Neuroscience
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Comparative Study
Hypertension-induced changes in monoamine receptors in the prefrontal cortex of rhesus monkeys.
Hypertension affects approximately 60 million people in the United States. Recent studies have demonstrated that hypertension may produce progressive changes in the CNS. The present study is focused on reports in the literature that hypertension may significantly alter neurotransmitter systems, particularly dopamine (DA) and norepinephrine (NE). ⋯ Eight monkeys underwent surgical coarctation of the mid-thoracic aorta which produced sustained, untreated hypertension as defined by a systolic pressure above 150 mm Hg. Compared with normotensive controls, chronic, untreated hypertension produced a significant decrease in DA1 and NE alpha1 receptor binding and an increase in DA uptake (DAU) receptor binding in the prefrontal cortex. While the mechanisms by which untreated hypertension alters DA and NE receptors is not known, the use of this non-human primate model should provide the means to uncover neurobiological changes that occur with untreated hypertension.
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Comparative Study
Frequency-dependent expression of corticotropin releasing factor in the rat's cerebellum.
Corticotropin releasing factor (CRF), localized in extrinsic afferents in the mammalian cerebellum, is defined as a neuromodulator within cerebellar circuits, and appears to be an essential element in the generation of long term depression, a proposed mechanism for motor learning. These physiological studies are based on exogenous application of CRF and do not address potential mechanisms that may influence endogenous release of the peptide. In the present study, immunohistochemistry was used to analyze changes in the lobular distribution of CRF-like immunoreactivity (LIR). ⋯ Quantitatively, the RIA studies indicate that there is a significant increase in CRF levels in the vermis, hemispheres and flocculus that correlates closely with stimulation frequency. In conclusion, stimulation of cerebellar afferents induces a significant change in the distribution and levels of CRF-LIR in climbing fibers, mossy fibers and glial cells. This suggests that the modulatory effects ascribed to CRF may influence a greater number of target neurons when levels of activity in afferent systems is increased.
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To date, the exact role of inducible nitric oxide synthase (iNOS) in inflammatory pain remains controversial. In the present study, we combined a pharmacological strategy (using a selective iNOS inhibitor) with a genomic strategy (using mice lacking the iNOS gene) to address the function of iNOS in the central mechanism of carrageenan-induced persistent inflammatory pain. In the wild type mice, intrathecal administration of L-N(6)-(1-iminoethyl)-lysine, a selective iNOS inhibitor, significantly inhibited thermal hyperalgesia in the late phase but not in the early phase of carrageenan inflammation. ⋯ We also found that expression of neuronal NOS but not endothelial NOS in the lumbar enlargement segments was significantly increased in iNOS knockout mice compared with wild type mice at 24 h after carrageenan injection. Our results indicate that neuronal NOS might compensate for the function of iNOS in the late phase of carrageenan-induced inflammatory pain in iNOS knockout mice. This suggests that iNOS may be sufficient, but not essential, for the late phase of the carrageenan-induced thermal hyperalgesia.
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To test the hypotheses that (i). electroencephalograms (EEGs) are largely made up of oscillations at many frequencies and (ii). that the peaks in the power spectra represent oscillations, we applied a new method, called the period specific average (PSA) to a wide sample of EEGs. Both hypotheses can be rejected. Although the principal peaks in the two spectra agree most of the time, quite often a peak in the power spectrum accompanies no periodicity peak and some periodicity peaks have no power spectral peak. ⋯ In the face of wide variability, we do not report any systematic differences in periodicity among EEGs from different parts of the brain or different brain states or species; it will take many more exemplars of each state, species or brain part to establish characteristic features. The PSA method may be the best so far proposed to demonstrate and quantify periodicity in wide-band time series with noise, but it has serious limitations. Discussion leads to the conclusion that it is time for a new paradigm or metaphor for brain waves.
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Cisplatin, a commonly used antineoplastic agent, destroys the sensory hair cells in the cochlear and vestibular system leading to irreversible hearing loss and balance problems. Cisplatin-induced hair cell damage presumably occurs by apoptosis. Recent studies suggest that p53 may play an important role initiating cisplatin-induced apoptosis in some cell types. ⋯ Addition of PFT (20-100 microM) to cisplatin-treated cochlear and utricular cultures resulted in a dose-dependent increase in hair cell survival; suppressed the expression of p53 in Western blots and eliminated caspase-1 and caspase-3 labeling in cultures. These results suggest that the tumor suppressor protein, p53, plays a critical role in initiating apoptosis in cochlear and vestibular hair cells. Temporary suppression of p53 with PFT provides significant protection against cisplatin-induced hair cell loss and offers the potential for reducing the ototoxic, vestibulotoxic and neurotoxic side effects of cisplatin.