Daily Cycling Of Nitric Oxide Synthase (nos) In The Hippocampus Of Pigeons (c. Livia)

Background: Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results: Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. 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The absence of maternal pineal melatonin rhythm during pregnancy and lactation impairs offspring physical growth, neurodevelopment, and behavior

Maternal melatonin provides photoperiodic information to the fetus and thus influences the regulation and timing of the offspring's internal rhythms and preparation for extra-uterine development. There is clinical evidence that melatonin deprivation of both mother and fetus during pregnancy, and of the neonate during lactation, results in negative long-term health outcomes. As a consequence, we hypothesized that the absence of maternal pineal melatonin might determine abnormal brain programming in the offspring, which would lead to long-lasting implications for behavior and brain function. To test our hypothesis, we investigated in rats the effects of maternal melatonin deprivation during gestation and lactation (MMD) to the offspring and the effects of its therapeutic replacement. The parameters evaluated were: (1) somatic, physical growth and neurobehavioral development of pups of both sexes; (2) hippocampal-dependent spatial learning and memory of the male offspring; (3) adult hippocampal neurogenesis of the male offspring. Our findings show that MMD significantly delayed male offspring's onset of fur development, pinna detachment, eyes opening, eruption of superior incisor teeth, testis descent and the time of maturation of palmar grasp, righting reflex, free-fall righting and walking. Conversely, female offspring neurodevelopment was not affected. Later on, male offspring show that MMD was able to disrupt both spatial reference and working memory in the Morris Water Maze paradigm and these deficits correlate with changes in the number of proliferative cells in the hippocampus. Importantly, all the observed impairments were reversed by maternal melatonin replacement therapy. In summary, we demonstrate that MMD delays the appearance of physical features, neurodevelopment and cognition in the male offspring, and points to putative public health implications for night shift working mothers