Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons.

Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA. The significance of such a domain in a plasticity molecule is uncertain. Here, we report that the Drosophila Arc1 protein forms capsid-like structures that bind darc1 mRNA in neurons and is loaded into extracellular vesicles that are transferred from motorneurons to muscles. This loading and transfer depends on the darc1-mRNA 3' untranslated region, which contains retrotransposon-like sequences. Disrupting transfer blocks synaptic plasticity, suggesting that transfer of dArc1 complexed with its mRNA is required for this function. Notably, cultured cells also release extracellular vesicles containing the Gag region of the Copia retrotransposon complexed with its own mRNA. Taken together, our results point to a trans-synaptic mRNA transport mechanism involving retrovirus-like capsids and extracellular vesicles.

Cingulum bundle integrity associated with delusions of control in schizophrenia: Preliminary evidence from diffusion-tensor tractography.

BACKGROUND: Delusions of control are among the most distinctive and characteristic symptoms of schizophrenia. Several theories have been proposed that implicate aberrant communication between spatially disparate brain regions in the etiology of this symptom. Given that white matter fasciculi represent the anatomical infrastructure for long-distance communication in the brain, the present study investigated whether delusions of control were associated with structural abnormalities in four major white matter fasciculi. METHODS: Ten schizophrenia patients with current delusions of control, 13 patients with no clinical history of delusions of control, and 12 healthy controls underwent a Diffusion-Tensor Imaging (DTI) scan. Deterministic tractography was used to extract the corpus callosum, superior longitudinal fasciculus, arcuate fasciculus, and cingulum bundle. The structural integrity of these four fasciculi was quantified with fractional anisotropy (FA) and compared between groups. RESULTS: The patients with delusions of control exhibited significantly lower FA in all four fasciculi, relative to the healthy controls. Furthermore, the patients with delusions of control also exhibited significantly lower FA in the cingulum bundle relative to patients without a history of this symptom, and this difference remained significant when controlling for between-group differences in global SAPS score and medication dosage. CONCLUSIONS: The results suggest that structural damage to the cingulum bundle may be involved in the etiology of delusions of control, possibly because of its role in connecting the action initiation areas of the premotor cortex with the cingulate gyrus.

Genetic contributions to changes of fiber tracts of ventral visual stream in 22q11.2 deletion syndrome.

Patients with 22q11.2 deletion syndrome (22q11.2DS) represent a population at high risk for developing schizophrenia, as well as learning disabilities. Deficits in visuo-spatial memory are thought to underlie some of the cognitive disabilities. Neuronal substrates of visuo-spatial memory include the inferior fronto-occipital fasciculus (IFOF) and the inferior longitudinal fasciculus (ILF), two tracts that comprise the ventral visual stream. Diffusion Tensor Magnetic Resonance Imaging (DT-MRI) is an established method to evaluate white matter (WM) connections in vivo. DT-MRI scans of nine 22q11.2DS young adults and nine matched healthy subjects were acquired. Tractography of the IFOF and the ILF was performed. DT-MRI indices, including Fractional anisotropy (FA, measure of WM changes), axial diffusivity (AD, measure of axonal changes) and radial diffusivity (RD, measure of myelin changes) of each of the tracts and each group were measured and compared. The 22q11.2DS group showed statistically significant reductions of FA in IFOF in the left hemisphere. Additionally, reductions of AD were found in the IFOF and the ILF in both hemispheres. These findings might be the consequence of axonal changes, which is possibly due to fewer, thinner, or less organized fibers. No changes in RD were detected in any of the tracts delineated, which is in contrast to findings in schizophrenia patients where increases in RD are believed to be indicative of demyelination. We conclude that reduced axonal changes may be key to understanding the underlying pathology of WM leading to the visuo-spatial phenotype in 22q11.2DS.

A selective review of volumetric and morphometric imaging in schizophrenia.

Brain imaging studies have long supported that schizophrenia is a disorder of the brain, involving many discrete and widely spread regions. Generally, studies have shown decreases in cortical gray matter (GM) volume. Here, we selectively review recent papers studying GM volume changes in schizophrenia subjects, both first-episode (FE) and chronic, in an attempt to quantify and better understand differences between healthy and patient groups. We focused on the cortical GM of the prefrontal cortex, limbic and paralimbic structures, temporal lobe, and one subcortical structure (the caudate nucleus). We performed a search of the electronic journal database PsycINFO using the keywords "schizophrenia" and "MRI," and selected for papers published between 2001 and 2008. We then screened for only those studies utilizing manual or manually edited tracing methodologies for determining regions of interest (ROIs). Each region of interest was indexed independently; thus, one paper might yield results for numerous brain regions. Our review found that in almost all ROIs, cortical GM volume was decreased in the patient populations. The only exception was the caudate nucleus - most studies reviewed showed no change, while one study showed an increase in volume; this region, however, is particularly sensitive to medication effects. The reductions were seen in both FE and chronic schizophrenia. These results clearly support that schizophrenia is an anatomical disorder of the brain, and specifically that schizophrenia patients tend to have decreased cortical GM in regions involved in higher cognition and emotional processing. That these reductions were found in both FE and chronic subjects supports that brain abnormalities are present at the onset of illness, and are not simply a consequence of chronicity. Additional studies assessing morphometry at different phases of the illness, including prodromal stages, together with longitudinal studies will elucidate further the role of progression in this disorder.