No abstract

Insomnia is a common problem for people with chronic pain. Cortical GABAergic neurons are part of the neurobiological substrate that underlies homeostatic sleep regulation. In the present study, we confirmed that sciatic nerve ligation caused thermal hyperalgesia and tactile allodynia in mice. In this experimental model for neuropathic pain, we found an increase in wakefulness and a decrease in non-rapid eye movement sleep under a neuropathic pain-like state. Under these conditions, membrane-bound GABA (γ-aminobutyric acid) transporters (GATs) on activated glial fibrillary acidic protein-positive astrocytes were significantly increased in the cingulate cortex, and extracellular GABA levels in this area after depolarization were rapidly decreased by nerve injury. Furthermore, sleep disturbance induced by sciatic nerve ligation was improved by the intracingulate cortex injection of a GAT-3 inhibitor. These findings provide novel evidence that sciatic nerve ligation decreases extracellular-released GABA in the cingulate cortex of mice. These phenomena may, at least in part, explain the insomnia in patients with neuropathic pain. Neuropathic pain-like stimuli suppress the GABAergic transmission with increased GABA (γ-aminobutyric acid) transporters located on activated astrocytes in the cingulate cortex related to sleep disturbance.

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We examined patterns of regional cerebral blood flow (rCBF) abnormalities in 18 patients with major depressive disorder in late life using single photon emission computed tomography (SPECT) and 99mTc-hexamethylpropylenamine oxime (99"Tc-HMPAO). Compared with 13 age-matched controls, relative rCBF was significantly decreased bilaterally in the anterior cingulate gyrus, the prefiontal cortex, the temporal cortex, the parietal cortex, the hippocampus and the caudate nucleus. However, it was not correlated with the severity of depression or global cognitive dyshnction. In 10 patients with a prolonged depressive episode or prolonged residual symptoms (the refractory subgroup), robust and extensive decreases in rCBF were found compared with controls and the rCBF decreased significantly in the anterior cingulate gyrus and the prefrontal cortex compared with that in the non-refractory subgroup. In the non-refractory subgroup, rCBF decreased significantly in the caudate nucleus and tended to decrease in the anterior cingulate gyrus compared with controls. These findings indicate that dysfunction of the limbic system, the cerebral association cortex and the caudate nucleus may be implicated in late-life depression and that robust and extensive hypoperfhion, especially in the anterior cingulate and the prefrontal regions, may relate to refractoriness or chronification of depression.

1. In forest communities, the Janzen-Connell (J-C) model proposes that species diversity is maintained by noncompetitive distance-or density-dependent seedling mortality caused by host-specific natural enemies. Host specificity, however, has not been fully elucidated. 2. We conducted a cross-inoculation experiment to evaluate the host specificity of a pathogenic fungus, Colletotrichum anthrisci. The fungus was isolated from seedlings of four tree species (Prunus grayana, Fraxinus lanuginosa, Cornus controversa and Magnolia obovata), all of which were killed by damping-off disease beneath conspecific adults. Each fungal isolate was then inoculated into seedlings of P. grayana and F. lanuginosa. Molecular identification [internal transcribed spacer (ITS) sequences] also confirmed that all isolates (strains) showed 99-100% similarity with C. anthrisci, irrespective of their origin. 3. In both P. grayana and F. lanuginosa seedlings, all isolates of the pathogen caused damage, irrespective of origin, but the damage was more severe with the isolate from conspecifics rather than from any of the three heterospecifics. 4. In response to infection, callose papillae were deposited on the inner side of the leaf cell wall of seedlings in P. grayana; then, circular abscission layers formed between two layers of leaf cells surrounding the locus of infection. The central area of the infection was completely cut off from the rest of the leaf. In F. lanuginosa, infected leaves of seedlings were shed immediately after inoculation. This defensive behaviour, which may prevent further pathogen invasion, was more frequent in seedlings inoculated with isolates from conspecifics than from heterospecifics in both species. 5. Synthesis. Although the pathogenic fungus C. anthrisci is ubiquitous and attacks a wide range of host species, virulence was much stronger for strains derived from conspecifics rather than from heterospecifics, suggesting local adaptation and development of host specificity. If host specificity is common for several pathogens within a microbial community in a given area occupied by an adult, and the trait is also common for multiple tree species co-occurring within a forest community, the J-C model would be applicable to explain tree species diversity.