ABSTRACT
OBJECTIVE: The aim of this study was to investigate whether anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance in stroke patients. DESIGN: Twelve stroke patients with audioverbal memory impairment participated in a single-masked, crossover, and sham-controlled experiment. The anodal or sham transcranial direct current stimulation was applied during the Rey Auditory Verbal Learning Test, which evaluates the ability to recall a list of 15 heard words over five trials. The number of correctly recalled words was compared between the anodal and sham conditions and the influence of transcranial direct current stimulation on serial position effect of the 15 words was also examined. RESULTS: The increase in the number of correctly recalled words from the first to the fifth trial was significantly greater in the anodal condition than in the sham condition (P < 0.01). There was a significant difference (P < 0.01) between the anodal and sham conditions in the number of correctly recalled words within the first five words (primacy region) over the second to fifth trial trials, but not in the middle (next five words) or recency (last five words) regions. CONCLUSIONS: Anodal transcranial direct current stimulation over the left temporoparietal area improved audioverbal memory performance and induced the primacy effect in stroke patients.
Subject(s)
Memory Disorders/therapy , Mental Recall , Stroke/psychology , Transcranial Direct Current Stimulation/methods , Aged , Cross-Over Studies , Female , Humans , Male , Memory Disorders/etiology , Memory Disorders/physiopathology , Parietal Lobe/physiopathology , Single-Blind Method , Stroke/complications , Stroke/therapy , Temporal Lobe/physiopathology , Treatment OutcomeABSTRACT
Kidney development and physiology require polarization of epithelia that line renal tubules. Genetic studies show that polarization of invertebrate epithelia requires the crumbs, partition-defective-3, and discs large complexes. These evolutionarily conserved protein complexes occur in mammalian kidney; however, their role in renal development remains poorly defined. Here, we find that mice lacking the small PDZ protein mammalian LIN-7c (MALS-3) have hypomorphic, cystic, and fibrotic kidneys. Proteomic analysis defines MALS-3 as the only known core component of both the crumbs and discs large cell polarity complexes. MALS-3 mediates stable assembly of the crumbs tight junction complex and the discs large basolateral complex, and these complexes are disrupted in renal epithelia from MALS-3 knockout mice. Interestingly, MALS-3 controls apico-basal polarity preferentially in epithelia derived from metanephric mesenchyme, and defects in kidney architecture owe solely to MALS expression in these epithelia. These studies demonstrate that defects in epithelial cell polarization can cause cystic and fibrotic renal disease.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Kidney/pathology , Multiprotein Complexes/physiology , Adaptor Proteins, Signal Transducing/physiology , Amino Acid Sequence , Animals , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/physiology , Cell Cycle Proteins , Epithelial Cells/metabolism , Kidney/embryology , Kidney/metabolism , Membrane Proteins/metabolism , Membrane Proteins/physiology , Mice , Mice, Knockout , Molecular Sequence Data , Multiprotein Complexes/genetics , Multiprotein Complexes/metabolism , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/physiology , Organogenesis/genetics , Protein Subunits/genetics , Protein Subunits/metabolism , Sequence Alignment , Tight Junctions/metabolism , Tight Junctions/pathologyABSTRACT
Synapses are highly specialized intercellular junctions organized by adhesive and scaffolding molecules that align presynaptic vesicular release with postsynaptic neurotransmitter receptors. The MALS/Veli-CASK-Mint-1 complex of PDZ proteins occurs on both sides of the synapse and has the potential to link transsynaptic adhesion molecules to the cytoskeleton. In this study, we purified the MALS protein complex from brain and found liprin-alpha as a major component. Liprin proteins organize the presynaptic active zone and regulate neurotransmitter release. Fittingly, mutant mice lacking all three MALS isoforms died perinatally with difficulty breathing and impaired excitatory synaptic transmission. Excitatory postsynaptic currents were dramatically reduced in autaptic cultures from MALS triple knockout mice due to a presynaptic deficit in vesicle cycling. These findings are consistent with a model whereby the MALS-CASK-liprin-alpha complex recruits components of the synaptic release machinery to adhesive proteins of the active zone.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Carrier Proteins/metabolism , Membrane Proteins/metabolism , Neurotransmitter Agents/metabolism , Presynaptic Terminals/metabolism , Adaptor Proteins, Signal Transducing/genetics , Animals , Carrier Proteins/genetics , Cells, Cultured , Female , Gene Targeting , Macromolecular Substances/metabolism , Male , Membrane Proteins/genetics , Mice , Mice, Knockout , Neurons/physiology , Particle Size , Patch-Clamp Techniques , Proteomics , Synaptic Transmission/genetics , Two-Hybrid System Techniques , Vesicular Transport ProteinsABSTRACT
A 79-year-old woman, with no immune deficit, had presented progressive visual disturbance, diplopia and ptosis of her left eye over 2 weeks. T1-weighted MR images with gadolinium showed a heterogeneously enhanced lesion extending from the left orbital apex along the optic nerve to the cavernous sinus. Although we could not detect fungus by a transsphenoidal biopsy, we suspected fungal infection because of high level of galactomanan antigen in serum. Despite antifungal chemotherapy, her symptoms did not improve. CT image on day 40 showed an aneurysm in the left internal carotid artery, on day 43 cerebral infarction in the left internal carotid artery distribution and on day 45 she died. Autopsy disclosed that aspergillus hyphae invaded the left sphenoid sinus, cavernous sinus and wall of the aneurysm. In this case, fungal infection in the frontal skull base including orbital apex caused mycotic aneurysm in the intracavernous portion of the left internal carotid artery. Skull base aspergillosis presenting orbital apex syndrome is itself rare and in addition, the occurrence of cerebral infarction in the mycotic aneurysm has hardly been reported. We should have cerebrovascular disease in mind as a complication of CNS aspergillosis.
