Compartment and cell-type specific hypoxia responses in the developing Drosophila brain.

Environmental factors such as the availability of oxygen are instructive cues that regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain of Drosophila The biosensor reveals brain compartment and cell-type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state of that cell. Our study indicates that oxygen availability appears to be the major factor controlling the hypoxia response in the developing Drosophila brain and that cell intrinsic and cell-type specific factors contribute to modulate the response in an unexpected manner.This article has an associated First Person interview with the first author of the paper.

Molecular characterization and distribution of the voltage-gated sodium channel, Para, in the brain of the grasshopper and vinegar fly.

Voltage-gated sodium (NaV) channels, encoded by the gene para, play a critical role in the rapid processing and propagation of visual information related to collision avoidance behaviors. We investigated their localization by immunostaining the optic lobes and central brain of the grasshopper Schistocerca americana and the vinegar fly Drosophila melanogaster with an antibody that recognizes the channel peptide domain responsible for fast inactivation gating. NaV channels were detected at high density at all stages of development. In the optic lobe, they revealed stereotypically repeating fascicles consistent with the regular structure of the eye. In the central brain, major axonal tracts were strongly labeled, particularly in the grasshopper olfactory system. We used the NaV channel sequence of Drosophila to identify an ortholog in the transcriptome of Schistocerca. The grasshopper, vinegar fly, and human NaV channels exhibit a high degree of conservation at gating and ion selectivity domains. Comparison with three species evolutionarily close to Schistocerca identified splice variants of Para and their relation to those of Drosophila. The anatomical distribution of NaV channels molecularly analogous to those of humans in grasshoppers and vinegar flies provides a substrate for rapid signal propagation and visual processing in the context of visually-guided collision avoidance.

Ferritin overexpression in Drosophila glia leads to iron deposition in the optic lobes and late-onset behavioral defects.

Cellular and organismal iron storage depends on the function of the ferritin protein complex in insects and mammals alike. In the central nervous system of insects, the distribution and relevance of ferritin remain unclear, though ferritin has been implicated in Drosophila models of Alzheimers' and Parkinsons' disease and in Aluminum-induced neurodegeneration. Here we show that transgene-derived expression of ferritin subunits in glial cells of Drosophila melanogaster causes a late-onset behavioral decline, characterized by loss of circadian rhythms in constant darkness and impairment of elicited locomotor responses. Anatomical analysis of the affected brains revealed crystalline inclusions of iron-loaded ferritin in a subpopulation of glial cells but not significant neurodegeneration. Although transgene-induced glial ferritin expression was well tolerated throughout development and in young flies, it turned disadvantageous at older age. The flies we characterize in this report contribute to the study of ferritin in the Drosophila brain and can be used to assess the contribution of glial iron metabolism in neurodegenerative models of disease.

Identity of the cells recruited to a lesion in the central nervous system of a decapod crustacean.

In a previous study, we analyzed and described the features of the degeneration of the protocerebral tract (PCT) of the crustacean Ucides cordatus, after the extirpation of the eyestalk. In that study, among axons with axoplasmic degeneration, cells with granules resembling blood cells (hemocytes) were seen. Therefore, in the present study, we characterized the circulating hemocytes and compared them with the cells recruited to a lesion, which was produced as in the former study. Using histochemistry, immunohistochemistry, and electron microscopy (transmission and scanning), we confirmed that circulating and recruited cells display a similar morphology. Therefore, in the crab, hemocytes were attracted to the lesion site in the acute stage of degeneration, appearing near local glial cells that showed signs of being responsive. Some of the attracted hemocytes displayed a morphology that was considered to be possibly activated blood cells. Also, the cells that migrated to the injured PCT displayed features, such as the presence of hydrolytic enzymes and an ability to phagocytize neural debris, similar to those of vertebrates. In summary, our results indicate that hemocytes were not only phagocytizing neural debris together with glial cells but also that they may be concerned with creating a favorable environment for regenerating events.

Density and maturation of rodlet cells in brain tissue of fathead minnows (Pimephales promelas) exposed to trematode cercariae.

Evidence for the presumed linkage between the enigmatic rodlet cells of fish and exposure to helminths is anecdotal and indirect. We evaluated the proliferation and development of rodlet cells in the optic lobes of fathead minnows exposed to cercariae of Ornithodiplostomum ptychocheilus. Mean rodlet cell densities (ca. 10/mm(2)) in the optic lobes were similar between unexposed controls and minnows with 1- and 2-week old infections. Rodlet cell densities increased at 4 weeks p.i., reaching maxima (ca. 200/mm(2)) at 6 weeks p.i., followed by a decline at 9 weeks. This temporal pattern of proliferation and maturation paralleled the development of metacercariae within the optic lobes. Unencysted metacercariae develop rapidly within tissues of the optic lobes for approximately 4 weeks after penetration by cercariae, then shift to the adjacent meninges to encyst. The former stage is associated with tissue damage, the latter with massive inflammation of the meninges. Thus, peak densities and maturation of rodlet cells correspond to the period when inflammation of the meninges caused by the large metacercarial cysts is at a maximum. Our results support recent contentions that rodlet cells comprise part of the host inflammatory defence response.

