Functional regulation of neuronal nitric oxide synthase expression and activity in the rat retina

Author(s)

Walter, Lais Takata ^[1] ; Vilar Higa, Guilherme Shigueto ^{[2, 1]} ; Schmeltzer, Christian ^[3] ; Sousa, Erica ^[1] ; Kinjo, Erika Reime ^[1] ; Ruediger, Sten ^[3] ; Hamassaki, Dania Emi ^[4] ; Cerchiaro, Giselle ^[5] ; Kihara, Alexandre Hiroaki ^{[2, 1]}

Affiliation

^[1] Univ Fed ABC, Ctr Matemat Computacao & Cognicao, Nucleo Cognicao & Sistemas Complexos, BR-09606070 Sao Bernardo Do Campo, SP - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508 Sao Paulo - Brazil

^[3] Humboldt Univ, Inst Phys, D-10099 Berlin - Germany

^[4] Univ Sao Paulo, Inst Ciencias Biomed, Dept Biol Celular & Desenvolvimento, BR-05508 Sao Paulo - Brazil

^[5] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Nucleo Cognicao & Sistemas Complexos, BR-09606070 Sao Bernardo Do Campo, SP - Brazil

• Document type: Journal article
• Source: Experimental Neurology; v. 261, p. 510-517, NOV 2014.
• Web of Science Citations: 4

Abstract

In the nervous system within physiological conditions, nitric oxide (NO) production depends on the activity of nitric oxide synthases (NOSs). and particularly on the expression of the neuronal isoform (nNOS). In the sensory systems, the role of NO is poorly understood. In this study, we identified nNOS-positive cells in the inner nuclear layer (INL) of the rat retina, with distinct characteristics such as somata size, immunolabeling level and location. Employing mathematical cluster analysis, we determined that nNOS amacrine cells are formed by two distinct populations. We next investigated the molecular identity of these cells, which did not show colocalization with calbindin (CB), choline acetyltransferase (ChAT), parvalbumin (PV) or protein kinase C (PI(C), and only partial colocalization with calretinin (CR), revealing the accumulation of nNOS in specific amacrine cell populations. To access the functional, circuitry-related roles of these cells, we performed experiments after adaptation to different ambient light conditions. After 24 h of dark-adaptation, we detected a subtle, yet statistically significant decrease in nNOS transcript levels, which returned to steady-state levels after 24 h of normal light-dark cycle, revealing that nNOS expression is governed by ambient light conditions. Employing electron paramagnetic resonance (EPR), we demonstrated that dark-adaptation decreases NO production in the retina. Furthermore, nNOS accumulation changed in the dark-adapted retinas, with a general reduction in the inner plexiform layer. Finally, computational analysis based on clustering techniques revealed that dark-adaptation differently affected both types of nNOS-positive amacrine cells. Taken together, our data disclosed functional regulation of nNOS expression and activity, disclosing new circuitry-related roles of nNOS-positive cells. More importantly, this study indicated unsuspected roles for NO in the sensory systems, particularly related to adaptation to ambient demands. (C) 2014 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 08/55210-1 - Cell coupling in the arc of life: development, adaptation and degeneration of the nervous system
• Grantee: Alexandre Hiroaki Kihara
• Support Opportunities: Research Grants - Young Investigators Grants