Age-related changes in expression of ampa-selective glutamate receptor subunits: Is calcium-permeability altered in hippocampal neurons?

Pagliusi, Sonia; Gerrard, Philip; Abdallah, Mheni Ben; Talabot, Dominique; Catsicas, Stefan

doi:10.1016/0306-4522(94)90422-7

Cited by 70 publications

(24 citation statements)

References 26 publications

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“…Data from the hippocampus raise the possibility that excitotoxic loss of GluR1-intense interneurons may contribute to the aging process (Pagliusi et al, 1994). Selective injury to cortical GABAergic neurons plays a role in several models of epilepsy (see, e.g., Rib& et al, 1982;House et al, 1986;Mittmann et al, 1994); these neurons have been shown to resist N-methyl-D-aspartate (NMDA)-mediated excitotoxicity (Tecoma and Choi, 19891, but the present data suggest the possible selective vulnerability of GluR1-intense GABAergic neurons to damage via calcium influx through AMPA receptors.…”

Section: Glur1-positive Interneurons: Functional Implicationsmentioning

confidence: 98%

GluR1-immunopositive interneurons in rat neocortex

1996

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Recent in vitro studies suggest that inhibitory interneurons in cortex may express the GluR1 glutamate receptor subunit in the absence of GluR2, leading to calcium-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) channels. We performed a study of rat somatic sensory cortex to confirm and extend these observations, using quantitative immunocytochemistry for multiple antigens. A morphologically distinct subpopulation of nonpyramidal neurons in neocortex was intensely immunoreactive for GluR1. Electron microscopic analysis of these cells revealed somatic staining for GluR1, mainly in the rough endoplasmic reticulum. Dendritic staining was concentrated at the synaptic active zone and in the adjacent subsynaptic cytoplasm. Double immunostaining revealed that the large majority of intensely GluR1-positive cells contained gamma-aminobutyric acid or its synthetic enzyme, glutamic acid decarboxylase, but little or no GluR2. Thus, AMPA receptors on a subpopulation of inhibitory interneurons in cortex are likely to be calcium permeable. This calcium permeability is likely to influence functional properties of these neurons; it may underlie the high levels of calcium-binding proteins they contain; and may render them liable to excitotoxic injury

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Section: Glur1-positive Interneurons: Functional Implicationsmentioning

confidence: 98%

GluR1-immunopositive interneurons in rat neocortex

1996

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“…AMPA receptor densities were reported either increased, unchanged or reduced in rat hippocampal sub®elds (Miyoshi et al, 1991;Le Jeune et al, 1996;Nicolle et al, 1996). Importantly, age-related changes in expression of AMPA receptor subunits in the hippocampus and basal forebrain may have detrimental consequences for neuronal vulnerability due to altered Ca 2 permeability (Pagliusi et al, 1994;Akaike and Rhee, 1997). Overall, evidence on the behavioural consequences of glutamatergic receptor imbalances is patchy and inconsistent.…”

Section: Ageing and Neuronal Plasticitymentioning

confidence: 98%

A unifying hypothesis of Alzheimer's disease. I. Ageing sets the stage

Heininger

1999

Hum. Psychopharmacol. Clin. Exp.

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In a series of ®ve papers, evidence from neurobiology, endocrinology and immunology is integrated into a holistic, coherent hypothesis accommodating genetic, medical and environmental risk factors into a cascade of pathophysiological events that leads to the clinical manifestation of Alzheimer's disease (AD). The perturbation of the calcium-energy-oxidative stress triangle emerges as pathophysiological leitmotif of ageing and AD. Cellular Ca 2 homeostasis and energy metabolism are closely interdependent. Ca 2 ions regulate the activity of a variety of ratelimiting enzymes of the tricarboxylic acid cycle and respiratory chain. Under physiological circumstances, the supply of energy according to demand is regulated by Ca 2 cycling across mitochondrial membranes. In certain pathological conditions, Ca 2 uncouples electron transfer and oxidative phosphorylation and increases the mitochondrial production of oxygen radicals which in tandem with Ca 2 precipitate the breakdown of mitochondrial function and structure. As most important risk factor, ageing sets the stage for the development of AD. The delicate regulation of the neuroendocrine network which physiologically modulates the Ca 2 -energy-redox homeostasis, deteriorates in ageing, compromising the hormonal balance between neurotrophic/protective and neuroaggressive factors. Thus, levels and/or signal transduction pathways of neurotrophic-factors such as neuropeptide Y, neurotrophins, DHEA/ DHEAS, gonadal hormones, melatonin, insulin, insulin-like growth factors, somatostatin, thyroid hormones, and substance P decay, paralleled by the compromise of the hypothalmic-pituitary-adrenal (HPA)-axis feedback inhibition leading to a hyperresponsiveness to stress and a loss of diurnal rhythm of secretion of neuroaggressive glucocorticoids. Both add up to disrupt Ca 2 and energy homeostasis, put the nerve cells under metabolic and oxidative stress and lead to a compromise of neuronal excitability, signal transduction processes and neuronal plasticity. Subject to the same endocrinological dysregulation, the ageing immune system exhibits a primitive response pattern with impairment of speci®c cellular and activation of unspeci®c humoral and microglial immune responses. Thus, the ageing-related concerted perturbation of the homeostatic control in the neuroendocrinoimmunological network creates phenomena which in many aspects are qualitatively similar to changes in AD and lay the foundations for the development of the disease.

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“…Developmental changes in GluR4 subunit expression have been observed in the hippocampus, cerebellum and cortex, however, no differences in GluR4 expression were observed in the basal ganglia throughout development. This variation in AMPA receptor subunit expression with age may be implicated in the establishment and regulation of synaptogenesis [55 -57] and excitotoxicity [58,59]. LTP, which refers to a long lasting increase in synaptic transmission, has been explained by a net increase in the probability of neurotransmitter release [60,61].…”

Section: Ampa Receptors and Ageingmentioning

confidence: 99%

AMPA Receptors: potential implications in development and disease

Franciosi¹

2001

CMLS, Cell. Mol. Life Sci.

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Alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptors are one type of ionotropic glutamate receptor involved in rapid excitatory synaptic transmission. AMPA receptors have been increasingly implicated in long-term potentiation, and recent evidence suggests that they may play a role in disorders affecting the nervous system. The finding that early in postnatal development AMPA receptors are not expressed has lately been the focus of much attention. Resolving the factors involved in AMPA receptor expression suggests that their induction is a developmentally regulated process with the possibility that alterations in receptor expression may be correlated with pathology in neurological disorders. This paper provides an overview of factors involved in AMPA receptor induction as well as of their role in plasticity and neuronal pathologies.

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Age-related changes in expression of ampa-selective glutamate receptor subunits: Is calcium-permeability altered in hippocampal neurons?

Cited by 70 publications

References 26 publications

GluR1-immunopositive interneurons in rat neocortex

GluR1-immunopositive interneurons in rat neocortex

A unifying hypothesis of Alzheimer's disease. I. Ageing sets the stage

AMPA Receptors: potential implications in development and disease

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