[Show abstract][Hide abstract] ABSTRACT: Nitric oxide (NO) has been involved in many pathophysiological brain processes. However, the exact role of NO in the cognitive deficit associated to chronic stress exposure has not been elucidated. In this study, we investigated the participation of hippocampal NO production and their regulation by protein kinase C (PKC) in the memory impairment induced in mice subjected to chronic mild stress model (CMS). CMS mice showed a poor learning performance in both open field and passive avoidance inhibitory task respect to control mice. Histological studies showed a morphological alteration in the hippocampus of CMS mice. On the other hand, chronic stress induced a diminished NO production by neuronal nitric oxide synthase (nNOS) correlated with an increment in gamma and zeta PKC isoenzymes. Partial restoration of nNOS activity was obtained after PKC activity blockade. NO production by inducible nitric oxide synthase isoform was not detected. The magnitude of oxidative stress, evaluated by reactive oxygen species production, after excitotoxic levels of NMDA was increased in hippocampus of CMS mice. Moreover, ROS formation was higher in the presence of nNOS inhibitor in both control and CMS mice. Finally, treatment of mice with nNOS inhibitors results in behavioural alterations similar to those observed in CMS animals. These findings suggest a novel role for nNOS showing protective activity against insults that trigger tissue toxicity leading to memory impairments.
Journal of Neurochemistry 08/2007; 102(1):261-74. DOI:10.1111/j.1471-4159.2007.04528.x · 4.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sensory experience is critical for the formation of neuronal circuits and it is well known that neuronal activity plays a crucial role in the formation and maintenance of synapses. In the vertebrate retina, exposure to different environmental conditions results in structural, physiological, neurochemical and pharmacological changes. Serotoninergic (5HT) amacrine cells of the chicken retina are bistratified interneurons whose primary dendrites descend through the inner nuclear layer (INL) to branch in the inner plexiform layer (IPL) forming two plexi, an outer network, localized to sublamina 1, and an inner network, localized to sublamina 4 and 5 of the IPL. Their development is temporally correlated with the establishment of synapses in the retina and with the emergence of the typical adult electroretinogram. It is unknown, however, which role these cells play in processing visual information and whether visual deprivation modifies their phenotype. Here, we show that, in the chicken, red-light rearing from hatching to postnatal day 12 significantly alters the stratification pattern of 5HT amacrine cells, inhibiting their age-dependent pruning measured with morphometric and densitometric procedures; as well as increasing serotonin immunoreactivity measured as relative optical density. This change in dendritic arborization, accompanied by an increase in serotonin concentration in dark adapted conditions, may decrease visual threshold, thus increasing visual sensitivity.
Developmental Brain Research 01/2006; 160(2):211-8. DOI:10.1016/j.devbrainres.2005.09.007 · 1.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nitric oxide (NO) is a gas involved in neurotransmission in the central nervous system (CNS) and in vertebrate retinas. This paper describes five types of nitrergic neurons in developing and adult chick retina using the nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) reaction. Three of them, nitrergic types 1, 2 and 3, were observed in the inner nuclear layer, while nitrergic type 4 was observed in the ganglion cell layer; nitrergic type 5 were the retinal photoreceptors. Cell processes formed four nitrergic networks, which could be observed in the inner plexiform layer (IPL), at sublayers 1, 3a, 3b and 4. Another nitrergic network was observed in the outer plexiform layer (OPL). From hatching, the dendritic branches were completely developed in the IPL and in the OPL, forming the mentioned networks. Current evidence suggests that NO is coexpressed with other neurotransmitters in neurons of the CNS. Double-staining procedures, using NADPHd and 5HT immunohistochemistry in chicken retina, in a sequential or in an alternative manner, did not reveal the coexistence of these two neurotransmitters in the same neurons, but their networks matched in sublayers 1 and 4 of the IPL.
Developmental Brain Research 04/2000; 120(1):17-25. DOI:10.1016/S0165-3806(99)00166-2 · 1.78 Impact Factor