Age‐associated synapse elimination in mouse parasympathetic ganglia

Coggan, Jay S.; Grutzendler, Jaime; Bishop, Derron L.; Cook, Melissa; Gan, Wen‐Biao; Heym, Jason; Lichtman, Jeff W.

doi:10.1002/neu.20022

Cited by 18 publications

(18 citation statements)

References 53 publications

(73 reference statements)

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“…In age-associated synapse elimination without pre and post synaptic death, there is a loss of synaptic input in cells, and in such cases in aged individuals there is an attenuation of EPSP amplitude together with an attenuation of both the amplitude and frequency of miniature excitatory postsynaptic potentials (Coggen et al 2004). …”

Section: Structural Changes In Synapses and Neurotransmitter Sensitivmentioning

confidence: 98%

A metabolic and functional overview of brain aging linked to neurological disorders

et al. 2009

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Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer's disease and Parkinson's disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.

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Section: Structural Changes In Synapses and Neurotransmitter Sensitivmentioning

confidence: 98%

A metabolic and functional overview of brain aging linked to neurological disorders

et al. 2009

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“…In the central nervous system (CNS), current views suggest that loss of neuronal connections rather than loss of neurons may be the major cause of age-related functional decline (Rapp and Gallagher, 1996; Scheff and Price, 2003; Rattner and Nathans, 2006; Morrison and Hof, 2007). In the peripheral nervous system (PNS), age-related loss of both synapses and neurons contribute to this functional decline (Coggan et al, 2004; Ohlemiller, 2006; Thrasivoulou et al, 2006). It is unclear, however, whether age-related synaptic change is the cause or simply an associated manifestation of neuronal loss in the PNS.…”

Section: Introductionmentioning

confidence: 99%

Age-related neuronal loss in the cochlea is not delayed by synaptic modulation

Jin

Ohlemiller

Lei

et al. 2011

Neurobiology of Aging

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Age-related synaptic change is associated with the functional decline of the nervous system. It is unknown whether this synaptic change is the cause or the consequence of neuronal cell loss. We have addressed this question by examining mice genetically engineered to over-or under-express neuregulin-1 (NRG1), a direct modulator of synaptic transmission. Transgenic mice overexpressing NRG1 in spiral ganglion neurons (SGNs) showed improvements in hearing thresholds, whereas NRG1 −/+ mice show a complementary worsening of thresholds. However, no significant change in age-related loss of SGNs in either NRG1 −/+ mice or mice over-expressing NRG1 was observed, while a negative association between NRG1 expression level and survival of inner hair cells during aging was observed. Subsequent studies provided evidence that modulating NRG1 levels changes synaptic transmission between SGNs and hair cells. One of the most dramatic examples of this was the reversal of lower hearing thresholds by "turning-off" NRG1 overexpression. These data demonstrate for the first time that synaptic modulation is unable to prevent age-related neuronal loss in the cochlea.

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“…The number of synapses in the nervous system changes under the influence of a variety of normal physiological factors, including hormonal status (Kretz et al, 2004), activity Harris et al, 2003), or age (Gan et al, 2003;Rosenzweig and Barnes, 2003;Coggan et al, 2004). Also, cognitive deficits associated with aging or certain pathologies result from widespread synapse loss in brain neurons (Spires and Hyman, 2004).…”

Section: Introductionmentioning

confidence: 99%

Age-Independent Synaptogenesis by Phosphoinositide 3 Kinase

Martín-Peña¹,

Acebes²,

Rodríguez³

et al. 2006

J. Neurosci.

100

118

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Synapses are specialized communication points between neurons, and their number is a major determinant of cognitive abilities. These dynamic structures undergo developmental-and activity-dependent changes. During brain aging and certain diseases, synapses are gradually lost, causing mental decline. It is, thus, critical to identify the molecular mechanisms controlling synapse number. We show here that the levels of phosphoinositide 3 kinase (PI3K) regulate synapse number in both Drosophila larval motor neurons and adult brain projection neurons. The supernumerary synapses induced by PI3K overexpression are functional and elicit changes in behavior. Remarkably, PI3K activation induces synaptogenesis in aged adult neurons as well. We demonstrate that persistent PI3K activity is necessary for synapse maintenance. We also report that PI3K controls the expression and localization of synaptic markers in human neuroblastoma cells, suggesting that PI3K synaptogenic activity is conserved in humans. Thus, we propose that PI3K stimulation can be applied to prevent or delay synapse loss in normal aging and in neurological disorders.

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Age‐associated synapse elimination in mouse parasympathetic ganglia

Cited by 18 publications

References 53 publications

A metabolic and functional overview of brain aging linked to neurological disorders

A metabolic and functional overview of brain aging linked to neurological disorders

Age-related neuronal loss in the cochlea is not delayed by synaptic modulation

Age-Independent Synaptogenesis by Phosphoinositide 3 Kinase

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