Neurotransmitter depletion may be a cause of dementia pathology rather than an effect

Medical Hypotheses
Joseph Martin Alisky

Abstract

There is widespread loss of acetylcholine and other neurotransmitters in Alzheimer's disease and vascular dementia. It has generally been assumed that death of neurons causes neurotransmitter loss, but alternatively neurotransmitter depletion itself may at least contribute to neurodegeneration. Transgenic mice and pigs with inducible 50% depletion of acetylcholine, dopamine, norepinephrine, serotonin, gamma-aminobutyric acid (GABA) and corticotrophin releasing factor will reproduce Alzheimer's disease or vascular dementia neuropathology, and pharmacologically restoring neurotransmitters will attenuate neuronal injury. Through nuclear transfer cloning, transgenic mice and pigs would be created with transgenes on one X chromosome, so that transgenes would only be expressed in half of all cells in female animals. Transgenes would encode tetracycline-inducible short hairpin RNA (shRNA) designed to form small interfering RNA (siRNA) to knock down neurotransmitter biosynthesis in late adulthood. Transgene expressing neurons could be readily identified in tissue sections with fluorescent reporter genes. Cholinesterase inhibitors, antidepressants, benzodiazepines and CRF would then be administered in an attempt to rescue degenerating n...Continue Reading

References

Dec 1, 1992·Cellular and Molecular Neurobiology·A J Nazarali, G P Reynolds
Dec 1, 1990·Journal of Neuroscience Research·K J ReinikainenP J Riekkinen
Mar 1, 1988·Journal of the Neurological Sciences·K J ReinikainenP J Riekkinen
Aug 1, 1988·Brain : a Journal of Neurology·S L LoweD M Bowen
Jun 20, 1985·Nature·R E HammerR L Brinster
Jan 1, 1994·Brain Pathology·A AguzziS Isenmann
Aug 15, 1995·Biological Psychiatry·M HeiligA Wallin
Mar 7, 1996·Nature·K H CampbellI Wilmut
Nov 24, 1999·Archives of General Psychiatry·K L DavisV Haroutunian
Mar 5, 2002·Nature Biotechnology·Yifan DaiDavid L Ayares
Mar 5, 2002·Nature Medicine·Kellie L K TamashiroRandall R Sakai
Sep 3, 2002·Proceedings of the National Academy of Sciences of the United States of America·Simona CapsoniAntonino Cattaneo
Oct 3, 2002·Molecular and Cellular Neurosciences·Simona CapsoniAntonino Cattaneo
Oct 25, 2003·Nucleic Acids Research·Frank CzaudernaJörg Kaufmann
Dec 9, 2003·Journal of Neuroscience Methods·Cristina BäckmanAndreas C Tomac
Feb 28, 2004·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Joseph M Alisky, Beverly L Davidson
May 13, 2004·American Journal of Physiology. Endocrinology and Metabolism·S A StanleyS R Bloom
Jun 25, 2004·American Journal of Alzheimer's Disease and Other Dementias·Simona CapsoniAntonino Cattaneo
Oct 29, 2004·The American Journal of Pathology·Hung-Shu ChangWinston C Y Yu
Jan 25, 2005·Neuroscience Letters·Francisco Javier Gil-BeaMaría Javier Ramírez
Feb 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·Roberta De RosaAntonino Cattaneo
May 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Susanne E la FleurAditi Bhargava
Sep 30, 2005·International Psychogeriatrics·Jenny A Court, Elaine K Perry

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Citations

Aug 20, 2008·The American Journal of Chinese Medicine·Yan-Qiu LiuZheng-Tao Wang
Dec 23, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Samuel-Datum MoscavitchYehuda Shoenfeld
Jan 19, 2012·Cochlear Implants International·Martin DurisinJuergen Neuburger

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