Neuroscience
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Most functional imaging studies of memory retrieval investigate memory for standardized laboratory stimuli. However, naturally acquired autobiographical memories differ from memories of standardized stimuli in important ways. Neuroimaging studies of natural memories may reveal distinctive patterns of brain activation and may have particular value in assessing clinical disorders of memory. ⋯ The posterior cingulate cortex has strong reciprocal connections with entorhinal and parahippocampal cortices. Studies of early Alzheimer's disease, temporal lobectomy, and hypoxic amnesia show that hypometabolism of the posterior cingulate cortex is an early and prominent indicator of pathology in these patients. Our findings suggest that autobiographical memory retrieval tasks could be used to probe the functional status of the posterior cingulate cortex in patients with early Alzheimer's disease or at risk for that condition.
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We have addressed the molecular mechanism(s) of hyperalgesia, which depends on increased excitability of dorsal horn neurons and on sensitization of primary afferent nociceptors, during peripheral inflammation. Following unilateral adjuvant-induced inflammation in the rat hind paw, time-course changes in behavioral hyperalgesia and functional activities of Ca2+/phospholipid-dependent protein kinase C isozymes were examined. Inflammation was characterized by increase in paw diameter, and behavioral hyperalgesia was quantified as paw withdrawal latency from a radiant heat source. ⋯ Quantitative immunohistochemical analyses demonstrated intensified protein kinase CbetaII-like immunoreactivity on the side of the spinal cord ipsilateral to the inflammation. Time-course for increases in the activity of membrane-associated protein kinase CbetaII, and in intensity of protein kinase CbetaII-immunoreactivity, paralleled inflammation-mediated changes in paw withdrawal latency and paw diameter. Our findings indicate an apparent involvement of protein kinase CbetaII isozyme specifically in the molecular mechanism(s) of thermal hyperalgesia.
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Na(+)-independent K(+)-Cl(-) cotransporters function in the regulation of cell volume, control of CNS excitability and epithelial ion transport. Several K(+)-Cl(-) cotransporter isoforms are expressed in the nervous system, and KCC3 in particular is expressed at significant levels in both the brain and spinal cord. The cellular localization of this transporter has, however, not been determined. ⋯ Brain sections also showed white matter enhancement, but also cellular signal consistent with pyramidal neurons and Purkinje cells. The base of the choroid plexus epithelium was also strongly labeled. These data demonstrate the specificity and diversity of KCC3 expression in the mouse CNS.
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Cation-chloride cotransporters have been considered to play pivotal roles in controlling intracellular and extracellular ionic environments of neurons and hence controlling neuronal function. We investigated the total distributions of K-Cl cotransporter 1 (KCC1), KCC2 (KCC2), and Na-K-2Cl cotransporter 1 (NKCC1) messenger RNAs in the adult rat nervous system using in situ hybridization histochemistry. KCC2 messenger RNA was abundantly expressed in most neurons throughout the nervous system. ⋯ The expression levels of KCC1 and NKCC1 messenger RNAs were relatively low, however, positive neurons were observed in several regions, including the olfactory bulb, hippocampus, and in the granular layer of the cerebellum. In addition, positive signals were seen in the non-neuronal cells, such as choroid plexus epithelial cells, glial cells, and ependymal cells, suggesting that KCC1 and NKCC1 messenger RNAs were widely expressed in both neuronal and non-neuronal cells in the nervous system. These results clearly indicate a wide area- and cell-specific variation of cation chloride cotransporters, emphasizing the central role of anionic homeostasis in neuronal function and communication.
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Comparative Study
Orphanin FQ produces gender-specific modulation of trigeminal nociception: behavioral and electrophysiological observations.
The present study aimed to determine if orphanin FQ, an endogenous ligand for the opioid receptor like-1 receptor, produces gender-specific effects in the modulation of N-methyl-D-aspartate (NMDA)-evoked responses of trigeminal nociceptive neurons, and in the NMDA-induced nociceptive behavior. Single-unit extracellular recordings were made from nociceptive-specific and wide dynamic range neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized (1.5 g/kg urethane) rats. In the proestrous female, orphanin FQ applied microiontophoretically produced facilitation of the NMDA-evoked responses in 50% (16/32) of nociceptive neurons, inhibition in 31% (10/32), and biphasic effects in 19% (6/32). ⋯ In contrast, in estradiol-treated ovariectomized animals, orphanin FQ facilitated the NMDA-induced scratching behavior by 210%. We conclude from these studies that orphanin FQ is primarily pronociceptive in the female and primarily antinociceptive in the male. Furthermore, we suggest that estrogen is involved in generating the gender-specific effects of orphanin FQ.