ABSTRACT
The possible link between amnesia induced by central administration of beta-amyloid (25-35) (Abeta(25-35)) and neurodegenerative changes in the hippocampus was studied. Male Wistar rats received single intracerebroventricular injections of Abeta(25-35) at a dose of 15 nmoles and one month later were trained in an eight-arm radial maze. Training was followed by histological assessment of the state of the hippocampus on brain sections stained with hematoxylin and eosin. Abeta(25-35) induced impairments in long-term (reference) and working memory on testing in the maze. There was a moderate reduction in the number of neurons in hippocampal field CA1; there was no change in the number of cells in field CA3. The numbers of errors made by the animals on testing in the maze were found to correlate negatively with the numbers of nerve cells in hippocampal field CA1. Thus, this is the first demonstration that impairments of learning and memory induced by single doses of Abeta(25-35) are specifically associated with neurodegenerative changes in hippocampal field CA1 in rats.
Subject(s)
Amyloid beta-Peptides/toxicity , Hippocampus/drug effects , Memory Disorders/chemically induced , Memory Disorders/pathology , Peptide Fragments/toxicity , Animals , Behavior, Animal/drug effects , Cell Count , Hippocampus/pathology , Injections, Intraventricular/methods , Male , Maze Learning/drug effects , Maze Learning/physiology , Memory Disorders/physiopathology , Neurons/pathology , Rats , Rats, WistarABSTRACT
The relationship between convulsive activity evoked by repeated electric shocks and structural changes in the hippocampus of Balb/C mice was studied. Brains were fixed two and seven days after the completion of electric shocks, and sections were stained by the Nissl method and immunohistochemically for apoptotic nuclei (the TUNEL method). In addition, the activity of caspase-3, the key enzyme of apoptosis, was measured in brain areas immediately after completion of electric shocks. The number of neurons decreased significantly in field CA1 and the dentate fascia, but not in hippocampal field CA3. The numbers of cells in CA1 and CA3 were inversely correlated with the intensity of convulsions. Signs of apoptotic neuron death were not seen, while caspase-3 activity was significantly decreased in the hippocampus after electric shocks. These data support the notion that functional changes affect neurons after electric shock and deepen our understanding of this view, providing direct evidence that there are moderate (up to 10%) but significant levels of neuron death in defined areas of the hippocampus. Inverse correlations of the numbers of cells with the extent of convulsive activity suggest that the main cause of neuron death is convulsions evoked by electric shocks.
Subject(s)
Electroshock/adverse effects , Hippocampus/pathology , Neurodegenerative Diseases/pathology , Neurodegenerative Diseases/physiopathology , Neurons/radiation effects , Animals , Caspase 3 , Caspases/metabolism , Cell Count/methods , Cell Death/radiation effects , Disease Models, Animal , Female , Mice , Mice, Inbred BALB C , Neurodegenerative Diseases/etiology , Neurodegenerative Diseases/metabolism , Neurons/metabolism , Neurons/pathologyABSTRACT
A possible relationship between the amnesia induced by central administration of beta-amyloid (25-35) [Abeta(25-35)] and neurodegeneration in the hippocampus was studied. Male Wistar rats received a single intracerebroventricular injection of Abeta(25-35) at a dose of 15 nmol. One month after the administration, animals were trained in an eight-arm radial maze. After the training, a histopathological investigation of the hippocampus was carried out using brain slices stained with hematoxylin/eosin. Abeta(25-35) induced impairments in reference and working memory in the eight-arm radial maze. A moderate decrease in neuronal cell number was demonstrated in the CA1, but not in the CA3 subfield of the hippocampus. The number of both reference and working errors negatively correlated with the number of neurons in hippocampal CA1. The results are the first evidence for a specific relationship between neurodegeneration in the CA1 subfield of rat hippocampus and impairments of learning and memory induced by Abeta(25-35).
Subject(s)
Amyloid beta-Peptides/pharmacology , Hippocampus/pathology , Maze Learning/physiology , Memory/physiology , Peptide Fragments/pharmacology , Space Perception/physiology , Amyloid beta-Peptides/administration & dosage , Animals , Hippocampus/drug effects , Hippocampus/physiopathology , Injections, Intraventricular , Male , Maze Learning/drug effects , Memory/drug effects , Memory Disorders/etiology , Memory Disorders/pathology , Memory Disorders/physiopathology , Neurons/pathology , Neurons/physiology , Peptide Fragments/administration & dosage , Rats , Rats, Wistar , Space Perception/drug effectsABSTRACT
Relations between seizures induced by repeated electroshock (ES) and structural changes in the hippocampus were investigated in Balb/C mice. Brain sections of the animals 2 or 7 days after the last ES were stained for Nissl or TUNEL (apoptotic nuclei). Direct measurement of caspase-3 activity (a key enzyme of apoptosis) in brain regions was performed immediately after the last ES. Statistically significant, albeit moderate cell loss was demonstrated in the CA1 field and dentate gyrus, but not in the CA3 field of the hippocampus. The number of neurons in these fields inversely correlated with seizure severity. No apoptotic nuclei could be revealed either in hippocampus or in other brain regions. Caspase-3 in the hippocampus decreased after ES. The data obtained support the results from other groups showing prominent functional changes in neurons induced by repeated ES and extend this concept directly testifying for a moderate (within 10%), albeit statistically significant neuronal death in selected hippocampal fields. The inverse correlation of cell number with severity of seizures suggest that these are seizures inducing neuronal death.