The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders.novelty ͉ prefrontal cortex ͉ amygdala ͉ cingulate gyrus T he prefrontal cortex (PFC) is a heterogeneous brain region whose expansion in primates contributes to increased flexibility and control of cognition and comportment. Whether the PFC is divided into domain-specific regions has come under close scrutiny. A traditional approach to this question has involved contrasting spatial versus object processing to determine whether the PFC is organized along a dorsal-ventral axis analogous to posterior visual neocortex (1). However, electrophysiological studies in monkeys (2, 3) and neuroimaging studies in humans (4-7) have produced conflicting evidence for such a functional parcellation.An alternative organization of PFC has been proposed in recent neuroanatomical models. Mayberg (8) postulated that ventral regions of PFC are specialized for ''vegetative-somatic'' functions, whereas dorsal regions are specialized for ''attentional-cognitive'' functions. This model further posits that the rostral anterior cingulate gyrus acts as an interface between the two processing streams. Mood disorders are hypothesized to reflect failure of coordinated interaction among these PFC compartments. Other anatomical models support the distinction between a dorsal attentional control system and a ventral emotional arousal system that relay information from posterior parietal cortex and amygdala into dorsal and ventral sectors of the PFC, respectively (9, 10).In the present study, functional MRI (fMRI) was used to test whether attentional and emotional functions are compartmentalized into distinct prefrontal systems in the human brain. An attention-demanding target detection task (''visual oddball'' paradigm) was modified from our previous studies in wh...

No abstract

Docosahexaenoic acid (C22:6, n-3), a major n-3 fatty acid of the brain, has been implicated in restoration and enhancement of memory-related functions. Because Alzheimer's disease impairs memory, and infusion of amyloid-b (Ab) peptide (1-40) into the rat cerebral ventricle reduces learning ability, we investigated the effect of dietary pre-administration of docosahexaenoic acid on avoidance learning ability in Ab peptide-produced Alzheimer's disease model rats. After a mini-osmotic pump filled with Ab peptide or vehicle was implanted in docosahexaenoic acid-fed and control rats, they were subjected to an active avoidance task in a shuttle avoidance system apparatus. Pre-administration of docosahexaenoic acid had a profoundly beneficial effect on the decline in avoidance learning ability in the Alzheimer's disease model rats, associated with an increase in the cortico-hippocampal docosahexaenoic acid/arachidonic acid molar ratio, and a decrease in neuronal apoptotic products. Docosahexaenoic acid pre-administration furthermore increased cortico-hippocampal reduced glutathione levels and glutathione reductase activity, and suppressed the increase in lipid peroxide and reactive oxygen species levels in the cerebral cortex and hippocampus of the Alzheimer's disease model rats, suggesting an increase in antioxidative defence. Docosahexaenoic acid is thus a possible prophylactic means for preventing the learning deficiencies of Alzheimer's disease.

In gene therapy to treat cancer, typically only a fraction of the tumor cells can be successfully transfected with a gene. However, in the case of brain tumor therapy with the thymidine kinase gene from herpes simplex virus (HSVtk), not only the cells transfected with the gene but also neighboring others can be killed in the presence ofganciclovir. (Cx43), were used, not only tk+ cells, but also tkcells were killed, presumably due to the transfer, via Cx43-mediated GJIC, of toxic ganciclovir molecules phosphorylated by HSV-tk to the tk-cells. Such bystander effect was not observed when tk+ and tk-cells were cocultured without direct cell-cell contact between those two types of cells. Thus, our results give strong evidence that the bystander effect seen in HSV-tk gene therapy may be due to Cx-mediated GJIC.

