Research Interests
Current research in Dr. Pappas’s laboratory focuses on animal models of disorders of brain development and aging. Behavioral, neurochemical and histopathological analyses are used to characterize rats treated with selective neurotoxins such as 192 IgG-saporin to lesion neurochemical systems shortly after birth. These rats may be a useful model for humans with Rett and Down syndrome, both of which show dysgenesis of cholinergic neurons. As well, they may be appropriate to study Alzheimer’s, since this disease of aging is associated with a loss of cholinergic neurons. A second line of research is the effects of chronic low grade ischemia, produced in the aging rat by bilateral ligation of the common carotids. In Alzheimer’s disease, there is reduced local cerebral blood flow which could initiate a cascade of events culminating in neural death and dementia. The carotid-ligated rats show an unusually late-developing memory impairment, loss of pyramidal cells in hippocampal CA1 and reactive gliosis there. The hippocampal cell death appears to be due to a remarkably late-appearing programmed cell death (apoptosis). Immunohistochemical and molecular neurobiological techniques are being used to trace the time course and mechanism of neural death and the ensuing memory impairment. The research described is supported by NSERC, Ontario Heart and Stroke Foundation and the Alzheimer’s Association (USA).
Publications
Pappas BA, Nguyen T, Brownlee B, Tanasoui D, Fortin F, Sherren N. Combined neonatal forebrain 192 IgG-saporin induced acetylcholine and 6-hydroxydopamine induced norepinephrine lesions. Brain Research, 2000, 867, 90-99.
Bennett SAL, Pappas BA, Stevens WD, Davidson CM, Fortin T, Chen J. Aberrent cleavage of amyloid precursor protein elicited by chronic cerebral hypoperfusion. Neurobiology of Aging, 2000, 21, 207-214.
Pappas, BA, Bayley PJ, Bui BK, Hansen LA, Thal LJ. Choline acetyltransferase activity and cognitive domain scores of Alzheimer’s patients. Neurobiology of Aging, 2000, 21, 11-17.
Davidson CM, Pappas BA, Stevens WD, Fortin T, Bennett SAL. Chronic cerebral hypoperfusion: loss of pupillary reflex, visual impairment and retinal neurodegeneration. Brain Research, 2000, 859, 96-103.
Sherren N, Pappas BA, Fortin T. Neural and behavioral effects of intracranial 192 IgG-saporin in neonatal rats: sexually dimorphic effects? Developmental Brain Research, 1999, 114, 49-62.
Bennett, SA, Chen J, Pappas BA, Roberts DC, Tenniswood M. Platelet activating factor receptor expression is associated with neuronal apoptosis in an in vivo model of excitotoxicity. Cell Death and Differentiation, 1998, 10, 867-75.
Pappas BA, Murtha SM, Park GAS, Hewitt K, Jordan S. Neurobehavioral evaluation of rats that chronically ingested Great Lakes chinook salmon. Regulatory Toxicology, 1998, 27, S55-S67.
Seegal R, Park GAS, Pappas, BA. Neurochemical evaluation of rats that chronically ingested Great Lakes chinook salmon. Regulatory Toxicology, 1998, 27, S68-S75.
Bennett SAL., Chen J-H, Tenniswood M., Davidson CM, Keyes, M, Fortin T, Pappas BA. Chronic reduction of cerebral blood flow elicits hippocampal neuronal apoptosis correlated with behavioral impairment. Neuroreport, 1998, 9, 161-6.
de la Torre JC, Nelson N, Sutherland RJ, Pappas BA. Reversal of ischemic-induced chronic memory dysfunction in aging rats with a free radical scavenger-glycolytic intermediate combination. Brain Research 1998, 779, 285-8.
Pappas BA, Davidson CM, Bennett SAL, de la Torre, JC, Fortin, T, Tenniswood, MPR. Chronic ischemia: memory impairment and neural pathology in the rat. Annals of the New York Academy of Science. 1997 826 498-501.
Mohr E, Nair NP, Sampson M, Murtha S, Belanger G, Pappas BA, Mendis, T. Treatment of Alzheimer’s disease with sabeluzole: functional and structural correlates. Clinical Neuropharmacology, 1997 20 338- 45.
Pappas BA, Zhang D, Davidson CM, Crowder T, Park GAS, Fortin T. Perinatal manganese exposure: behavioral, neurochemical and histopathological effects in the rat. Neurotoxicology and Teratology, 1997 19 17-25.
Pappas BA, Davidson CM, Fortin T, Nallathamby S, Park GAS, Mohr E, Wiley RG. 192 IgG-saporin lesion of basal forebrain cholinergic neurons in neonatal rats. Developmental Brain Research, 1996 9652-61.
Pappas BA, de la Torre JC., Davidson CM, Keyes MT, Fortin T. Chronic reduction of cerebral blood flow in the adult rat: late appearing CA1 cell loss and memory dysfunction. Brain Research, 1996 708 50-58.