Neuroscience
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Comparative Study
Ultra-low dose naltrexone potentiates the anticonvulsant effect of low dose morphine on clonic seizures.
Significant potentiation of analgesic effects of opioids can be achieved through selective blockade of their stimulatory effects on intracellular signaling pathways by ultra-low doses of opioid receptor antagonists. However, the generality and specificity of this interaction is not well understood. The bimodal modulation of pentylenetetrazole-induced seizure threshold by opioids provide a model to assess the potential usefulness of this approach in seizure disorders and to examine the differential mechanisms involved in opioid anti- (morphine at 0.5-3 mg/kg) versus pro-convulsant (20-100 mg/kg) effects. ⋯ However, ultra-low dose naltrexone could not increase the maximal anticonvulsant effect of morphine (1-3 mg/kg), possibly due to a ceiling effect. The proconvulsant effects of morphine on seizure threshold were minimally altered by ultra-low doses of naltrexone while being completely blocked by a higher dose (1 mg/kg) of the antagonist. The present data suggest that ultra-low doses of opioid receptor antagonists may provide a potent strategy to modulate seizure susceptibility, especially in conjunction with very low doses of opioids.
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Comparative Study
Expression of axon guidance molecules and their related genes during development and sexual differentiation of the olfactory bulb in rats.
Axon guidance molecules and related proteins such as semaphorin 3A, neuropilin-1, plexin-1, netrin-1, growth-associated protein, olfactory marker protein, cypin and collapsin response mediator proteins guide the development of neural circuits in the olfactory bulb. In this study, transcriptions of these genes were examined in the olfactory bulb of female, male and neonatal testosterone propionate-treated female rats at the ages of 2, 5, 10, 15, 20, 25, 30 and 45 days. The semaphorin 3A, neuropilin-1, growth-associated protein and collapsin response mediator protein 1-5 genes were expressed significantly higher during the early development stages than in adulthood while the opposite is true for the olfactory marker protein. ⋯ A late effect of the neonatal testosterone propionate treatment on netrin-1, growth-associated protein, olfactory marker protein, collapsin response mediator proteins 1, 3, 4 and cypin gene expression was observed. The expression profiles of collapsin response mediator proteins and their related genes in the developing olfactory bulb confirmed most studies on the relationship between collapsin response mediator proteins and development in the brain. Sex differences of semaphorin 3A, neuropilin-1 as well as collapsin response mediator protein 3 at the early development stage and the late effect of neonatal testosterone propionate treatment on the expressions of netrin-1, growth-associated marker protein, cypin and collapsin response mediator proteins 1, 3 and 5 genes may indicate a possible role of these molecules on sexual differentiation of the olfactory bulb.
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Infant mammals cycle rapidly between sleep and wakefulness and only gradually does a more consolidated sleep pattern develop. The neural substrates responsible for this consolidation are unknown. To establish a reliable measure of sleep-wake cyclicity in infant rats, nuchal muscle tone was measured in 2-, 5-, and 8-day-old rats, as were motor behaviors associated with sleep (i.e. myoclonic twitching) and wakefulness (e.g. kicking, stretching). ⋯ The temporal coherence of atonia and myoclonic twitching was not disrupted by any of the manipulations. These results suggest the presence of a bistable mesopontine circuit governing rapid sleep-wake cycling that does not include the LC and that comes increasingly under hypothalamic control during the first postnatal week. This circuit may represent a basic building block with which other sleep components become integrated during ontogeny.
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We investigated the CNS delivery of insulin-like growth factor-I (IGF-I), a 7.65 kDa protein neurotrophic factor, following intranasal administration and the possible pathways and mechanisms underlying transport from the nasal passages to the CNS. Anesthetized adult male Sprague-Dawley rats were given [125I]-IGF-I intranasally or intravenously and then killed by perfusion-fixation within 30 min. Other animals were killed following cisternal puncture and withdrawal of cerebrospinal fluid (CSF) or intranasal administration of unlabeled IGF-I or vehicle. ⋯ Intravenous [125I]-IGF-I resulted in blood and peripheral tissue exposure similar to that seen following intranasal administration but CNS concentrations were significantly lower. Finally, delivery of IGF-I into the CNS activated IGF-I signaling pathways, confirming some portion of the IGF-I that reached CNS target sites was functionally intact. The results suggest intranasally delivered IGF-I can bypass the blood-brain barrier via olfactory- and trigeminal-associated extracellular pathways to rapidly elicit biological effects at multiple sites within the brain and spinal cord.
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Astrocytes are highly complex cells that respond to a variety of external stimulations. One of the chief functions of astrocytes is to optimize the interstitial space for synaptic transmission by tight control of water and ionic homeostasis. Several lines of work have, over the past decade, expanded the role of astrocytes and it is now clear that astrocytes are active participants in the tri-partite synapse and modulate synaptic activity in hippocampus, cortex, and hypothalamus. ⋯ In conjuncture, the brain appears to have a distinct astrocytic perivascular system, involving several potassium channels as well as aquaporin 4, a membrane water channel, which has been localized to astrocytic endfeet and mediate water fluxes within the brain. The multitask functions of astrocytes are essential for higher brain function. One of the major challenges for future studies is to link receptor-mediated signaling events in astrocytes to their roles in metabolism, ion, and water homeostasis.