The endogenous peptide antisecretory factor promotes tonic GABAergic signaling in CA1 stratum radiatum interneurons

Strandberg, Joakim; Lindquist, Catarina; Lange, Stefan; Asztély, Fredrik; Hanse, Eric

doi:10.3389/fncel.2014.00013

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…205 Following release of i-tau into the extracellular space—a process that could result from neuronal death or stimulation 202 —e-tau can be internalized by other neurons via endocytosis, leading to prion-like spreading of tau pathology. 206 In addition, soluble e-tau might bind to muscarinic type 1 and type 3 receptors, thereby increasing intracellular calcium levels, which might facilitate further release of i-tau. 202 Tau released into the extracellular space is highly stable: 207 its CSF half-life is 12–14 h, 208 compared with about 2 h for Aβ.…”

Section: Clearance Of Taumentioning

confidence: 99%

Clearance systems in the brain—implications for Alzheimer disease

et al. 2015

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Accumulation of toxic protein aggregates—amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles—is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood–brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

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Section: Clearance Of Taumentioning

confidence: 99%

Clearance systems in the brain—implications for Alzheimer disease

et al. 2015

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“…Difficulties in diagnosing as well as in treating gliomas also depend on the particular location of these tumours, which are protected by the BBB. Many efforts have been, indeed, recently devoted to find out strategies which might improve permeability of BBB to CNS-directed drugs (for review see [ 68 ]), although, paradoxically, BBB leakage and the concomitant vasogenic edema (see below) are the main clinical problems in patients suffering from glioblastoma (for review see [ 69 ]). For all these reasons, new approaches are urgently needed for an early diagnosis of brain cancer and improvement of therapy.…”

Section: Brain Cancer Cellsmentioning

confidence: 99%

Section: Brain Cancer Cellsmentioning

confidence: 99%

“…Importantly, migration of glioma cells throughout the brain is also guided by the brain vessels, and cancer growth is associated with angiogenesis [ 69 ]. Proliferation of BCECs, to produce the new vessels, causes disruption of the tight junctions and generalized fragility of the BBB, which becomes leaky, thus creating the conditions for the vasogenic brain edema, the most serious clinical complication of glioblastoma [ 69 ]. Edema and glioma progression have been also correlated with altered expression of different isoforms of aquaporins (AQPs), a family of water channels of the plasma membrane [ 84 ], which are upregulated in brain cancer [ 85 – 89 ].…”

Section: Brain Cancer Cellsmentioning

confidence: 99%

“…An additional serious problem, posed by brain tumours, is the cancer-induced neuronal cell death and neurodegeneration. These events are associated with cytotoxic edema [ 69 , 96 ]. Again, extracellular vesicles are probably involved.…”

Section: Brain Cancer Cellsmentioning

confidence: 99%

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Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

Schiera

Liegro

2015

BioMed Research International

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Extracellular vesicles are involved in a great variety of physiological events occurring in the nervous system, such as cross talk among neurons and glial cells in synapse development and function, integrated neuronal plasticity, neuronal-glial metabolic exchanges, and synthesis and dynamic renewal of myelin. Many of these EV-mediated processes depend on the exchange of proteins, mRNAs, and noncoding RNAs, including miRNAs, which occurs among glial and neuronal cells. In addition, production and exchange of EVs can be modified under pathological conditions, such as brain cancer and neurodegeneration. Like other cancer cells, brain tumours can use EVs to secrete factors, which allow escaping from immune surveillance, and to transfer molecules into the surrounding cells, thus transforming their phenotype. Moreover, EVs can function as a way to discard material dangerous to cancer cells, such as differentiation-inducing proteins, and even drugs. Intriguingly, EVs seem to be also involved in spreading through the brain of aggregated proteins, such as prions and aggregated tau protein. Finally, EVs can carry useful biomarkers for the early diagnosis of diseases. Herein we summarize possible roles of EVs in brain physiological functions and discuss their involvement in the horizontal spreading, from cell to cell, of both cancer and neurodegenerative pathologies.

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Antisecretory Factor Modulates GABAA Receptor Activity in Neurons

et al. 2018

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The antisecretory factor is an endogenous protein found in all mammalian tissues investigated so far. It acts by counteracting intestinal hypersecretion and various forms of inflammation, but the detailed mechanism of antisecretory factor (AF) action is unknown. We tested neuronal GABA receptors by means of AF-16, a potent AF peptide derived from amino acids 36-51 from the NH part of AF. Cultured rat cerebellar granule cells were used, and the effects on the GABA-mediated chloride currents were determined by whole-cell patch clamp. Both the neurotransmitter GABA and AF-16 were added by perfusion of the experimental system. A 3-min AF-16 preincubation was more efficacious than 30 s in significantly elevating the rapidly desensitizing GABA-activated chloride current. No effect was found on the tonic, slowly desensitizing current. The GABA-activated current increase by AF-16 demonstrated a low k of 41 pM with a maximal increase of 37% persisting for some minutes after AF washout, independent from GABA concentration. This indicates an effect on the maximal stimulation (E%) excluding an altered affinity between GABA and its receptor. An immunocytochemical fluorescence approach with anti γ2 subunit antibodies demonstrated an increased expression of GABA receptors. Thus, both the electrophysiological and the immunofluorescence approach indicate an increased appearance of GABA receptors on the neuronal membrane. The rationale of the experiments was to test the effect of AF on a defined neuronal population of GABA receptors. The implications of the results on the impact of AF on the enteric nervous system or on brain function are discussed.

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The endogenous peptide antisecretory factor promotes tonic GABAergic signaling in CA1 stratum radiatum interneurons

Cited by 7 publications

References 45 publications

Clearance systems in the brain—implications for Alzheimer disease

Clearance systems in the brain—implications for Alzheimer disease

Extracellular Membrane Vesicles as Vehicles for Brain Cell-to-Cell Interactions in Physiological as well as Pathological Conditions

Antisecretory Factor Modulates GABAA Receptor Activity in Neurons

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