACAP may be due to its low metabolic stability 44 ; however, chemical strategies aimed at modifying putative sites of cleavage have identified several PACAP analogs that are more metabolically stable, 45 and these may be useful targets for the development of PACAP‐derived pharmacotherapeutics.…”

Section: Discussionsupporting

confidence: 69%

Effects of pituitary adenylate cyclase‐activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking

et al. 2020

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While limited research has implicated the neuropeptide, pituitary adenylate cyclase‐activating polypeptide (PACAP), in problematic alcohol use, the brain regions and isoforms involved in this effect remain to be determined. One region that has been found both to exhibit PACAP binding and, separately, to be involved in ethanol drinking is the nucleus accumbens (NAc). Thus, this study sought to characterize the effect of the PACAP isoforms in the NAc on ethanol drinking under the intermittent‐access two‐bottle‐choice paradigm, in male and female Long–Evans rats. With microinjection into the medial NAc shell, PACAP‐27 but not PACAP‐38 was found to dose‐dependently reduce binge‐like ethanol drinking. In contrast, the PACAP receptor antagonist, PACAP (6‐27), but not PACAP (6‐38), enhanced ethanol drinking. This effect of PACAP was substance specific, as neither isoform in the NAc shell affected binge‐like sucrose drinking. It was also anatomically specific, as PACAP‐38 rather than PACAP‐27 suppressed ethanol drinking when injected into the NAc core, and PACAP‐27 instead enhanced drinking when injected into the caudal third of the medial NAc shell. Finally, while PACAP‐38 in the NAc shell affected stress‐related exploratory behavior, reducing time spent in the light chamber of a light–dark box, PACAP‐27 did not significantly affect behavior in a light–dark box or open field. Together, these results, showing that PACAP‐27 in the NAc shell attenuates binge‐like ethanol drinking without affecting select stress‐related behaviors, suggest that compounds related to this PACAP isoform should be investigated as potential novel therapeutics for the treatment of alcohol use disorder.

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Section: Discussionsupporting

confidence: 69%

Effects of pituitary adenylate cyclase‐activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking

et al. 2020

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“…PACAP is known for its neuromodulatory and neuroprotective properties [ 16 ]. It is involved in neuronal proliferation and differentiation and axonal growth and development of glial cells [ 16 , 17 , 18 ]. Increased expression of PACAP in the CNS has been noted in disorders caused by neurotoxic agents, such as ethanol [ 29 ], kainic acid [ 30 ], oxidative-related factors [ 31 ], beta-amyloid peptide [ 32 ] and glucotoxicity [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, PACAP is known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection [ 16 ]. Accumulating evidence indicates the anti-apoptotic, anti-inflammatory and antioxidant effects of PACAP in many experimental models of inflammatory and degenerative diseases [ 6 , 13 , 16 , 17 ]. Furthermore, recent studies provide evidence that PACAP has a positive effect on glucose-stimulated insulin secretion and glucose tolerance, stimulates proliferation of beta-cells and may prevent diabetes-related organ complications, such as micro- and macroangiopathy, retinal dysfunction, neuropathy and insufficient insulin secretion [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract

Palus

Bulc

Całka

et al. 2021

IJMS

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Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.

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“…Therefore, it is speculated that the occurrence of cognitive dysfunction in PD patients has a certain relationship with the reduction of PACAP levels. Clinically, although PD has long been known to be characterized by motor disturbances, cognitive dysfunction is also common in patients and is often manifested as dementia, deficits in learning and attention, or impaired executive function among others ( Soles-Tarres et al, 2020 ). This disorder is often mediated by the extracellular or intracellular accumulation of protein aggregates that disrupt synaptic plasticity, leading to neuronal dysfunction and/or neuronal death.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Decreased Serum Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Levels With Non-motor Symptoms in Patients With Parkinson’s Disease

Huang

et al. 2021

Front. Aging Neurosci.

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Objective: Pituitary adenylate-cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuropeptides that exhibit anti-inflammatory and neuroprotective properties, modulating the production of cytokines and chemokines, and the behavior of immune cells. However, the relationship between PACAP and VIP levels and Parkinson’s disease (PD) are not clear. The aim of the current study was to evaluate serum PACAP and VIP levels in PD patients and to analysis the correlation between neuropeptide levels and non-motor symptoms.Methods: In this cross-sectional study, we enrolled 72 patients with idiopathic PD and 71 healthy volunteers. Serum PACAP and VIP levels were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Non-motor symptoms were assessed with the Non-Motor Symptoms Scale (NMSS) for PD, including total and single-item scores.Results: The serum PACAP levels of PD patients were significantly lower than those of healthy controls [(76.02 ± 43.78) pg/ml vs. (154.96 ± 76.54) pg/ml, P < 0.001]; and the serum VIP levels of PD patients were also significantly lower than those of healthy controls [(109.56 ± 15.39) pg/ml vs. (136.46 ± 24.16) pg/ml, P < 0.001]. PACAP levels were inversely correlated only with the score on NMSS item five, assessing Attention/memory (r = −0.276, P < 0.05) and lower serum PACAP levels were detected in the cognitive dysfunction subgroup than in the cognitively intact subgroup [(61.87 ± 32.66) pg/ml vs. (84.51 ± 47.59) pg/ml, P < 0.05]; meanwhile, VIP levels were inversely correlated with the NMSS total score (r = −0.285, P < 0.05) and the single-item scores for item one, assessing Cardiovascular (r = −0.257, P < 0.05) and item three, assessing Mood/cognition (r = −0.373, P < 0.05), and lower serum VIP levels were detected in the anxiety subgroup and depression subgroup than in the non-anxiety subgroup and non-depression subgroup, respectively [(107.45 ± 15.40) pg/ml vs. (116.41 ± 13.67) pg/ml, P < 0.05]; [(104.45 ± 15.26) pg/ml vs. (113.43 ± 14.52) pg/ml, P < 0.05].Conclusion: The serum PACAP and VIP levels of PD patients were significantly lower than those of healthy controls. The non-motor symptoms significantly negatively correlated with serum PACAP level was cognitive dysfunction, while mood disorder was significantly correlated with serum VIP level.

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Protective Effects of Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Against Cognitive Decline in Neurodegenerative Diseases

Cited by 43 publications

References 173 publications

Effects of pituitary adenylate cyclase‐activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking

Effects of pituitary adenylate cyclase‐activating polypeptide isoforms in nucleus accumbens subregions on ethanol drinking

Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract

Correlation of Decreased Serum Pituitary Adenylate Cyclase-Activating Polypeptide and Vasoactive Intestinal Peptide Levels With Non-motor Symptoms in Patients With Parkinson’s Disease

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