The conserved Ig superfamily member Turtle mediates axonal tiling in Drosophila.

Restriction of adjacent same-type axons/dendrites to separate single columns for specific neuronal connections is commonly observed in vertebrates and invertebrates, and is necessary for proper processing of sensory information. Columnar restriction is conceptually similar to tiling, a phenomenon referring to the avoidance of neurites from adjacent same-type neurons. The molecular mechanism underlying the establishment of columnar restriction or axonal/dendritic tiling remains largely undefined. Here, we identify Turtle (Tutl), a member of the conserved Tutl/Dasm1/IgSF9 subfamily of the Ig superfamily, as a key player in regulating the tiling pattern of R7 photoreceptor terminals in Drosophila. Tutl functions to prevent fusion between two adjacent R7 terminals, and acts in parallel to the Activin pathway. Tutl mediates homophilic cell-cell interactions. We propose that extrinsic terminal-terminal recognition mediated by Tutl, acts in concert with intrinsic Activin-dependent control of terminal growth, to restrict the connection made by each R7 axon to a single column.

An extract of Hydrilla verticillata and associated epiphytes induces avian vacuolar myelinopathy in laboratory mallards.

Avian vacuolar myelinopathy (AVM) is a neurological disease affecting bald eagles (Haliaeetus leucocephalus), American coots (Fulica americana), waterfowl, and other birds in the southeastern United States. The cause of the disease is unknown, but is thought to be a naturally produced toxin. AVM is associated with aquatic macrophytes, most frequently hydrilla (Hydrilla verticillata), and researchers have linked the disease to an epiphytic cyanobacterial species associated with the macrophytes. The goal of this study was to develop an extraction protocol for separating the putative toxin from a hydrilla-cyanobacterial matrix. Hydrilla samples were collected from an AVM-affected reservoir (J. Strom Thurmond Lake, SC) and confirmed to contain the etiologic agent by mallard (Anas platyrhynchos) bioassay. These samples were then extracted using a solvent series of increasing polarity: hexanes, acetone, and methanol. Control hydrilla samples from a reference reservoir with no history of AVM (Lake Marion, SC) were extracted in parallel. Resulting extracts were administered to mallards by oral gavage. Our findings indicate that the methanol extracts of hydrilla collected from the AVM-affected site induced the disease in laboratory mallards. This study provides the first data documenting for an "extractable" AVM-inducing agent.

Experimental vacuolar myelinopathy in red-tailed hawks.

Avian vacuolar myelinopathy (AVM) was recognized in 1994 as a cause of wild bird mortality when 29 bald eagles (Haliaeetus leucocephalus) succumbed to the disease at DeGray Lake, Arkansas (USA). The cause of AVM and its source remain undetermined despite extensive diagnostic and research investigations. Two years later, when AVM killed 26 eagles in the same area in Arkansas, it became apparent that American coots (Fulica americana) had identical neurologic signs and lesions, and it was hypothesized that eagles acquired AVM via ingestion of affected coots. In order to test this hypothesis, we fed coot tissues (brain, liver, kidney, muscle, fat, and intestinal tract) to rehabilitated, non-releasable red-tailed hawks (Buteo jamaicensis). Five hawks received tissues from coots with AVM lesions, and one hawk received tissues from coots without brain lesions that had been collected at a site where AVM never has been documented. All hawks received 12-70 g/day (mean = 38 g) of coot tissues for 28 days. All six hawks remained clinically normal during the study. The birds were euthanatized on day 29 and microscopic lesions of AVM were found in all hawks that received tissues from affected coots, but not in the hawk that received tissues from unaffected coots. This marks the first time that AVM has been produced in birds under laboratory conditions and proves that birds of prey can acquire AVM via ingestion of tissues from affected coots.

Vacuolar myelinopathy in waterfowl from a North Carolina impoundment.

Vacuolar myelinopathy was confirmed by light and electron microscopic examination of mallards (Anas platyrhynchos), ring-necked ducks (Aythya collaris), and buffleheads (Bucephala albeola) collected during an epizootic at Lake Surf in central North Carolina (USA) between November 1998 and February 1999. Clinical signs of affected birds were consistent with central nervous system impairment of motor function (incoordination, abnormal movement and posture, weakness, paralysis). This is the first report of this disease in wild waterfowl (Anseriformes).

