Ultrastructural Immunocytochemistry of GABAergic Cells in Neocortical Neurotransplants.

Neural transplantation is a promising regenerative therapy in the treatment of several neurological diseases. Importantly, transplanted tissue should not become a source of pathological functional activity. To assess the possibility of maintaining the balance between excitatory and inhibitory processes, an electron microscopic immunochemical study of the GABAergic system in rat neocortical transplants was performed. Accumulation of GABA-positive label in astrocytes and a relatively insignificant immune reaction to GABA in neurons and synaptic endings were found. These findings suggest that under conditions of impaired differentiation of GABA-containing neurons that generate phasic inhibition through inhibitory synapses, tonic inhibitory influences predominate in neurotransplants due to GABA released from astrocytes.

Analysis of the Effect of Neuroprotectors That Reduce the Level of Degeneration of Neurons in the Rat Hippocampus Caused by Administration of Beta-Amyloid Peptide Aß25-35.

Deposition of beta-amyloid peptide in the brain observed in Alzheimer's disease contributes to the development of cognitive deficits. We studied the abilities of different neuroprotectors to prevent or reduce degeneration of hippocampal neurons in rat brain 14 and 45 days after single intrahippocampal injection of beta-amyloid peptide 25-35 (Aß25-35). Cytological analysis of the neurons of the hippocampal CA1 and CA3 fields showed predominant damage to CA1 neurons in 14 days and CA3 neurons in 45 days after Aß25-35 administration. Single preliminary administrations of neuroprotectors fullerene C60FWS (antioxidant), neuromedin (nonselective inhibitor of acetylcholinesterase), and AM404 (activator of the endocannabinoid system) largely prevented neurodegeneration of neurons. Fullerene produced the most pronounced protective effect, which can be explained by its ability to prevent aggregation of proteins and destroy Aß25-35 fibrils. The combined use of these neuroprotectors can provide the basis for the development of new approaches to prevention and treatment of Alzheimer's disease.

Dopamine Improves Resistance of Dendrites of Mauthner Neurons to Destruction Induced by Sensory Stimulation and Application of Β-Amyloid.

Mauthner neurons in goldfish fry were studied by the methods of light and electron microscopy. The structure and volume of individual dendrites as well as the structure of axodendritic synapses were examined using virtual images of neurons formed from serial 3-µ sections. In short-time (5 h) experiments with application of dopamine, ß-amyloid fragment (25-35), and long-term sensory stimulation affecting afferent inputs to Mauthner neurons, the dendrites were larger than the same dendrites under the same conditions without dopamine application. Application of dopamine induced no pathological changes in the structure of axodendritic chemical and electric synapses containing desmosome-like contacts.

Ultrastructural Alterations in Granular Neurons of the Dentate Fascia Caused by Intrahippocampal Injection of Beta-Amyloid 1-42.

The deposition of beta-amyloid (Aß) in the brain is detected in Alzheimer's disease and during ageing. Until now, ultrastructural studies of changes caused by Aß in the dentate gyrus are very scarce. The effects of Aß 1-42 injection into the CA1 field of rat hippocampus were studied by electron microscopy. In 2 weeks after injection of aggregated Aß in low concentrations, destructive changes were seen in the structure of dentate gyrus cells, which consisted in a decrease in the number of dentate gyrus neurons and axo-dendritic synapses. These changes were accompanied by enlargement of the endoplasmic reticulum cisterns and widening of the active zones of synapses. Thus, injection of aggregated Aß 1-42 into the hippocampus led to irreversible (a decrease in the number of neurons and axo-dendritic synapses, agglutination of synthetic vesicles) and adaptive changes (an increase in the sizes of endoplasmic reticulum cisterns and active zones of synapses) in dentate gyrus neurons aimed at the maintenance of functional activity of the nervous system.

Intraocular Neurografts as a Model for Studying of Organization of Synaptic Connections in a Denervated Brain Area.

Intraocular neurografts of the septal region of rats were used as the model of deafferentiated brain area where the lack of adequate innervation is compensated for own interneuronal connections. Septum anlage from the brain of a 17-day fetus served as the donor material. The grafts developing in the anterior eye chamber over 3 months represented well-differentiated samples of the nervous tissue. A comparative morphometric study of the tripartite organization of synapses in the grafts and in the septum in situ was conducted. In the grafts, the mean volume and perimeter of synaptic terminals were below the normal. At the same time, postsynaptic densities did not differ from the control. A significant difference was found in the degree of surrounding of presynaptic terminals by astrocytic processes: in the grafts this parameter was higher by 1.8 times. Our results attest to an important role of perisynaptic glia in the formation of functionally active synaptic contacts with unusual neuronal targets.