Phosphatidylserine increases acetylcholine release from cortical slices in aged rats

Pedata, Felicita; Giovannelli, Lisa; Spignoli, G.; Giovannini, Maria Grazia; Pepeu, Giancarlo

doi:10.1016/0197-4580(85)90013-2

Cited by 63 publications

(15 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This lecithin behaviour was justified by suggesting a mechanism involving ACh release stimulation [196]. ACh content and its release were increased by treatment with both phosphatidylserine [197] and CDP-choline [198,199]. The same results were obtained with choline alphoscerate [200].…”

Section: Choline Precursors and High-affinity Chtmentioning

confidence: 82%

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Amenta¹,

Tayebati

2008

CMC

119

View full text Add to dashboard Cite

Acetylcholine (ACh) is a neurotransmitter widely diffused in central, peripheral, autonomic and enteric nervous system. This paper has reviewed the main mechanisms of ACh synthesis, storage, and release. Presynaptic choline transport supports ACh production and release, and cholinergic terminals express a unique transporter critical for neurotransmitter release. Neurons cannot synthesize choline, which is ultimately derived from the diet and is delivered through the blood stream. ACh released from cholinergic synapses is hydrolyzed by acetylcholinesterase into choline and acetyl coenzyme A and almost 50% of choline derived from ACh hydrolysis is recovered by a high-affinity choline transporter. Parallel with the development of cholinergic hypothesis of geriatric memory dysfunction, cholinergic precursor loading strategy was tried for treating cognitive impairment occurring in Alzheimer's disease. Controlled clinical studies denied clinical usefulness of choline and lecithin (phosphatidylcholine), whereas for other phospholipids involved in choline biosynthetic pathways such as cytidine 5'-diphosphocholine (CDP-choline) or alpha-glyceryl-phosphorylcholine (choline alphoscerate) a modest improvement of cognitive dysfunction in adult-onset dementia disorders is documented. These inconsistencies have probably a metabolic explanation. Free choline administration increases brain choline availability but it does not increase ACh synthesis/or release. Cholinergic precursors to serve for ACh biosynthesis should be incorporate and stored into phospholipids in brain. It is probable that appropriate ACh precursors and other correlated molecules (natural or synthesized) could represent a tool for developing therapeutic strategies by revisiting and updating treatments/supplementations coming out from this therapeutic stalemate.

show abstract

Section: Choline Precursors and High-affinity Chtmentioning

confidence: 82%

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Amenta¹,

Tayebati

2008

CMC

119

View full text Add to dashboard Cite

show abstract

“…The fast Ca2+ entry is mediated mostly by voltage-dependent Ca2+ channels and involved in triggering neurotransmitter release (Augustine et al, 1987). The possibility has been suggested (Gibson and Peterson, 1987) that the reduction in the fast phase of voltage-dependent Ca2+ uptake, involving type L and N Ca2+ channels, may be responsible for the age-induced decrease in evoked neurotransmitter release from the brain, which has been demonstrated in both cortical synaptosornes (Meyer et al, 1984) and slices (Pedata et al, 1985). In this regard, it has been shown recently that the blockade of N type Ca2+ channels by w-conotoxin inhibits synaptic transmission (Kamiya et al, 1988) and a decrease in the number of cortical N type Ca2+ channels occurs in aging rats (Moresco et al, 1988).…”

Section: Discussionmentioning

confidence: 99%

Effect of Age on K⁺‐Induced Cytosolic Ca²⁺ Changes in Rat Cortical Synaptosomes

Giovannelli

Pepeu

1989

Journal of Neurochemistry

View full text Add to dashboard Cite

45Ca2+ uptake and cytosolic Ca2+ concentrations [( Ca2+]i) were measured in synaptosomes prepared from the cerebral cortex of 3-, 16-, and 24-month-old male Charles River Wistar rats. Electron-microscopic examination demonstrated no morphological differences between the synaptosomes prepared from 3- and 24-month-old rats. The fast phase of Ca2+ uptake was reduced in the 24-month-old animals as compared to the 3-month-old ones (-23%, p less than 0.001), whereas no difference was found between the 16- and the 3-month-old rats. Age did not modify [Ca2+]i, as measured by the quin 2 technique, both at rest and immediately after depolarization with 50 mM K+. The Ca2+ load following depolarization was cleared in about 13 min in the 3-month-old rats. The rate of clearance was significantly slower both in the 16- (p less than 0.01) and in the 24-month-old rats (p less than 0.0001). The addition of verapamil (60 microM) after depolarization restored [Ca2+]i to resting level in aged rats at the same rate as in young rats. A prolonged Ca2+ influx, therefore, may be responsible for the slower clearance of Ca2+ load in aged rats.

show abstract

“…Attempts to treat A D dementia by enhancing acetylcholine release have been made using phosphatidylserine and 4-aminopyridine (Table 1). Phosphatidylserine has been shown to increase acetylcholine release from rat cortical slices (13) by an as yet unknown mechanism, whereas 4-aminopyridine acts to block potassium channels, thus prolonging depolarisation and thereby increasing neurotransmitter release.…”

Section: Release Enhancersmentioning

confidence: 99%

Biochemical pathology and treatment strategies in Alzheimer's disease: Emphasis on the cholinergic system

Winblad

Messamore

O’Neill

et al. 2009

Acta Neurologica Scandinavica

View full text Add to dashboard Cite

The neurochemical pathology of Alzheimer's disease (AD) has been consistently shown to involve cholinergic degeneration in the cerebral cortex. This together with evidence from experimental animal studies showing that cholinergic neurones play a role in learning and memory processes has formed the basis of the cholinergic hypothesis of Alzheimer's dementia and the major rationale for neurotransmitter replacement therapy of the disorder.

show abstract

Phosphatidylserine increases acetylcholine release from cortical slices in aged rats

Cited by 63 publications

References 11 publications

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Effect of Age on K⁺‐Induced Cytosolic Ca²⁺ Changes in Rat Cortical Synaptosomes

Biochemical pathology and treatment strategies in Alzheimer's disease: Emphasis on the cholinergic system

Contact Info

Product

Resources

About

Phosphatidylserine increases acetylcholine release from cortical slices in aged rats

Cited by 63 publications

References 11 publications

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Pathways of Acetylcholine Synthesis, Transport and Release as Targets for Treatment of Adult-Onset Cognitive Dysfunction

Effect of Age on K+‐Induced Cytosolic Ca2+ Changes in Rat Cortical Synaptosomes

Biochemical pathology and treatment strategies in Alzheimer's disease: Emphasis on the cholinergic system

Contact Info

Product

Resources

About

Effect of Age on K⁺‐Induced Cytosolic Ca²⁺ Changes in Rat Cortical Synaptosomes