A critical survey on nitric oxide synthase expression and nitric oxide function in the retinotectal system.

The ongoing research on the roles of the gas nitric oxide (NO) in the nervous system has demonstrated its involvement in neurotransmission, synaptic plasticity, learning, excitotoxicity, neurodegenerative diseases and regulation of the cerebral blood flow. Thus, this molecule has been currently considered an important neuromodulator in CNS. Studies carried out in the visual system, particularly in the retinotectal component, have contributed to this current concept about NO. In the present work, we reviewed critically current data about nitric oxide synthase (NOS) expression in the superior colliculus/optic tectum, as well as the roles of NO in the formation of the retinotopic map and in synaptic plasticity. Several vertebrate species have been used in studies about the NOS expression in the retinotectal system and most of the available results are in agreement with the involvement of NO in the developmental refinement of the retinotectal projections, and its role as a neuromodulator of synaptic function during the processing of visual information. However, the few studies about the functional linkage between NOS expression/NO synthesis and retinotectal topographic refinement/tectal synaptic plasticity are not conclusive and/or sometimes inconsistent, indicating that more experimental data are necessary to improve the understanding about NO functions in this visual subsystem. Predictive models for the involvement of NO as a retrograde messenger in the developmental retinotectal refinement are discussed.

A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse.

Neural stem and progenitor cells are located in the subependyma of the adult forebrain. An increase in adult subependymal cell proliferation is reported after various kinds of brain injury. We demonstrate an expansion of neural precursor cells in the postnatal subependyma in a murine genetic disease model of Huntington's disease (HD), the R6/2 mouse. We used the in vitro neurosphere assay as an index of the number of neural stem cells in vivo and to assess proliferation kinetics in vitro and in vivo bromodeoxyuridine labeling to assess the progenitor cell population and their fates. Disease progression in this model leads to an increase in the numbers of neural stem cells in the adult striatal subependyma. This increase is produced cell non-autonomously by events in the R6/2 brains as the mice become increasingly symptomatic. Once the neural stem cell increase is induced in vivo, it is maintained during in vitro passaging of neural stem cells, but the neural stem cell increase is not reproduced during in vitro passaging of neural stem cells from presymptomatic R6/2 mice. In addition, we show that some of the R6/2 neural progenitor cells show a change from their normal migration destiny toward the olfactory bulb. Instead, some of these cells migrate into the striatum, one of the main affected areas in HD. Our findings demonstrate that HD damage recruits precursor cells in two ways: expansion of neural stem cells and altered migration of progenitor cells.

Nitrergic dendrites in the superficial layers of the rat superior colliculus: retinal afferents and alternatively spliced isoforms in normal and deafferented animals.

The superficial layers of the rat superior colliculus (sSC) receive innervation from the retina and include nitrergic neurons. We have shown previously that in sSC, eye enucleation reduces NADPH diaphorase staining considerably in all but the most proximal dendrites of nitrergic neurons. We have used immunocytochemistry for neuronal nitric oxide synthase (nNOS) at light and electron microscopic levels and bilateral eye enucleation with varied survival times to determine the regulatory changes imposed by the direct and indirect loss of retinal input on apparent nNOS amount and subcellular distribution. In addition, we have used SDS-PAGE and immunoblotting to test alternatively spliced isoforms in normal and deafferented animals. Our results show that unambiguously identified retinal terminals contact nitrergic neurons. In normal dendrites, nNOS immunoreactivity was distributed almost completely within the cytoplasm of the dendrite and along the postsynaptic membrane at synaptic junctions, in association with endoplasmic reticulum, ribosomes and external mitochondrial membranes. In contrast, nNOS labeling was greatly reduced in sSC deprived of retinal projections, and could only be observed in association with mitochondrial membranes and postsynaptic densities. Immunoblots of the soluble fraction from sSC revealed a surprisingly high proportion of the beta isoform with respect to the alpha counterpart in normal colliculi, suggesting an increase in isoform proportion after enucleation, or at least maintenance of the same proportion. It is suggested that ultrastructural alterations observed in sSC cells of enucleated animals may be consequent to plastic reactions of the sSC cells in response to the removal of retinal afferents.

Patters of nitric oxide synthase expression in the developing superior colliculus

Nitric oxide (NO) is synthesized in cells of both the central and peripheral nervous system and has been implicated in several forms of synaptic plasticity. The enzyme that produces NO, nitric oxide synthase (NOS), can be visualized in the brain by the reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry technique (NADPH-d). We have used NADPH-d activity to detect the presence of NOS-positive cells in the developing rat superior colliculus. Our results showed that NOS is present in cells and neuropil in the developing and adult rat superior colliculus. The first NOS-positive cells appeared at postnatal day 7 and were weakly stained. The number and intensity of the NOS-positive cells increased progressively during the following days reaching a maximum at postnatal day 15. By the end of the third postnatal week, both the number and intensity of stained cells showed an adult-like pattern. The NOS-positive cells showed a Golgi-like mosphology and we have found that all cell types present in the superior colliculus express the enzyme. The expression of NOS by tectal cells parallels the functional development of the retino-collicular and cortico-tectal projections and suggest that nitric oxide synthase-positive cells might be involved in this process. In this review we highlighted some of the recent descriptions of the expression of NOS in the mammalian visual system with emphasis in the superior colliculus and correlate these findings with several developmental events taking place in this structure.