Neuroscience
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Recent research suggests an involvement of pro-opiomelanocortin (POMC) gene products (e.g., beta-endorphin) in modulating cocaine-induced reward and addiction-like behaviors in rodents. In this study, we investigated whether chronic "binge" cocaine and its withdrawal altered POMC gene expression in the brain of rats. Male Fischer rats were treated with two different chronic (14-day) "binge" pattern cocaine administration regimens (three injections at 1-h intervals, i.p.): steady-dose (45mg/kg/day) and escalating-dose (90mg/kg on the last day). ⋯ In contrast, after acute (1-day) withdrawal from chronic "binge" escalating-dose regimen, but not steady-dose regimen, there were increased hypothalamic POMC mRNA levels that persisted into 14days of protracted withdrawal. To study the role of the endogenous opioid systems in the cocaine withdrawal effects, we administered a single naloxone injection (1mg/kg) that caused elevated POMC mRNA levels observed 24h later in cocaine naïve rats, but it did not lead to further increases in cocaine-withdrawn rats. Our results suggest that during withdrawal from chronic "binge" escalating-dose cocaine: (1) there was a persistent increase in hypothalamic POMC gene expression; and (2) hyposensitivity of the POMC gene expression to naloxone indicates altered opioidergic tone at or above the hypothalamic level.
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At tripartite synapses, astrocytes undergo calcium signaling in response to release of neurotransmitters and this calcium signaling has been proposed to play a critical role in neuron-glia interaction. Recent work has now firmly established that, in addition, neuronal activity also evokes sodium transients in astrocytes, which can be local or global depending on the number of activated synapses and the duration of activity. Furthermore, astrocyte sodium signals can be transmitted to adjacent cells through gap junctions and following release of gliotransmitters. ⋯ Furthermore, recovery from sodium transients through Na(+)/K(+)-ATPase requires a measurable amount of ATP, resulting in an activation of glial metabolism. In this review, we present basic principles of sodium regulation and the current state of knowledge concerning the occurrence and properties of activity-related sodium transients in astrocytes. We then discuss different aspects of the relationship between sodium changes in astrocytes and neuro-metabolic coupling, putting forward the idea that indeed sodium might serve as a new type of intracellular ion signal playing an important role in neuron-glia interaction and neuro-metabolic coupling in the healthy and diseased brain.
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The same clock-genes, including Period (PER) 1 and 2, that show rhythmic expression in the suprachiasmatic nucleus (SCN) are also rhythmically expressed in other brain regions that serve as extra-SCN oscillators. Outside the hypothalamus, the phase of these extra-SCN oscillators appears to be reversed when diurnal and nocturnal mammals are compared. Based on mRNA data, PER1 protein is expected to peak in the late night in the paraventricular nucleus of the hypothalamus (PVN) of nocturnal laboratory rats, but comparable data are not available for a diurnal species. ⋯ All three groups showed elevated levels of melatonin at night, with higher levels during both the day and night being associated with the levels of activity displayed by each group. The differential phase of rhythms in the clock-gene protein in the PVN of diurnal and nocturnal animals presents a possible mechanism for explaining species differences in the phase of autonomic rhythms controlled, in part, by the PVN. The present study suggests that the phase of the oscillator of the PVN does not determine that of the melatonin rhythm in diurnal and nocturnal species or in diurnal and nocturnal chronotypes within a species.
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Monge's disease, also known as chronic mountain sickness (CMS), is a disease that potentially threatens more than 140 million highlanders during extended time living at high altitudes (over 2500m). The prevalence of CMS in Andeans is about 15-20%, suggesting that the majority of highlanders (non-CMS) are rather healthy at high altitudes; however, CMS subjects experience severe hypoxemia, erythrocytosis and many neurologic manifestations including migraine, headache, mental fatigue, confusion, and memory loss. The underlying mechanisms of CMS neuropathology are not well understood and no ideal treatment is available to prevent or cure CMS, except for phlebotomy. ⋯ We discovered that CMS neurons were much less excitable (higher rheobase) than non-CMS neurons. This decreased excitability was not caused by differences in passive neuronal properties, but instead by a significantly lowered Na(+) channel current density and by a shift of the voltage-conductance curve in the depolarization direction. Our findings provide, for the first time, evidence of a neuronal abnormality in CMS subjects as compared to non-CMS subjects, hoping that such studies can pave the way to a better understanding of the neuropathology in CMS.
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A fundamental problem in neurophysiology is the understanding of neuronal mechanisms by which the central nervous system produces a sequence of voluntary or involuntary motor acts from a diverse repertory of movements. These kinds of transitions between motor acts are extremely complex; however, they could be analyzed in a more simple form in decerebrate animals in the context of spinal central pattern generation. ⋯ Because no changes in phase of these neurons from scratching to post-scratching locomotion were found, we suggest that in the lumbar spinal cord there are neurons associated with both motor tasks. Moreover, because of its high reproducibility we suggest that the study of post-scratching fictive locomotion, together with the unitary recording of neurons, could become a useful tool to study neuronal mechanisms underlying transitions from one rhythmic motor task to another, and to study in more detail the central pattern generator circuitry in the spinal cord.