tetracycline and Memory-Disorders

Neuronal loss is a major pathological outcome of many common neurological disorders, including ischemia, traumatic brain injury, and Alzheimer disease. Stem cell-based approaches have received considerable attention as a potential means of treatment, although it remains to be determined whether stem cells can ameliorate memory dysfunction, a devastating component of these disorders. We generated a transgenic mouse model in which the tetracycline-off system is used to regulate expression of diphtheria toxin A chain. After induction, we find progressive neuronal loss primarily within the hippocampus, leading to specific impairments in memory. We find that neural stem cells transplanted into the brain after neuronal ablation survive, migrate, differentiate and, most significantly, improve memory. These results show that stem cells may have therapeutic value in diseases and conditions that result in memory loss.

Topics: Analysis of Variance; Animals; Behavior, Animal; Brain Diseases; Bromodeoxyuridine; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cell Count; Cell Differentiation; Cell Movement; Cell Proliferation; Diphtheria Toxin; Disease Models, Animal; Green Fluorescent Proteins; In Situ Nick-End Labeling; Memory Disorders; Mice; Mice, Transgenic; Neurons; Peptide Fragments; Phosphopyruvate Hydratase; Stem Cell Transplantation; Tetracycline

Four patients with Whipple's disease which had responded to antibiotic therapy, later developed neurologic disease identical to that seen in patients with Whipple's disease who died without treatment. Dementia, myoclonus, ataxia, and supranuclear ophthalmoplegia were the main neurologic features. Restarting antibiotics has been followed by stabilization of disease in all four. Two have improved. In three, the previously diagnosed and treated Whipple's disease was not considered as a possible cause of the neurologic disease until the symptoms and signs were far advanced. It is advisable to periodically evaluate all patients with Whipple's disease, even after successful treatment. Signs of neurologic disease should be considered a possible recurrence of Whipple's disease and antibiotics restarted.

Topics: Adult; Anti-Bacterial Agents; Dementia; Female; Humans; Male; Memory Disorders; Middle Aged; Nervous System Diseases; Penicillins; Tetracycline; Whipple Disease