ArticleMolecular neurobiology2018
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Enhances Hippocampal Synaptic Plasticity and Improves Memory Performance in Huntington's Disease.
Article in Molecular neurobiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- More Than Three Decades After Discovery of the Neuroprotective Effect of PACAP, What Is Still Preventing Its Clinical Use?Journal of molecular neuroscience : MN · 2025Review
- mGluR5 in Pyramidal Neurons in the Hippocampus Mediates Chronic Stress-Induced Memory Deficits.CNS neuroscience & therapeutics · 2025Article
- Age-Dependent Regulation of Hippocampal Inflammation by the Mitochondrial Translocator Protein in Mice.Aging cell · 2025Article
- Increased Expression of the Neuropeptides PACAP/VIP in the Brain of Mice with CNS Targeted Production of IL-6 Is Mediated in Part by Trans-Signalling.International journal of molecular sciences · 2024Article
- The Potential of the Nose-to-Brain Delivery of PACAP for the Treatment of Neuronal Disease.Pharmaceutics · 2023Review
- PACAP6-38 improves nitroglycerin-induced central sensitization by modulating synaptic plasticity at the trigeminal nucleus caudalis in a male rat model of chronic migraine.The journal of headache and pain · 2023Article
- Novel Small Molecule Positive Allosteric Modulator SPAM1 Triggers the Nuclear Translocation of PAC1-R to Exert Neuroprotective Effects through Neuron-Restrictive Silencer Factor.International journal of molecular sciences · 2022Article
- The neuropeptide PACAP alleviates T. gondii infection-induced neuroinflammation and neuronal impairment.Journal of neuroinflammation · 2022Article
- Review
- Nose-to-Brain Delivery of Therapeutic Peptides as Nasal Aerosols.Pharmaceutics · 2022Review
- Therapeutic Strategies in Huntington's Disease: From Genetic Defect to Gene Therapy.Biomedicines · 2022Review
- Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases.Biomedicines · 2022Review
- Pituitary Adenylate Cyclase-Activating Polypeptide Protects Against Cognitive Impairment Caused by Chronic Cerebral Hypoperfusion.Molecular neurobiology · 2021Article
- New Avenues for the Treatment of Huntington's Disease.International journal of molecular sciences · 2021Review
- Stability Test of PACAP in Eye Drops.Journal of molecular neuroscience : MN · 2021Article
- Generation of KS-133 as a Novel Bicyclic Peptide with a Potent and Selective VIPR2 Antagonist Activity that Counteracts Cognitive Decline in a Mouse Model of Psychiatric Disorders.Frontiers in pharmacology · 2021Article
- Editorial: Novel Therapeutic Potential for Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP), Vasoactive Intestinal Peptide (VIP) and Related Peptides in Cognition Deficits.Frontiers in cellular neuroscience · 2021Article
- Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Protects Striatal Cells and Improves Motor Function in Huntington's Disease Models: Role of PAC1 Receptor.Frontiers in pharmacology · 2021Article
- Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke.Aging and disease · 2020Review
- Intranasal Delivery: Effects on the Neuroimmune Axes and Treatment of Neuroinflammation.Pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Deficits in hippocampal synaptic plasticity result in cognitive impairment in Huntington's disease (HD). Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts neuroprotective actions, mainly through the PAC1 receptor. However, the role of PACAP in cognition is poorly understood, and no data exists in the context of Huntington's disease (HD). Here, we investigated the ability of PACAP receptor stimulation to enhance memory development in HD. First, we observed a hippocampal decline of all three PACAP receptor expressions, i.e., PAC1, VPAC1, and VPAC2, in two different HD mouse models, R6/1 and HdhQ7/Q111, from the onset of cognitive dysfunction. In hippocampal post-mortem human samples, we found a specific decrease of PAC1, without changes in VPAC1 and VPAC2 receptors. To determine whether activation of PACAP receptors could contribute to improve memory performance, we conducted daily intranasal administration of PACAP38 to R6/1 mice at the onset of cognitive impairment for seven days. We found that PACAP treatment rescued PAC1 level in R6/1 mice, promoted expression of the hippocampal brain-derived neurotrophic factor, and reduced the formation of mutant huntingtin aggregates. Furthermore, PACAP administration counteracted R6/1 mice memory deficits as analyzed by the novel object recognition test and the T-maze spontaneous alternation task. Importantly, the effect of PACAP on cognitive performance was associated with an increase of VGlut-1 and PSD95 immunolabeling in hippocampus of R6/1 mice. Taken together, these results suggest that PACAP, acting through stimulation of PAC1 receptor, may have a therapeutic potential to counteract cognitive deficits induced in HD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.