Influence of age on epidermal growth factor receptor level in the rat brain

Hiramatsu, Masahiko; Kashimata, Masanori; Sato, Akinao; Murayama, Makoto; Minami, Naomi

doi:10.1007/bf01960230

Cited by 28 publications

(8 citation statements)

References 14 publications

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“…In AD pathology, aggregates and deposits of the protein fragment β -amyloid (plaques) and twisted strands of the protein Tau (neurofibrillary tangles) induce the generation of nerve cell damage and cell death in areas of the brain including the cortex and especially the hippocampus [110, 112–114]. With respect to an association with AD etiology it has been demonstrated that EGFR expression in the rat brain reduces with age both in males and females [115]. AD-related neuritic plaques observed in the cerebral cortex and hippocampus of patients with AD also immunostain positively for EGFR [93].…”

Section: Egfr and Neurodegenerative Diseasementioning

confidence: 99%

Central Role of the EGF Receptor in Neurometabolic Aging

Siddiqui

Fang

et al. 2012

International Journal of Endocrinology

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A strong connection between neuronal and metabolic health has been revealed in recent years. It appears that both normal and pathophysiological aging, as well as neurodegenerative disorders, are all profoundly influenced by this “neurometabolic” interface, that is, communication between the brain and metabolic organs. An important aspect of this “neurometabolic” axis that needs to be investigated involves an elucidation of molecular factors that knit these two functional signaling domains, neuronal and metabolic, together. This paper attempts to identify and discuss a potential keystone signaling factor in this “neurometabolic” axis, that is, the epidermal growth factor receptor (EGFR). The EGFR has been previously demonstrated to act as a signaling nexus for many ligand signaling modalities and cellular stressors, for example, radiation and oxidative radicals, linked to aging and degeneration. The EGFR is expressed in a wide variety of cells/tissues that pertain to the coordinated regulation of neurometabolic activity. EGFR signaling has been highlighted directly or indirectly in a spectrum of neurometabolic conditions, for example, metabolic syndrome, diabetes, Alzheimer's disease, cancer, and cardiorespiratory function. Understanding the positioning of the EGFR within the neurometabolic domain will enhance our appreciation of the ability of this receptor system to underpin highly complex physiological paradigms such as aging and neurodegeneration.

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Section: Egfr and Neurodegenerative Diseasementioning

confidence: 99%

Central Role of the EGF Receptor in Neurometabolic Aging

Siddiqui

Fang

et al. 2012

International Journal of Endocrinology

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“…Beginning at 15 days after birth, it can be detected in the globus pallidus, endopeduncular nucleus, substantia nigra pars reticulata, ventral pallidum, islands of Calleja complex, and to a lesser extent in the stria terminalis and layers I-V of cerebral cortex of rats (Fallon et al, 1984). The EGF receptor, which also binds transforming growth factor-a (TGF-a) (Marquardt et al, 1983) is also present in mammalian brain (Adamson and Meek, 1984;Gomez-Pinilla et al, 1988;Heldin et al, 1979;Hiramatsu et al, 1988;Leutz and Schachner, 1982;Sadiq et al, 1985;Simpson et al, 1982;Werner et al, 1988). Studies have shown the EGF receptor to be present on glia (Heldin et al, 1979;Simpson et al, 1982;Leutz and Schachner, 1981;Nieto-Sampedro and Broderick, 1989), neurons (Werner et al, 1988), or both (Gomez-Pinilla et al, 1988;Leutz and Schachner, 1982;Wang et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

EGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture

Casper

Mytilineou

Blum

1991

J of Neuroscience Research

176

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Epidermal growth factor (EGF) immunoreactive material has been demonstrated to be present in the basal ganglia. In this study, we investigated the effect of EGF on cells cultured from 16-day embryonic rat mesencephalon, which included dopamine neurons that project to the striatum in vivo. EGF receptors were detected in untreated cultures by [125I]-EGF binding. Treatment of the cultures with EGF resulted in up to 50-fold increases in neuronal high-affinity dopamine uptake. Scatchard analysis of uptake kinetics and counting of tyrosine hydroxylase-immunoreactive cells suggest that the effect of EGF on uptake is due to increased survival and maturation of dopaminergic neurons. By contrast, the high-affinity uptake for serotonin was increased only threefold over its controls. There was no significant effect on high-affinity gamma-aminobutyric acid (GABA) uptake. These results suggest that EGF is acting as a neurotrophic agent preferential for dopaminergic neurons in E16 mesencephalic cultures. Immunocytochemistry for glial fibrillary acidic protein demonstrated an increase in astroglia with EGF treatment. Fluorodeoxyuridine, an agent that is toxic to proliferating cells was able to eliminate the effect of EGF on dopamine uptake, suggesting that EGF may be increasing dopaminergic cell survival largely through a population of dividing cells.

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“…There are several reports suggesting that bFGF promotes the survival of mesencephalic DA neurons. Hiramatsu and co-workers (Hiramatsu et al, 1988) reported a gradual decrease in the number of brain EGFR sites in rats during normal aging, although the authors did not determine if the difference was associated with any CNS dysfunction or with the presence of any marker degeneration. EGF receptor (EGFR) binding sites have been found in rodent and human brain (Nexo et al, 1980;Adamson et al, 1981;Sagen and Pappas, 1987;Hiramatsu et al, 1988), and in cells of human brain tumors (Reubi et al, 1989).…”

Section: Types Of Nfs and Their Target Cellsmentioning

confidence: 98%

“…Moreover, additive effects of the two factors cannot be completely excluded (Araujo et al, 1990). EGF receptor (EGFR) binding sites have been found in rodent and human brain (Nexo et al, 1980;Adamson et al, 1981;Sagen and Pappas, 1987;Hiramatsu et al, 1988), and in cells of human brain tumors (Reubi et al, 1989). On the other hand, it is thought that the effects of bFGF are indirect, requiring the presence of glial cells (Ferrari et al, 1989;Knusel et al, 1990), although this data are still controversial ( Walicke and Baird, 1988;Hefti et al, 1989).…”

Section: Types Of Nfs and Their Target Cellsmentioning

confidence: 99%

Neurotrophic factors for the investigation and treatment of movement disorders

2003

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Neurotrophic factors (NFs) are proteins that enhance neuronal survival, differentiation, neurotransmitter function and resistance to neurotoxins and lesions. For these reasons the NFs are considered as a new potential therapeutic tool for the treatment of neurodegenerative disorders, a group of diseases that produce the most important cause for disability in the Western world. Some NFs prevent or even reverse the behavioral, biochemical, pharmacological and histological abnormalities observed in several in vitro and in vivo models of neurodegenerative disorders, namely Parkinson's disease. Several NFs have been investigated in primate models of neurological disorders and some of them have been used for patients with these diseases. The results so far obtained in humans have been disappointing for several reasons, including technical problems for delivery, unbearable side effects or lack of efficacy. Future approaches for the use of NFs in humans should include the following: (1) Investigation of the putative compounds in animal models more related to the pathophysiology of each disease, such as in genetic models of neurodegenerative diseases; (2) New methods of delivery including genetic engineering by viral vectors and administration through implantable devices; (3) More precise methods of continuous response evaluation, including the novel neuroimaging techniques; (4) Investigation of the effects of behavioral stimulation and conventional pharmacotherapy on the metabolism of NFs.

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Influence of age on epidermal growth factor receptor level in the rat brain

Cited by 28 publications

References 14 publications

Central Role of the EGF Receptor in Neurometabolic Aging

Central Role of the EGF Receptor in Neurometabolic Aging

EGF enhances the survival of dopamine neurons in rat embryonic mesencephalon primary cell culture

Neurotrophic factors for the investigation and treatment of movement disorders

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