D. Heyer

University of Rochester

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Christina L. Williams

Duke University

Warren H. Meck

Duke University

R. Loy

University of Rochester

Rebekah Loy

University of Rochester

Peter S. DiStefano

Zebra Biologics (United States)

Giulio Taglialatela

The University of Texas Medical Branch at Galveston

Luciano Angelucci

Istituto di Farmacologia Traslazionale

Margaret Clagett‐Dame

University of Wisconsin–Madison

Regino Perez‐Polo

The University of Texas Medical Branch at Galveston

Cooperative Institutions

University of Rochester Medical Center

The University of Texas Medical Branch at Galveston

Sigma Tau (Italy)

University of Rochester

University of California, San Diego

Duke University

Galveston College

Sapienza University of Rome

United States Department of Veterans Affairs

Monroe Community Hospital

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Choline-Induced Spatial Memory Facilitation Correlates with Altered Distribution and Morphology of Septal Neurons

Advances in experimental medicine and biology (1991)

Rebekah Loy D. Heyer Christina L. Williams Warren H. Meck

Nucleus basalis

Neocortex

Entorhinal cortex

10.1007/978-1-4757-0145-6_21

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Citations (101)

Regional CNS uptake of blood‐borne nerve growth factor

Journal of Neuroscience Research (1994)

R. Loy Giulio Taglialatela Luciano Angelucci D. Heyer Regino Perez‐Polo

Nerve growth factor (NGF), in addition to being a neurotrophic substance, has effects on the endocrine and immune systems. For example, intravenous injection of NGF results in a cascade of events leading to an increase in glucocorticoid secretion. While this response appears to be mediated centrally, there has been no evidence that circulating NGF has access to the CNS. Using intravenous injections of 125I-NGF, we find specific uptake at 1 hr but none at 6 hr, into homogenates of the basal forebrain, cerebellum, frontal cortex, hippocampus, and olfactory bulb. By autoradiography, uptake is localized to circumventricular organs, deep layers of the cerebellum, and all layers of the hippocampal region CA1, but not the dentate gyrus. Thus, uptake of blood-borne NGF could affect the hypothalamic-pituitary-adrenal axis via binding to NGF receptors present in the hippocampus. However, the sources of endogenous NGF, the mechanism of access through the blood-brain barrier, the eventual fate of NGF entering from the blood, and the physiological significance of this uptake remain to be elucidated.

Circumventricular organs

Median eminence

10.1002/jnr.490390311

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Localization of NGF receptors in normal and Alzheimer's basal forebrain with monoclonal antibodies against the truncated form of the receptor

Journal of Neuroscience Research (1990)

R. Loy D. Heyer Margaret Clagett‐Dame Peter S. DiStefano

Abstract Four new monoclonal antibodies to the extracellular domain of the nerve growth factor receptor (NGFR) have been evaluated for their specificity to NGFR and their utility in localizing NGFR in human brain. All four antibodies, as well as Me20.4, show similar cellular localization and patterns of immunoreactivity in basal forebrain neurons. NGFR monoclonal antibody XIF1 stains optimally over the widest range of concentrations, with staining being reduced only slightly at less than 10 pg/ml or more than 100 ng/ml, and produces the lowest background of those tested. Staining with all NGFR monoclonal antibodies is blocked by the addition of as little as 5‐fold excess human recombinant truncated NGFR protein. The distribution of NGFR‐containing neurons is similar to that previously described in normal human fore‐brain, as is the reduction in cell size in nucleus basalis (Ch4am) in brains from patients with Alzheimer's disease. In addition, we find evidence in the two Alzheimer's cases examined for a previously unreported loss of cells in the horizontal limb nucleus of the diagonal band (Ch3) in Alzheimer's disease. The loss of these neurons, which in normal brain have characteristic varicose dendritic processes extending to the pial surface adjacent to the cisternal space, may indicate a change in the relationship of NGF‐sensitive neurons to the vasculature. Since these neurons project to olfactory bulb and cortex in rodent and primate brains, their loss may also reflect damage to the olfactory system in Alzheimer's disease.

Nucleus basalis

Perivascular space

Forebrain

Human brain

10.1002/jnr.490270426

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Citations (18)

Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in perinatally choline-supplemented rats

Brain Research (1998)

Christina L. Williams Warren H. Meck D. Heyer Rebekah Loy

The effects of choline supplementation during two time-frames of early development on radial-arm maze performance and the morphology of basal forebrain neurons immunoreactive for the P75 neurotrophin receptor (NTR) in male and female Sprague–Dawley rats were examined. In the first experiment, rats were supplemented with choline chloride from conception until weaning. At 80 days of age, subjects were trained once a day on a 12-arm radial maze for 30 days. Compared to control littermates, supplemented rats made fewer working and reference memory errors; however, the memory enhancing effects of choline supplementation were greater in males than females. A morphometric analysis of NTR-immunoreactive cell bodies at three levels through the medial septum/diagonal band (MS/DBv) of these rats revealed that perinatal choline supplementation caused the somata of cells in the MS/DBv to be larger by 8–15%. In a second experiment, choline supplementation was restricted to embryonic days 12–17. A developmental profile of NTR immunoreactive cell bodies in the MS/DBv of 0-, 8-, 16-, 30- and 90-day old male and female rats again revealed that cell bodies were larger in choline-supplemented rats than controls. As in the behavioral studies, the effect of choline supplementation was greater in male than female rats. These data are consistent with the hypothesis that supplementation with choline chloride during early development leads to an increase in the size of cell bodies of NTR-immunoreactive cells in the basal forebrain and that this change may contribute to long-term improvement in spatial memory.

Choline

Forebrain

Choline chloride

Basal (medicine)

10.1016/s0006-8993(98)00229-7

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Citations (142)