Brain research
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Clinical observations suggest that depressed patients were less sensitive to experimental pain than healthy subjects. However, few animal studies are reported concerning the association of depression and pain. The purpose of this study was to investigate the effects of unpredictable chronic mild stress (UCMS) induced depression on the perceived intensity of painful stimulation in rats. ⋯ The results showed that rats exposed to UCMS exhibited significantly higher thermal and mechanical pain thresholds in comparison to the non-depressed controls. In particular, the PWT of the SNL group was restored to nearly normal level after three weeks of UCMS, and even comparable to that of the control group. These results strongly suggest that the depressed subjects have decreased sensitivity to externally applied noxious stimulation, which is consistent with our previous findings.
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Structural sexual dimorphism and asymmetry in human cerebellum have been described in previous research, but results remain inconclusive or even conflicting. In this study, gender differences and hemispheric asymmetries in global and regional human cerebellum gray matter (GM) were estimated in an age-matched sample (n=112) of young Chinese adults. An optimized voxel-based morphometry (VBM) in spatial unbiased infratentorial template (SUIT) space together with an automated atlas-based volumetric approach were performed for mapping regional gray matter (GM) gender-related differences across the entire cerebellum. ⋯ Gender differences in males showed higher leftward asymmetry sparsely within a few lobules and lower rightward asymmetry mainly within lobule Crus II, as compared with females. The acquired detailed morphologic knowledge of normal human cerebellum could establish a baseline for comparison with pathologic changes in the cerebellum. Moreover, our results might help to address controversies in thestudy of sexual dimorphisms and asymmetric patterns in human cerebellum.
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The balance between descending inhibition and facilitation is thought to be disturbed in chronic pain states. Increased facilitation by spinally released serotonin has been suggested by demonstration that mechanically evoked neuronal responses of wide dynamic range neurons are inhibited by 5-HT3 receptor antagonists in rats following spinal nerve ligation (SNL) but not sham operation. Despite these physiologic data, the effects of spinal 5-HT3 receptor blockade on behavioral hypersensitivity and neurochemical alterations in spinal serotonergic system have not been thoroughly investigated following spinal nerve ligation in the rat. ⋯ These results do not support anatomic plasticity of descending serotonergic pathways or tonic 5-HT3 receptor activity in maintaining hypersensitivity after nerve injury and in contrast to previous studies fail to demonstrate an anti-hypersensitivity effect of intrathecal injection of the 5-HT3 receptor antagonist ondansetron. Importantly, behavioral measures of mechanical hypersensitivity assess threshold responses whereas physiological studies of mechanically evoked neuronal responses involve application of suprathreshold stimuli. Thus, suprathreshold or more intense stimuli may be necessary to recruit descending serotonergic facilitatory drive required to observe the inhibitory effects of ondansetron on spinal neuronal excitability and behavioral hypersensitivity.
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Phytanic acid (Phyt) tissue concentrations are increased in Refsum disease and other peroxisomal disorders characterized by neurologic damage and brain abnormalities. The present work investigated the in vitro effects of Phyt, at concentrations found in these peroxisomal disorders, on important parameters of energy metabolism in brain cortex of young rats. The parameters analyzed were CO(2) production from labeled acetate and glucose, the activities of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase, as well as of the respiratory chain complexes I-IV, creatine kinase and Na(+),K(+)-ATPase. ⋯ Membrane synaptical Na(+),K(+)-ATPase activity was also reduced by Phyt, with no alteration of creatine kinase activity. Considering the importance of the electron flow through the respiratory chain for brain energy metabolism (oxidative phosphorylation) and of Na(+),K(+)-ATPase activity for maintaining membrane potential necessary for neurotransmission, the data indicate that Phyt impairs brain bioenergetics at the level of energy formation, as well as neurotransmission. It is presumed that Phyt-induced impairment of these important systems may be involved at least in part in the neurological damage found in patients affected by disorders in which brain Phyt concentrations are increased.
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Administration of non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists (e.g. phencyclidine, MK-801) has been shown to elicit behavioral abnormalities related to symptoms of schizophrenia, such as spontaneous locomotor activity and impaired sensorimotor gating, as represented by deficits of prepulse inhibition (PPI). We sought to determine whether transient blockade of NMDA receptors at the neonatal stage would produce dopamine supersensitivity around puberty, as manifested by these behavioral measures. ⋯ MK-801 administration also disrupted PPI without affecting startle amplitudes around puberty. These findings suggest that transient exposure to MK-801 in the neonatal stage causes exaggerated dopamine transmission and cognitive deficits, particularly in the post-puberty stage.