AI Article Synopsis
- The study investigates how injecting NMDA into rats affects neuroprotective factors in the retina, focusing on BDNF, PACAP-38, VIP, and ADNP.
- NMDA injection led to a significant decrease in VIP levels while BDNF increased initially, indicating a complex neuroprotective response.
- Results suggest that maintaining these neuroprotective mechanisms could be critical for developing therapies for retinal degeneration.
Article Abstract
Purpose: To evaluate the effect of intravitreal injection of N-methyl-D-aspartate (NMDA) on brain-derived neurotrophic factor (BDNF), pituitary adenylate cyclase-activating peptide-38 (PACAP-38), vasoactive intestinal peptide (VIP) and the VIP-associated glial protein activity-dependent neuroprotective protein (ADNP) in the rat retina. These elements have well-documented neuroprotective properties and may thus be integrated in endogenous neuroprotective mechanisms in the retina which break down in NMDA excitotoxicity.
Methods: A volume of 2 μl of 100 nmol NMDA was intravitreally injected into one eye of rats, the untreated eye served as a control. Time-dependent effects of NMDA on VIP, PACAP-38 and BDNF were detected by radioimmunoassay and ELISA, and the effect on the expression of VIP, PACAP-38 and ADNP was evaluated by quantitative RT-PCR 20 days after NMDA injection. Topical flunarizine served to find out whether the effect of NMDA is counteracted.
Results: Compared to PACAP-38, VIP levels significantly decreased on days 1, 7, 14, 28 and 56 after NMDA injection indicating that VIPergic cells are more vulnerable than PACAP-38-expressing cells. The expression of VIP and ADNP but not of PACAP-38 was found to be reduced, and application of topical flunarizine counteracted the decrease of VIP. BDNF levels significantly increased after days 1 and 3.
Conclusion: The early upregulation of BDNF seems to act neuroprotectively and leads to a delay of ganglion cell loss. Although there is no direct evidence, the decrease of VIP and ADNP - the consequence of the presence of NMDA receptors on these peptide-expressing cells - might contribute to the breakdown of endogenous neuroprotective mechanisms given that the decrease of the VIP-related ADNP runs in parallel with the decrease of VIP. Activating and maintaining these mechanisms must be the primary aim in the therapy of diseases with retinal neuronal degeneration.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/j.1755-3768.2009.01828.x | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Estrogens impair hypophagia and hypothalamic cell activation induced by vasoactive intestinal peptide, but not by pituitary adenylate cyclase-activating polypeptide.
Peptides
November 2024
Programa Multicêntrico de Pós-Graduação em Ciências Fisiológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil; Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil; Laboratório de Fisiologia Neuroendócrina e Metabolismo, Departamento de Ciências Fisiológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil. Electronic address:
Article Synopsis
- The study investigated how estradiol affects food intake and receptor expression in postmenopausal rats, particularly looking at the neuropeptides VIP and PACAP in specific hypothalamic areas.
- Results showed that estradiol reduced the expression of the VPAC2 receptor and disrupted the hypophagic (appetite-reducing) effects of VIP, while PACAP continued to suppress food intake.
- Additionally, estradiol altered plasma glucose and free fatty acid levels in these rats, suggesting different mechanisms in how VIP and PACAP influence energy homeostasis in the context of estrogen loss.
Intranasal administration of recombinant human BDNF as a potential therapy for some primary headaches.
J Headache Pain
October 2024
Dompé Farmaceutici SpA, Via Santa Lucia 6, 20122, Milano, Italy.
Article Synopsis
- BDNF plays an important role in brain function and may help with pain and depression; this study tested its effectiveness against migraines using an animal model.
- Researchers administered two doses of recombinant human BDNF (rhBDNF) to rats with pain induced by NTG injections, measuring pain response and changes in brain-related neuropeptides and cytokine levels.
- Results showed that rhBDNF significantly reduced migraine-related pain and altered gene expression similarly to the migraine medication sumatriptan, indicating its potential as a non-invasive migraine treatment.
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.
Int J Mol Sci
August 2024
School of Molecular Bioscience, University of Sydney, Sydney, NSW 2006, Australia.
Inflammation with expression of interleukin 6 (IL-6) in the central nervous system (CNS) occurs in several neurodegenerative/neuroinflammatory conditions and may cause neurochemical changes to endogenous neuroprotective systems. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are two neuropeptides with well-established protective and anti-inflammatory properties. Yet, whether PACAP and VIP levels are altered in mice with CNS-restricted, astrocyte-targeted production of IL-6 (GFAP-IL6) remains unknown.
View Article and Find Full Text PDFDifferential Expression of PACAP/VIP Receptors in the Post-Mortem CNS White Matter of Multiple Sclerosis Donors.
Int J Mol Sci
August 2024
Laboratory of Cellular & Molecular Neuroscience (LCMN), School of Life Sciences, Faculty of Science, University of Technology Sydney, P.O. Box 123, Sydney, NSW 2007, Australia.
Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing-remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls.
View Article and Find Full Text PDFProbing PAC1 receptor activation across species with an engineered sensor.
Elife
August 2024
Institute of Pharmacology and Toxicology, University of Zürich, Zurich, Switzerland.
Class-B1 G-protein-coupled receptors (GPCRs) are an important family of clinically relevant drug targets that remain difficult to investigate via high-throughput screening and in animal models. Here, we engineered PAClight1, a novel genetically encoded sensor based on a class-B1 GPCR (the human PAC1 receptor, hmPAC1R) endowed with high dynamic range (Δ/ = 1100%), excellent ligand selectivity, and rapid activation kinetics ( = 1.15 s).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!