Neuronal Plasticity and Responsiveness During the Aging Process
Our research emphasizes the analysis of biochemical and molecular events
that occur in specific mammalian neural systems which specify the unique neurochemical and
morphological compensatory responses of these systems to stress, insult or injury. The
work in this laboratory 
is derived from our continuing interest in understanding the mechanisms
underlying the neurochemical changes seen in neurodegenerative diseases and affective
disorders. While neuronal systems retain a remarkable degree of adaptability during the
aging process, age-related deficits in behavioral responsiveness associated with specific
neural systems suggests that the ability of these systems to respond to stimulation,
stress or insult is reduced. We hypothesize that similar changes in neuronal plasticity
play a role in the etiology of affective disorders.
This lab focuses its analyses on the noradrenergic locus coeruleus system, using it as a model to study neuronal plasticity in response to stress, injury and insult in both young and aging animal models. We have recently demonstrated that the robust ability of this system to compensate for neuronal insult in young rats is attenuated in the aged animal. We are actively engaged in evaluating the molecular factors that are either intrinsic to locus coeruleus neurons (e.g. signal transduction capacity) or extrinsic to these neurons (e.g. expression of trophic factors) that are functionally related to this age-related deficit as a way to define the mechanisms that underlie the neurochemical and morphological deficits associated with neurodegenerative and affective disorders.
Selected References
Wang, X.-T., Unnerstall, J.R., Ibuki, T., Wang, H. and Pappas, G.D. (2000) Comparison of tyrosine hydroxylase and preproenkephalin expression in rat adrenal medullary explants in vitro and transplanted into subarachnoid space. Exp. Neurol. 161:346-360.
Rachman, I.M., Unnerstall, J.R., Pfaff, D.W. and Cohen, R.S. (1998) Estrogen alters behavior and forebrain c-fos expression in ovariectomized rats subjected to the forced swim test. Proc. Nat'l. Acad. Sci. USA 95:13941-13946.
Rachman, I.M., Unnerstall, J.R., Pfaff, D.W. and Cohen, R.S. (1998) Regulation of neuronal nitric oxide synthase mRNA in lordosis-relevant neurons of the ventromedial hypothalamus following short-term estrogen treatment. Mol. Brain Res. 59:105-108.
Wang, X.-T., Pappas, G.D., Sagen, J. and Unnerstall, J.R. (1996) Cells expressing preproenkephalin mRNA in the rat pineal gland are not serotonin-producing pinealocytes: Evidence using in situ hybridization combined with immunohistochemistry for serotonin. Cell. Mol.Neurobiol. 16:73-84.
Unnerstall, J.R. and Long, M.M. (1996) Differential effects of the intraventricular administration of 6-hydroxydopamine on the induction of Type II -tubulin and tyrosine hydroxylase mRNA in the locus coeruleus of the aging Fischer 344 rat. J. Comp. Neurol.364:363-381.
Yu, H.-J., Unnerstall, J.R. and Green, R.D. (1995) Determination and cellular localization of adenylyl cyclase isozymes expressed in embryonic chick heart. FEBS Letters 374:89-94,.
Hama, A.T., Unnerstall, J.R., Siegan, J.B. and Sagen, J. (1995) Modulation of NMDA receptor expression in the rat spinal cord by peripheral nerve injury and adrenal medullary grafting. Brain Res. 687:103-113.
Unnerstall, J.R. and Ladner, A. (1994) Deficits in the activation and phosphorylation of hippocampal tyrosine hydroxylase in the aged Fischer 344 rat following intraventricular administration of 6-hyroxydopamine. J. Neurochem. 62:280-290.