Blockade of arachidonic acid pathway induces sprouting in the adult but not in the neonatal uncrossed retinotectal projection

• Published in: Neuroscience Vol. 139; no. 3; pp. 979 - 989
• Main Authors: Campello-Costa, P., Fosse-Júnior, A.M., Oliveira-Silva, P., Serfaty, C.A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 2006; Elsevier
• Subjects: Animals; Animals, Newborn; Arachidonic Acid - metabolism; arachidonic acid pathway; Biological and medical sciences; critical period; Enzyme Inhibitors - pharmacology; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Indomethacin - pharmacology; lesion-induced plasticity; Lipoxygenase Inhibitors; Masoprocol - pharmacology; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Phospholipases A - antagonists & inhibitors; Phospholipases A2; Prostaglandin-Endoperoxide Synthases - pharmacology; Quinacrine - pharmacology; Rats; Retina - injuries; retrograde messenger; Signal Transduction - drug effects; Signal Transduction - physiology; Synapses - drug effects; Synapses - metabolism; Synaptic Transmission - drug effects; Synaptic Transmission - physiology; topographical map; Vertebrates: nervous system and sense organs; Visual Pathways - drug effects; Visual Pathways - growth & development; Visual Pathways - metabolism; visual system; AA; retrograde messenger; 20-HETE; topographical map; critical period; HRP; PND; visual system; NDGA; arachidonic acid pathway; lesion-induced plasticity; SO; PLA 2; SGS; Polyunsaturated fatty acid; Lipids; Projection; Arachidonic acid; Visual system; n-6 fatty acid; Plasticity; Unsaturated fatty acid; Lesion; Critical period
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2005.12.039

The uncrossed retinotectal projection of rats undergoes extensive axonal elimination and subsequent growth of axonal arbors in topographically appropriate territories within the first two/three postnatal weeks. Nitric oxide has been implicated in development and stabilization of synapses in the retinotectal pathway since blockade of nitric oxide synthesis disrupts the normal pattern of retinal innervation in subcortical nuclei. The present work investigated the role of arachidonic acid pathway in the development and maintenance of ipsilateral retinotectal axons. We also investigated the role of this retrograde messenger in the modulation of plasticity that follows retinal lesions in the opposite eye. Pigmented rats received systemic treatment with quinacrine, a phospholipase A
2 inhibitor, indomethacin, a cyclooxygenase inhibitor, nordihydroguaiaretic acid, a 5-lipoxygenase inhibitor or vehicle during 4–8 days at various postnatal ages. Rats given a unilateral temporal retinal lesion were treated with either quinacrine or vehicle during the same period. For anterograde tracing of ipsilateral retinal projections, animals received intraocular injections of horseradish peroxidase. Before the third postnatal week no difference was observed in the laminar or topographic organization of the ipsilateral retinotectal projection between vehicle and treated rats in either normal or lesion conditions. After the third postnatal week, however, systemic blockade of phospholipase A
2 or 5-lipoxygenase, but not cyclooxygenase induced sprouting of uncrossed axons throughout the collicular visual layers in unoperated rats. In retinal lesion groups, phospholipase A
2 blockade increased the sprouting of uncrossed intact axons to the collicular surface in the same period. The results suggest that arachidonic acid or lipoxygenase metabolites play a role in the maintenance of the retinotectal synapses after the critical period and that the blockade of the arachidonic acid pathway induces reactive sprouting of retinal axons late in development.