myelin-basic-protein and Learning-Disabilities

Mature brain-derived neurotrophic factor has shown promotive effect on neural cells in rodents, including neural proliferation, differentiation, survival, and synaptic formation. Conversely, the precursor of brain-derived neurotrophic factor (proBDNF) has been emerging as a differing protein against its mature form, for its critical role in aging process and neurodegenerative diseases. In the present study, we investigated the role of proBDNF in neurogenesis in the hippocampal dentate gyrus of aged mice and examined the changes in mice learning and memory functions. The results showed that the newborn cells in the hippocampus revealed a significant decline in proBDNF-treated group compared with bovine serum albumin group, but an elevated level in anti-proBDNF group. During the maturation period, no significant change was observed in the proportions of phenotype of the newborn cells among the three groups. In water maze, proBDNF-treated mice had poorer scores in place navigation test and probe test, compared with those from any other group. Thus, we conclude that proBDNF attenuates neurogenesis in the hippocampus and induces the deficits in learning and memory functions of aged mice.

Topics: Aging; Analysis of Variance; Animals; Brain-Derived Neurotrophic Factor; Bromodeoxyuridine; Female; Hippocampus; Learning Disabilities; Maze Learning; Memory Disorders; Mice; Mice, Inbred C57BL; Myelin Basic Protein; Nerve Tissue Proteins; Neurogenesis; Protein Precursors; Swimming; Time Factors

Hippocampus learning disturbance is a major symptom of patients with seizure, hence hippocampal dysfunction has essential role in worsening the disease. Hippocampal formation includes neurons and myelinated fibers that are necessary for acquisition and consolidation of memory, long-term potentiation and learning activity. The exact mechanism by which seizure can decrease memory and learning activity of hippocampus remains unknown. In the present study, electrical kindling-induced learning deficit in rats was evaluated by Morris water maze (MWM) test. The hippocampus was removed and changes in neurons and myelin sheaths around hippocampal fibers were investigated using histological and immunohistochemical methods. Demyelination was assessed by luxol fast blue staining, and immunohistological staining of myelin-binding protein (MBP). The TUNEL assay was used for evaluation of neuronal apoptosis and the glial fibriliary acetic protein (GFAP) was used for assessment of inflammatory reaction. The results indicated that electrical kindling of hippocampus could induce deficiency in spatial learning and memory as compared to control group. In addition, electrical kindling caused damage to the myelin sheath around hippocampal fibers and produced vast demyelination. Furthermore, an increase in the number of apoptotic cells in hippocampal slices was observed. In addition, inflammatory response was higher in kindled animals as compared to the control group. The results suggested that the decrease in learning and memory in kindled animals is likely due to demyelination and augmentation in apoptosis rate accompanied by inflammatory reaction in hippocampal neurons of kindled rats.

Topics: Animals; Apoptosis; Avoidance Learning; Demyelinating Diseases; Disease Models, Animal; Electron Transport Complex IV; Excitatory Amino Acid Antagonists; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Hippocampus; Indoles; Ketamine; Kindling, Neurologic; Learning Disabilities; Locomotion; Male; Maze Learning; Myelin Basic Protein; Rats; Rats, Wistar; Reaction Time; Seizures