No abstract

Gap junction (GJ) channels are formed by two hemichannels (connexons), each contributed by the cells taking part in this direct cell-cell communication conduit. Hemichannels that do not interact with their counterparts on neighboring cells feature as a release pathway for small paracrine messengers such as nucleotides, glutamate, and prostaglandins. Connexins are phosphorylated by various kinases, and we compared the effect of various kinase-activating stimuli on GJ channels and hemichannels. Using peptides identical to a short connexin (Cx) amino acid sequence to specifically block hemichannels, we found that protein kinase C, Src, and lysophosphatidic acid (LPA) inhibited GJs and hemichannel-mediated ATP release in Cx43-expressing C6 glioma cells (C6-Cx43). Lipopolysaccharide (LPS) and basic fibroblast growth factor (bFGF) inhibited GJs, but they stimulated ATP release via hemichannels in C6-Cx43. LPS and bFGF inhibited hemichannel-mediated ATP release in HeLa-Cx43 cells, but they stimulated it in HeLa-Cx43 with a truncated carboxy-terminal (CT) domain or in HeLa-Cx26, which has a very short CT. Hemichannel potentiation by LPS was inhibited by blockers of the arachidonic acid metabolism, and arachidonic acid had a potentiating effect like LPS and bFGF. We conclude that GJ channels and hemichannels display similar or oppositely directed responses to modulatory influences, depending on the balance between kinase activity and the activity of the arachidonic acid pathway. Distinctive hemichannel responses to pathological stimulation with LPS or bFGF may serve to optimize the cell response, directed at strictly controlling cellular ATP release, switching from direct GJ communication to indirect paracrine signaling, or maximizing cell-protective strategies.

Multiplex PCR was established for differential diagnosis of taeniasis and cysticercosis, including their causative agents. For identification of the parasites, multiplex PCR with cytochrome c oxidase subunit 1 gene yielded evident differential products unique for Taenia saginata and Taenia asiatica and for American/African and Asian genotypes of Taenia solium with molecular sizes of 827, 269, 720, and 984 bp, respectively. In the PCRbased detection of tapeworm carriers using fecal samples, the diagnostic markers were detected from 7 of 14 and 4 of 9 T. solium carriers from Guatemala and Indonesia, respectively. Test sensitivity may have been reduced by the length of time (up to 12 years) that samples were stored and/or small sample volumes (ca. 30 to 50 mg). However, the diagnostic markers were detected by nested PCR in five worm carriers from Guatemalan cases that were found to be negative by multiplex PCR. It was noteworthy that a 720 bp-diagnostic marker was detected from a T. solium carrier who was egg-free, implying that it is possible to detect worm carriers and treat before mature gravid proglottids are discharged. In contrast to T. solium carriers, 827-bp markers were detected by multiplex PCR in all T. saginata carriers. The application of the multiplex PCR would be useful not only for surveillance of taeniasis and cysticercosis control but also for the molecular epidemiological survey of these cestode infections.Taenia solium, Taenia saginata, and Taenia asiatica are known as causative agents of taeniasis in humans. T. solium also causes cysticercosis in humans. In particular, neurocysticercosis caused by larval T. solium cysticerci developed in the central nervous system is the most serious disease characterized by diverse neurologic symptoms, most commonly epileptic seizure (5,20). In contrast to cysticercosis, taeniasis is relatively innocuous, with the adult stages of these cestodes infecting the small intestine of humans and causing a few specific symptoms, such as abdominal pain and nausea (15). However, gravid proglottids filled with eggs expelled from tapeworm carriers serve as a new source of infection for intermediate hosts, particularly in developing countries where sanitary conditions are poor. Therefore, early detection and adequate treatment of taeniasis is important for the prevention of cysticercosis infections. Furthermore, reliable epidemiological information for use in the effective control of taeniasis or cysticercosis, including accurate tools for parasite identification, is needed. To date, proglottids and scolices expelled from tapeworm carriers or cysticerci collected from intermediate hosts have been identified morphologically. In Asian regions, however, T. saginata and T. asiatica are frequently confused due to their morphological similarities. Moreover, a recent study demonstrates that two distinct genotypes of T. solium exist, i.e., Asian and American/African genotypes (14). DNA differential diagnosis is considered very useful for the accurate identification of human taeniid...

No abstract