Treatment with 6-hydroxydopamine in planaria (Dugesia gonocephala s.l.): morphological and behavioral study.

Morpho-functional and behavioral effects of exposure to 6-hydroxydopamine (OHDA)-HCI (24 microg/ml per day for 24 h and 7 days) were studied in planarias (Dugesia gonocephala s.l.). Exposure to 6-OHDA-HC1 for 24 h produced hypokinesia of the specimens. These behavioral changes were more pronounced, leading to complete immobility, after 7 days of exposure to the neurotoxin. Moreover, specimens exposed to 6-OHDA-HCI for 24 h and 7 days failed to show any behavioral response to nomifensine, thus furnishing evidence of the damage of presynaptic dopamine terminals. Exposure to 6-OHDA-HCl for 24 h significantly reduced cathecolamine content in neuropil region, as demonstrated by histochemistry, and electron-dense presynaptic vesicles, as observed on electron microscopy examination. All these alterations were significantly more pronounced and were accompanied by swelling and strong increase of electron-density in cytoplasm of numerous neurons after exposure to the neurotoxin for 7 days. This appears to be the first demonstration of the neurotoxic effects of 6-OHDA-HCI in flatworms.

Clinoidal meningioma arising from falciforme process of optic canal: case report and review.

A 56-year-old female with an initial symptom of unilateral progressive visual disturbance presented with a clinoidal meningioma arising from a falciforme process of the optic canal. Magnetic resonance images with gadolinium-diethylenetriaminepenta-acetic acid demonstrated marked enhancement of a small mass, approximately 1 cm in diameter, roofing the right optic nerve at the intracranial opening of the optic canal. The clinoidal meningioma is rarely reported and the precise originating location of the neoplasm has not been clarified. This is the first case of clinoidal meningioma, which is confirmed by the operative observation as the origin of the neoplasm is a falciforme process of the optic canal. Magnetic resonance images with enhancement are useful for the diagnosis of such a small neoplastic lesion adjacent to bone structure and total removal without a deterioration of visual function is achieved by careful microsurgical procedure.

Behavioural and neurohistological changes in aging Sepia.

The life cycle of the cuttlefish in the English Channel is characterized by a succession of homogeneous population cohorts. These conditions provide an excellent opportunity for the study of aging in this cephalopod. In a first longitudinal study, we considered the oldest animals and compared their success rates at the first capture attempt. During the first weeks of the study, the results remained constant and then, during the weeks immediately preceding the natural death, a dramatic drop was observed. This deterioration may be due to defects of visuomotor coordination. In a second study, we used an associative learning protocol with negative reinforcement and the performances of young and old animals were compared. The most striking results showed that the performances of the oldest animals during the retention test were very mediocre. Such results suggest that the long-term memory process is affected. Finally, a modification of the Fink-Heimer silver stain enabled us to draw a map of spontaneous terminal degeneration in the central nervous system of the oldest animals. The structures which are characterized by the presence of multimodal inputs (the spine of the peduncle lobe and the basal lobes) present the most obvious signs of degeneration.

Behavioral effects of cyclic dosing with methylmercury in pigeons.

The present experiments examined the effects of cyclic dosing with methylmercury (MeHg) on some psychological functions in pigeons. A delayed sequence discrimination task involving order competency and a feeding task involving perceptual motor skill were tested in pigeons dosed with 2.0 mg/kg, 0.5 mg/kg, or no MeHg (the control group) during cycles of brief daily MeHg exposure and extended behavioral testing. Performance in the sequence discrimination and the feeding task was affected after a cumulative dose of only 20 mg/kg in the 2.0 mg/kg group. Sequence discrimination recovered within three months after dosing when MeHg was stopped, but feeding skill did not recover over the remainder of the experiment (about 4 1/2 months later). A cumulative dose of 86 mg/kg in the 0.5 mg/kg group had no observable effect on either task.

[Changes of orbitofrontal astroglia in senile dementia (author's transl)]. / Uber Astrozytenveränderungen in der orbitofrontalen Hirnrinde bei seniler Demenz.

The changes of orbitofrontal studied astroglia in 10 cases of senile dementia have been studied. The modification of Golgi-method by Bubenaite was used. The results reveal 4 different types of changed astroglia. A relation between changes of makroglia and the aging process of CNS is suggested. The changes of glia are not a result of nervous cell alterations, but an independent neuroglial process under the conditions of aging.