The aim of this study is to describe the postnatal change in dendritic morphology of those motoneurons in the hypoglossal nucleus that innervate the genioglossus muscle. Forty genioglossal (GG) motoneurons from four age groups (1-2, 5-6, 13-15, and 19-30 postnatal days) were labeled by intracellular injection of neurobiotin in an in vitro slice preparation of the rat brainstem and were reconstructed in three-dimensional space. The number of primary dendrites per GG motoneuron was approximately 6 and remained unchanged with age. The development of these motoneurons from birth to 13-15 days was characterized by a simplification of the dendritic tree involving a decrease in the number of terminal endings and dendritic branches. Motoneurons lost their 6th-8th order branches, in parallel with an elongation of their terminal dendritic branches maintaining the same combined dendritic length. The elongation of terminal branches was attributed to both longitudinal growth and the apparent lengthening caused by resorption of distal branches. The elimination of dendritic branches tended to increase the symmetry of the tree, as revealed by topological analysis. Later, between 13-15 days and 19-30 days, there was a reelaboration of the dendritic arborization returning to a configuration similar to that found in the newborn. The length of terminal branches was shorter at 19-30 days, while the length of preterminal branches did not change, suggesting that the proliferation of branches at 19-30 days takes place in the intermediate parts of terminal branches. The three-dimensional distribution of dendrites was analyzed by dividing space into six equal volumes (hexants). This analysis revealed that GG motoneurons have major components of their dendritic tree oriented in the lateral, medial, and dorsal hexants. Further two-dimensional polar analysis (consisting of eight sectors) revealed a reconfiguration of the tree from birth up to 5-6 days involving resorption of dendrites in the dorsal, dorsomedial, and medial sectors and growth in the lateral sector. Later in development (between 13-15 days and 19-30 days), there was growth in all sectors, but of a greater magnitude in the dorsomedial, medial, and dorsolateral sectors.

This study describes the postnatal change in size of motoneurons in the hypoglossal nucleus that innervate the genioglossus muscle. Such anatomical information is essential for determining the cellular mechanisms responsible for the changes observed in the electrical properties of these motoneurons during postnatal development. The cells analyzed here are part of an earlier study (Núñez-Abades et al. [1994] J. Comp. Neurol. 339:401-420) where 40 genioglossal (GG) motoneurons from four age groups (1-2, 5-6, 13-15, and 19-30 postnatal days) were labeled by intracellular injection of neurobiotin in an in vitro slice preparation of the rat brainstem and their cellular morphology was reconstructed in three-dimensional space. The sequence of postnatal dendritic growth can be described in two phases. The first phase, between birth (1-2 days) and 13-15 days, was characterized by no change in either dendritic diameter (any branch order) or dendritic surface area of GG motoneurons. However, maturation of the dendritic tree produced more surface area at greater distances from the soma by redistributing existing membrane (retracting some terminal branches). During the second phase, between 13-15 days and 19-30 days, the dendritic surface area doubled as a result of an increase in the dendritic diameter across all branch orders and a generation of new terminal branches. In contrast to the growth exhibited by the dendrites, there was little discernible postnatal growth of somata. At all ages, dendrites of GG motoneurons show the largest amount of tapering in the first-and second-order dendrites. The calculated dendritic trunk parameter deviated from a value 1.0, indicating that the dendritic tree of developing GG motoneurons cannot be modeled accurately as an equivalent cylinder. However, the value of this parameter increased with age. Strong correlations were found between the diameter of the first-order dendrite and the dendritic surface area, dendritic volume, combined dendritic length, and, to a lesser extent, the number of terminal dendrites in GG motoneurons. Correlations were also found between somal and dendritic geometry but only when data were pooled across all age groups. These data support earlier studies on kitten phrenic motoneurons, which concluded that postnatal growth of motoneurons was not a continuous process. Based on the fact that there was no growth in the first 2 weeks, the changes in the membrane properties described during this phase of postnatal development (e.g., decrease in input resistance) cannot be attributed to increases in the total membrane surface area of these motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Melatonin is an indolamine synthesized and secreted by the pineal gland along with other extrapineal sources including immune system cells, the brain, skin and the gastrointestinal tract. Growing interest in this compound as a potential therapeutic agent in several diseases stems from its pleiotropic effects. Thus, melatonin plays a key role in various physiological activities that include regulation of circadian rhythms, immune responses, the oxidative process, apoptosis or mitochondrial homeostasis. Most of these processes are altered during inflammatory pathologies, among which neurodegenerative and bowel diseases stand out. Therapeutic assays with melatonin indicate that it has a beneficial therapeutic value in the treatment of several inflammatory diseases, such as Alzheimer, Amiotrophic Lateral, Multiple Sclerosis and Huntigton´s disease as well as ulcerative colitis. However, contradictory effects have been demonstrated in Parkinson´s and Chron´s diseases, which, in some cases, the reported effects were beneficial while in others the pathology was exacerbated. These various results may be related to several factors. In the first place, it should be taken into account that at the beginning of the inflammation phase there is a production of reactive oxygen species (ROS) that should not be blocked by exclusively antioxidant molecules, since, on the one hand, it would be interfering with the action of neutrophils and macrophages and, on the other, with the apoptotic signals activated by ROS. It is also important to keep in mind that the end result of an anti-inflammatory molecule will depend on the degree of inflammation or whether or not it has been resolved and has therefore become chronic. In this review we present the use of melatonin in the control of inflammation underlying the above mentioned diseases. These actions are mediated through their receptors but also with their direct antioxidant action and melatonin's ability to break the vicious cycle of ROSinflammation. This review is aimed at evaluating the effect of melatonin on activity of the inflammatory process and at its immunomodulator effects.

