The overall objective of this proposal is to gain a better understanding of the organization of somatostatin (SOM) containing neurons in areas of the non-human primate hippocampal formation, a set of structures though to be homologous with regions of the human limbic cortex that are profoundly affected in Alzheimer's disease. Our experimental hypothesis is that hippocampal formation neurons containing SOM, a putative neurotransmitter known to decline in AD, may occupy a pivotal position in cortical and limbic neural circuitry, so that their deterioration would contribute to the phenomena of cortical and hippocampal disconnection in AD. The specific goals of this proposal will determine the distribution of SOM neurons in the hippocampal formation, whether these SOM containing neurons exhibit features of local circuit neurons, whether they are located predominantly in cortical layers containing long projection neurons, whether SOM neurons serve as interneurons or projection neurons of both, whether the laminar organization of SOM immunoreactive fibers matches the distribution of SOM receptors, and whether SOM neurons exhibit age-related changes in the hippocampal formation. The planned studies will utilize immunohistochemistry using SOM poly clonal antibodies, NADPH-histochemistry, horseradish peroxidase retrograde tracer histochemistry combined with SOM immunohistochemistry, receptor autoradiography and computer assisted morphometric analysis of SOM neurons. Anatomical studies of the neural circuitry of non-human primate cortical regions homologous to areas affected in AD have provided basic information needed to better understand the meaning of the cortical distribution of plaques and tangles seen in AD. The information gathered from this proposal will ad to our knowledge or cortical circuitry and will provide new data relevant to neurological disorders and mental health.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026146-02
Application #
3411821
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1988-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Sun Health Research Institute
Department
Type
DUNS #
City
Sun City
State
AZ
Country
United States
Zip Code
85351
Brady, D R; Mufson, E J (1997) Parvalbumin-immunoreactive neurons in the hippocampal formation of Alzheimer's diseased brain. Neuroscience 80:1113-25
Brady, D R; Carey, R G; Mufson, E J (1992) Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) profiles in the amygdala of human and New World monkey (Saimiri sciureus). Brain Res 577:236-48
Gomez-Ramos, P; Mufson, E J; Moran, M A (1992) Ultrastructural localization of acetylcholinesterase in neurofibrillary tangles, neuropil threads and senile plaques in aged and Alzheimer's brain. Brain Res 569:229-37
Mufson, E J; Kordower, J H (1992) Cortical neurons express nerve growth factor receptors in advanced age and Alzheimer disease. Proc Natl Acad Sci U S A 89:569-73
Kordower, J H; Le, H K; Mufson, E J (1992) Galanin immunoreactivity in the primate central nervous system. J Comp Neurol 319:479-500
Mufson, E J; Higgins, G A; Kordower, J H (1991) Nerve growth factor receptor immunoreactivity in the new world monkey (Cebus apella) and human cerebellum. J Comp Neurol 308:555-75
Brady, D R; Mufson, E J (1991) Alz-50 immunoreactive neuropil differentiates hippocampal complex subfields in Alzheimer's disease. J Comp Neurol 305:489-507
Mufson, E J; Presley, L N; Kordower, J H (1991) Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson's disease: reduced cell numbers and co-localization with cholinergic neurons. Brain Res 539:19-30
Mufson, E J; Brady, D R; Carey, R G (1990) Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry in the hippocampal formation of the New World monkey (Saimiri sciureus). Brain Res 516:237-47
Kordower, J H; Mufson, E J (1990) Galanin-like immunoreactivity within the primate basal forebrain: differential staining patterns between humans and monkeys. J Comp Neurol 294:281-92

Showing the most recent 10 out of 14 publications