Neuroscience
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Different lines of evidence indicate that ATP and nitric oxide (NO) play key roles in mediating neuronal responses after cell damage. Purinergic and nitrergic interactions have been proposed in non neural tissues physiological functions and, in different experimental models of brain injury, both purinergic and nitrergic activations have been reported. The present study was planned to ascertain possible relations of these two systems after brain damage. ⋯ Present data demonstrate that after cerebellar lesion nitrergic and purinergic systems are activated with similar time courses in precerebellar stations. Further, time differences in the relation between nNOS expression and cell survival suggest a multifarious role of NO in mediating cell reaction to axotomy. The tight cellular co-localization and temporal co-activation of purinergic and nitrergic markers indicate possible interactions between these two systems also in the CNS.
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Comparative Study
Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington's disease transgenic mice prior to the onset of motor symptoms.
Inheritance of a single copy of the gene encoding huntingtin (HD) with an expanded polyglutamine-encoding CAG repeat leads to neuronal dysfunction, neurodegeneration and the development of the symptoms of Huntington's disease (HD). We have found that the steady-state mRNA levels of two members of the phosphodiesterase (PDE) multi-gene family decrease over time in the striatum of R6 transgenic HD mice relative to age-matched wild-type littermates. Phosphodiesterase 10A (PDE10A) mRNA and protein levels decline in the striatum of R6/1 and R6/2 HD mice prior to motor symptom development. ⋯ In contrast, PDE4A mRNA levels are relatively low in the striatum and do not differ between age-matched wild-type and transgenic HD mice. This suggests that the regulation of PDE10A and PDE1B, but not PDE4A, mRNA levels is dependent on the relative expression of or number of CAG repeats within the human HD transgene. The loss of phosphodiesterase activity may lead to dysregulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) levels in the striatum, a region of the brain that contributes to the control of movement and cognition.
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Cortical gamma oscillations have been associated with neural processes supporting cognition and the state of consciousness but the effect of general anesthesia on gamma oscillations is controversial. Here we studied the concentration-dependent effect of halothane on gamma (20-60 Hz) power of event-related potentials (ERP) in rat primary visual cortex. ERP to light flashes repeated at 5-s intervals was recorded with chronically implanted, bipolar, intracortical electrodes at selected steady-state halothane concentrations between 0 and 2%. gamma-Band power was calculated for 0-1000, 0-300 and 300-1000 ms poststimulus periods and corresponding prestimulus (PS) periods. ⋯ Single-trial gamma power was present also at 300-1000 ms poststimulus, reflecting ERP not phase-locked to the stimulus. In summary, these observations suggest that (1) gamma activity is present in states ranging from waking to deep halothane anesthesia, (2) halothane does not prevent the transfer of visual input to striate cortex even at surgical plane of anesthesia, and (3) anesthetic-induced loss of consciousness, as reflected by the loss of righting reflex, is not correlated with a reduction in gamma power. Variance with other studies may be due to an underestimation of gamma power by ERP signal averaging as compared with single-trial analysis.
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Peroxisome proliferator-activated and retinoid X receptors (PPARs and RXRs) are transcription factors belonging to the steroid hormone receptor superfamily. Upon activation by their ligands, PPARs and RXRs bind to their target genes as heterodimers. Ligands of these receptors include lipophylic molecules, such as retinoids, fatty acids and eicosanoids, the importance of which in the metabolism and functioning of the nervous tissue is well documented. ⋯ While PPAR beta/delta and RXR beta showed a widespread distribution, alpha and gamma isotypes exhibited a more restricted pattern of expression. The frontal cortex, basal ganglia, reticular formation, some cranial nerve nuclei, deep cerebellar nuclei, and cerebellar Golgi cells appeared rather rich in all studied receptors. Based on our data, we suggest that in the adult CNS, PPARs and RXRs, besides playing roles common to many other tissues, may have specific functions in regulating the expression of genes involved in neurotransmission, and therefore play roles in complex processes, such as aging, neurodegeneration, learning and memory.
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Leptin is a 16 kDa hormone that is produced by adipose tissue and has a central effect on food intake and energy homeostasis. The ability of leptin to cross the blood-brain and blood-cerebrospinal fluid (CSF) barriers and reach or leave the CNS was studied by the bilateral in situ brain perfusion and isolated incubated choroid plexus techniques in the rat. Brain perfusion results indicated that [(125)I]leptin reached the CNS at higher concentrations than the vascular marker, confirming that [(125)I]leptin crossed the brain barriers. ⋯ Studies using the incubated rat choroid plexus model found that [(125)I]leptin could cross the apical membrane of the choroid plexus to leave the CSF. However, this movement was not sensitive to unlabelled human leptin or specific transport inhibitors/modulators (including probenecid, digoxin, deltorphin II, progesterone and indomethacin). This study supports the concept of brain-barrier regulation of leptin distribution to the CNS, and highlights an important link between leptin and the cerebellum.