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1. Experiments were performed to determine the change in membrane properties of genioglossal (GG) motoneurons during development. Intracellular recordings were made in 127 GG motoneurons from rats postnatal ages 1-30 days. 2. The input resistance (R(in)) and the membrane time constant (t(aum)) decreased between 5-6 and 13-15 days from 84.8 +/- 25.4 (SD) to 47.0 +/- 18.9 M omega (P < 0.01) and from 10.0 +/- 4.2 to 7.3 +/- 3.3 ms (P < 0.05), respectively. During this period, the rheobase (Irh) increased (P < 0.01) from 0.13 +/- 0.07 to 0.27 +/- 0.14 nA, and the percentage of cells exhibiting inward rectification increased from 5 to 40%. Voltage threshold (Vthr) of the action potential remained unchanged postnatally. 3. There was also a postnatal change in the shape of the action potential. Specifically, between 1-2 and 5-6 days, there was a decrease (P < 0.05) in the spike half-width from 2.23 +/- 0.53 to 1.45 +/- 0.44 ms, resulting, in part, from a steepening (P < 0.05) of the slope of the falling phase of the action potential from 21.6 +/- 10.1 to 32.9 +/- 13.1 mV/ms. The slope of the rising phase also increased significantly (P < 0.01) between 1-2 and 13-15 days from 68.4 +/- 31.0 to 91.4 +/- 44.3 mV/ms. 4. The average duration of the medium afterhyperpolarization (mAHPdur) decreased (P < 0.05) between 1-2 (193 +/- 53 ms) and 5-6 days (159 +/- 43 ms). Whereas the mAHPdur was found to be independent of membrane potential, there was a linear relationship between the membrane potential and the amplitude of the medium AHP (mAHPamp). From this latter relationship, a reversal potential for the mAHPamp was extrapolated to be -87 mV. No evidence for the existence of a slow AHP was found in these developing motoneurons. 5. All cells analyzed (n = 74) displayed adaptation during the first three spikes. The subsequent firing pattern was classified into two groups, adapting and nonadapting. Cells at birth were all adapting, whereas all cells but two from animals 13 days and older were nonadapting. At the intermediate age (5-6 days), the minority (27%) was adapting and the majority (73%) was nonadapting. 6. The mean slope of primary range for the first interspike interval (1st ISI) was approximately 90 Hz/nA. This value was similar for both adapting and nonadapting cells and did not change postnatally.(ABSTRACT TRUNCATED AT 400 WORDS)

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Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.