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
The term "chronic illness" subsumes a multitude of conditions and complaints, all of varying development. It is often impossible to establish a prognosis and only seldom is causal therapy available. A chronic illness or handicap must be seen as fate, not only for the affected child but also for his or her family. Both require concerned and competent support towards mastering their situation in a justifiably realistic way. A highly developed network must be available to families of chronically ill children to help them prevent and overcome crisis. The organization of this network requires much planning and effort. In many families with chronically ill or handicapped children the ability to develop and to make decisions can only be regained when the hopelessness and helplessness involved in having a severely chronically ill child has been recognized and accepted by all concerned.
Subject(s)
Adaptation, Psychological , Chronic Disease/psychology , Parents/psychology , Psychology, Child , Adult , Child , Crisis Intervention , Humans , Professional-Family Relations , Respite Care , Social SupportABSTRACT
The increased permeability of the blood-brain barrier during acute inflammation of the central nervous system leads to changes of the cerebrospinal fluid (C.S.F.) protein pattern. Initially, in the cases of bacterial meningitis, cellulos acetate electrophoresis revealed decreased prealbumin, albumin and tau-globulin fraktion whereas alpha- and gamma-globulin fractions were found increased. In later stages of purulent inflammation a hydrocephalus occurred in five children, associated with an increased amount of albumin in the C.S.F. Cases of viral meningoencephalitis had a characteristic decrease of prealbumin and increase of gamma-globulin, the lowered prealbumin values were found more often. In three cases of congenital encephalitis pathological patterns of C.S.F. proteins were still found 1--1 1/2 years postpartum. Children with acute peripheral facial palsy and febrile convulsions had a normal C.S.F. protein profile.
