The Basic Biology of Aging at the University of Washington
Daniel Storm, Ph.D.

Biosketch Information
Email: dstorm@u.washington.edu

It is our hypothesis that the decline in the type I adenylyl cyclase in the hippocampus may contribute to memory loss and melatonin loss associated with aging. We hypothesize also that type one adenylyl cyclase (AC1) in the pineal gland is the source of cAMP used to drive the synthesis of nocturnal melatonin synthesis. AC1 is developmentally expressed with maximal expression in young mice with levels falling off with aging. We have made a transgenic mouse strain that overexpresses AC1 in an attempt to over-ride the aging-related decrease in melatonin expression.

To test this hypothesis we are using several adenylyl cyclase mutant mouse strains that we have produced to examine the role of the cAMP signal transduction system for aging-related decreases in melatonin production. Our transgenic mouse will also be used to study the role of AC1 in spatial memory loss that occurs in aging mice.

Dr. Storm has been Professor of Pharmacology since 1982. He has served on the NIH Cell Physiology Study Section and won the NIH Javits Neuroscience Award.

Selected Relevant Publications
Baker LP, Nielsen M, Impey S, Metcalf MA, Poser SW, Chan G, Obrietan K, Hamblin MW, Storm DR. Stimulation of AC1 and AC8 by the Gs-coupled 5-HT subtype 5-HT7A receptor. J Biol Chem 273:17469-17476, 1998.

AbdelMajidl RM, Leong WL, Schalkwyk LC, Smallman DS, Wong ST, Storm DR, Fine A, Dobson DL, Neuroman PE. Loss of AC1 activity disrupts patterning of mouse somatosensory cortex. Nat Genet 19:289-291, 1998.

Storm DR, Hansel C, Hacker B, Parent A, Linden DJ. Impaired cerebellar LTP in AC1 mutant mice. Neuron 20:1199-1210, 1998.

Baker LP, Nielsen MD, Impey S, Hacker BM, Poser SW, Chan M, Storm DR. Regulation and immunohistochemical localization of beta/gamma-stimulated ACs in mouse hippocampus. J Neurosci 19:180-192, 1999.

Thome J, Sakai N, Shin KH, Steffen C, Zhang YJ, Impey S, Storm DR, Duman RS. Chronic antidepressant treatment induces CRE-mediated gene transciption. J Neurosci 20:4030-4036, 2000.

Schaefer ML, Wong ST, Wozniak DF, Muglia LM, Liauw JA, Nardi A, Hartman RE, Vogt SH, Luedke CE, Storm DR, Muglia LJ. Altered stress-induced anxiety in AC deficient mice. J Neurosci 20:4809-4820, 2000.

Poser S, Impey S, Trinh K, Xia Z, Storm DR. SRF-dependent gene expression is required for mitogen- induced proliferation through a PI3 kinase signal transduction cascade. EMBO J 15:4955-4966, 2000.

Watt W, Storm DR. Odorants stimulate the Erk/MAP kinase pathway and activate CRE-mediated transcription in olfactory sensory neurons. J Biol Chem 276: 2047-2052, 2001.

Chan GCK, Lernmark U, Xia Z, Storm DR. DNA elements of the type I adenylyl cyclase gene locus enhance reporter gene expression in neurons and pinealocytes. Euro J Neurobiol 13:2054-2066, 2001.

Shaw-Lutchman TZ, Barrot M, Wallace T, Gilden L, Zachariou V, Impey S, Duman RS, Storm DR, Nestler EJ. Regional and cellular mapping of CRE-mediated transcription during naltrexone-precipitated morphine withdrawal. J Neurosci, in press.