Early dysfunction of central 5-HT system in a murine model of bovine spongiform encephalopathy

Vidal, Catherine; Herzog, Christian; Haeberlé, Anne-Marie; Bombarde, C.; Miquel, Marie‐Christine; Carimalo, Julie; Launay, Jean‐Marie; Mouillet-Richard, Sophie; Lasmézas, Corinne Ida; Dormont, Dominique; Kellermann, Odile; Bailly, Yannick

doi:10.1016/j.neuroscience.2009.02.072

Cited by 17 publications

(21 citation statements)

References 72 publications

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“…These observations fit in with the well-established notion that the 5-HT 1B R negatively controls anxiety46. They are also reminiscent of several reports that PrP 0/0 mice exhibit reduced anxiety in various paradigms4748. Interestingly, we previously documented that BSE-infected mice exhibited an anxiolytic-like behaviour similar to that of PrP 0/0 mice48.…”

Section: Discussionsupporting

confidence: 88%

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

Hernandez-Rapp

Martin-Lannerée

Hirsch

et al. 2014

Sci Rep

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The cellular prion protein, PrPC, is a glycosylphosphatidylinositol-anchored protein, abundant in lipid rafts and highly expressed in the brain. While PrPC is much studied for its involvement under its abnormal PrPSc isoform in Transmissible Spongiform Encephalopathies, its physiological role remains unclear. Here, we report that GSK3β, a multifunctional kinase whose inhibition is neuroprotective, is a downstream target of PrPC signalling in serotonergic neuronal cells. We show that the PrPC-dependent inactivation of GSK3β is relayed by a caveolin-Lyn platform located on neuronal cell bodies. Furthermore, the coupling of PrPC to GSK3β potentiates serotonergic signalling by altering the distribution and activity of the serotonin 1B receptor (5-HT1BR), a receptor that limits neurotransmitter release. In vivo, our data reveal an increased GSK3β kinase activity in PrP-deficient mouse brain, as well as sustained 5-HT1BR activity, whose inhibition promotes an anxiogenic behavioural response. Collectively, our data unveil a new facet of PrPC signalling that strengthens neurotransmission.

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Section: Discussionsupporting

confidence: 88%

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

Hernandez-Rapp

Martin-Lannerée

Hirsch

et al. 2014

Sci Rep

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“…Brains were removed and immersed for 24 h in Carnoy's fixative before being dehydrated and embedded in paraffin. Transverse sections (7 µm thick) were cut, and immunoperoxidase staining protocols were used for the detection of PrP Sc and TNFR1 using SAF32 (1 µg ml −1 ) and anti-TNFR1 (2 µg ml −1 ) antibodies, respectively 49,57,58 . The specificity of PrP Sc immunodetection was achieved by denaturing the PrP C by incubation of the sections in proteinase K (10 µg ml −1 ) for 10 min at 37 °C and subsequently in 3.4 M guanidine thiocyanate for 15 min.…”

Section: Competing Financial Interestsmentioning

confidence: 99%

PDK1 decreases TACE-mediated α-secretase activity and promotes disease progression in prion and Alzheimer's diseases

Pietri¹,

Dakowski²,

Hannaoui³

et al. 2013

Nat Med

112

148

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α-secretase-mediated cleavage of amyloid precursor protein (APP) precludes formation of neurotoxic amyloid-β (Aβ) peptides, and α-cleavage of cellular prion protein (PrP(C)) prevents its conversion into misfolded, pathogenic prions (PrP(Sc)). The mechanisms leading to decreased α-secretase activity in Alzheimer's and prion disease remain unclear. Here, we find that tumor necrosis factor-α-converting enzyme (TACE)-mediated α-secretase activity is impaired at the surface of neurons infected with PrP(Sc) or isolated from APP-transgenic mice with amyloid pathology. 3-phosphoinositide-dependent kinase-1 (PDK1) activity is increased in neurons infected with prions or affected by Aβ deposition and in the brains of individuals with Alzheimer's disease. PDK1 induces phosphorylation and caveolin-1-mediated internalization of TACE. This dysregulation of TACE increases PrP(Sc) and Aβ accumulation and reduces shedding of TNF-α receptor type 1 (TNFR1). Inhibition of PDK1 promotes localization of TACE to the plasma membrane, restores TACE-dependent α-secretase activity and cleavage of APP, PrP(C) and TNFR1, and attenuates PrP(Sc)- and Aβ-induced neurotoxicity. In mice, inhibition or siRNA-mediated silencing of PDK1 extends survival and reduces motor impairment following PrP(Sc) infection and in APP-transgenic mice reduces Alzheimer's disease-like pathology and memory impairment.

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“…Sc -infected brains, of the levels of serotonin, dopamine, and norepinephrine (25)(26)(27), as well as in the activity of monoaminergic receptors (28) and related enzymes, such as monoaminooxidase B (29) and adenylyl cyclase (30). Moreover, serotonergic dysfunction was observed in human clinical cases of fatal familial insomnia (31), and dopaminergic depletion was reported in patients with CreutzfeldtJakob disease, associated with rapid cognitive decline and movement disorders (32,33).…”

Section: Changes Were Reported In Prpmentioning

confidence: 99%

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

Beckman

Santos

Americo

et al. 2015

Journal of Biological Chemistry

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Background:The prion protein (PrP C ) functions as a scaffold for cell surface signaling systems, and plays a role in neurodegenerative diseases that include clinical depression among their symptoms. Results: PrP C -null mice showed depressive-like behavior concomitant with functional changes in monoaminergic systems. Conclusion: PrP C regulates functions of monoaminergic synapses. Significance: PrP C may be involved in major depression and related neuropsychiatric disorders.

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Early dysfunction of central 5-HT system in a murine model of bovine spongiform encephalopathy

Cited by 17 publications

References 72 publications

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

A PrPC-caveolin-Lyn complex negatively controls neuronal GSK3β and serotonin 1B receptor

PDK1 decreases TACE-mediated α-secretase activity and promotes disease progression in prion and Alzheimer's diseases

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

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