ABSTRACT
Disruption of neuronal networks in the Alzheimer-afflicted brain is increasingly recognized as a key correlate of cognitive and memory decline in Alzheimer patients. We hypothesized that functional synaptic disconnections within cortical columnar microcircuits by pathological ß-amyloid accumulation, rather than cell death, initially causes the cognitive impairments. During development of cortical ß-amyloidosis with still few plaques in the transgenic 5xFAD mouse model single cell resolution mapping of neuronal thallium uptake revealed that electrical activity of pyramidal cells breaks down throughout infragranular cortical layer V long before cell death occurs. Treatment of 5xFAD mice with the glutaminyl cyclase inhibitor, PQ 529, partially prevented the decline of pyramidal cell activity, indicating pyroglutamate-modified forms, potentially mixed oligomers of Aß are contributing to neuronal impairment. Laminar investigation of cortical circuit dysfunction with current source density analysis identified an early loss of excitatory synaptic input in infragranular layers, linked to pathological recurrent activations in supragranular layers. This specific disruption of normal cross-laminar cortical processing coincided with a decline of contextual fear learning.
Subject(s)
Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Cerebral Cortex/pathology , Plaque, Amyloid/etiology , Age Factors , Alzheimer Disease/genetics , Amyloid beta-Protein Precursor/genetics , Animals , Cell Death/physiology , Cerebral Cortex/metabolism , Conditioning, Psychological , Disease Models, Animal , Fear , Fourier Analysis , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mutation/genetics , Neurons/metabolism , Neurons/pathology , Plaque, Amyloid/genetics , Presenilin-1/genetics , ThalliumABSTRACT
Successful early reading and spelling acquisition depends on a number of different skills. Of considerable importance is phonological processing, which is the processing of acoustic signals with linguistic content. Three areas of phonological processing have been found to be most important for reading and writing competence: phonological awareness, naming speed, and phonological working memory. Research on these components suggests that specific interventions tailored to individual phonological processing deficits may prevent later dyslexia. Therefore, it appears mandatory that ear-nose-throat physicians have at least a basic knowledge of the theory of phonological processing. This will enable proper consultation with parents of affected children.
Subject(s)
Dyslexia/diagnosis , Dyslexia/physiopathology , Phonetics , Reading , Verbal Learning , Adolescent , Child , Child, Preschool , Educational Status , Humans , Infant , Infant, NewbornABSTRACT
PIP: The crystallized mineral deposits on 91 copper IUDs removed by normal procedures were analyzed using x-ray diffraction. 50 Nova-T, 27 Multiload 375, and 14 Gravigard devices were divided into a group of 32 in place for 10-36 months and a group of 59 in place for over 36 months. Studies were performed by x-ray diffraction on whole IUDs in the fresh or dry state and by using classic x-ray, infrared, and atomic absorption spectrometry methods on deposits. Coils of all the IUDs were covered with a layer of cuprous oxide adherent to the metal that flaked over time. Crystals or coatings formed white deposits on 63% of all IUDs, especially when cuprous oxide adhered to the metal. The deposits covered 65-85% of adherent oxides and only 33-38% of flaked oxides for the 1st and 2nd durations of use respectively. Deposits were more abundant on Nova T and Gravigard than on Multiload devices. For the short and long periods of use, the respective frequencies were 67 and 74% on Nova Ts, 25 and 47% on Multiloads, and 88 and 67% on Gravigard. Calcium carbonate (CaCO3) was the only crystalline inorganic compound found, and was present with or without white deposit on 80% of IUDs. It was in the form of calcite, accompanied by vaterite in 40% of cases and rarely by aragonite. Calcium was substituted by magnesium, with an average of 3.7 atoms. Sodium, potassium, and excess magnesium were not in the organic crystalline phase.^ieng
