Cholinergic denervation attenuates phencyclidine-induced c-fos responses in rat cortical neurons

Savage, S.; Mattsson, Anna; Olson, Lar̀s

doi:10.1016/j.neuroscience.2012.04.064

Cited by 3 publications

(2 citation statements)

References 126 publications

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“…Cortical levels of the Lingo-1 co-receptors NgR and p75 were not significantly altered by PCP treatment at any of the three developmental time-points (Figure 2), this is in accordance with two previous studies showing that NgR mRNA expression is not altered following PCP treatment in rats (73), and that p75 protein expression is not altered by PCP treatment in cortical cultured neurons (74).…”

Section: Discussionsupporting

confidence: 92%

Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats

et al. 2018

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Postnatal administration of phencyclidine (PCP) in rodents causes major brain dysfunction leading to severe disturbances in behavior lasting into adulthood. This model is routinely employed to model psychiatric disorders such as schizophrenia, as it reflects schizophrenia related brain disturbances including increased apoptosis, and disruptions to myelin and plasticity processes. Leucine-rich repeat and immunoglobulin domain-containing protein, Lingo-1, is a potent negative regulator of both axonal myelination and neurite extension. The Nogo receptor (NgR)/TNF receptor orphan Y (TROY) and/or p75 complex, With No Lysine (K) (WNK1) and Myelin transcription factor-1 (Myt1) are co-receptors or co-factors in Lingo-1 signaling pathways in the brain. We have examined the developmental trajectory of these proteins in a neurodevelopmental model of schizophrenia using PCP to determine if Lingo-1 pathways are altered in the prefrontal cortex throughout different stages of life. Sprague Dawley rats were injected with PCP (10mg/kg) or saline on postnatal days (PN)7, 9 and 11 and sacrificed at PN12, 5 weeks or 14 weeks for measurement of Lingo-1 signaling proteins in the prefrontal cortex. Myt1 was decreased by PCP at PN12 (p=0.045), and at 14 weeks PCP increased Lingo-1 (p=0.037), TROY (p=0.017) and WNK1 (p=0.003) expression. This is the first study reporting an alteration in Lingo-1 signaling proteins in the rat prefrontal cortex both directly after PCP treatment in early development and in adulthood. We propose that Lingo-1 pathways may be negatively regulating myelination and neurite outgrowth following the administration of PCP, and that this may have implications for the cortical dysfunction observed in schizophrenia.

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Section: Discussionsupporting

confidence: 92%

Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats

et al. 2018

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“…Besides glutamate, other neurotransmitters including GABA ( 26 ), serotonin ( 27 ), acetylcholine ( 28 , 29 ) and dopamine ( 30 ) have all been reported to be involved in the regulation of PPI, but the intracellular signaling molecules are unknown. In contrast, NMDAR signaling has been extensively studied.…”

Section: Introductionmentioning

confidence: 99%

Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex

et al. 2015

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Prepulse inhibition (PPI) is an example of sensorimotor gating and deficits in PPI have been demonstrated in schizophrenia patients. Phencyclidine (PCP) suppression of PPI in animals has been studied to elucidate the pathological elements of schizophrenia. However, the molecular mechanisms underlying PCP treatment or PPI in the brain are still poorly understood. In this study, quantitative phosphoproteomic analysis was performed on the prefrontal cortex from rats that were subjected to PPI after being systemically injected with PCP or saline. PCP down-regulated phosphorylation events were significantly enriched in proteins associated with long-term potentiation (LTP). Importantly, this dataset identifies functionally novel phosphorylation sites on known LTP-associated signaling molecules. In addition, mutagenesis of a significantly altered phosphorylation site on xCT (SLC7A11), the light chain of system xc-, the cystine/glutamate antiporter, suggests that PCP also regulates the activity of this protein. Finally, new insights were also derived on PPI signaling independent of PCP treatment. This is the first quantitative phosphorylation proteomic analysis providing new molecular insights into sensorimotor gating.

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Phencyclidine (Angel Dust, PCP) and Fos Immunoreactivity

Yamamoto

Sawada

Kamegaya

et al. 2016

Neuropathology of Drug Addictions and Substance Misuse

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Cholinergic denervation attenuates phencyclidine-induced c-fos responses in rat cortical neurons

Cited by 3 publications

References 126 publications

Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats

Perinatal administration of phencyclidine alters expression of Lingo-1 signaling pathway proteins in the prefrontal cortex of juvenile and adult rats

Global quantitative analysis of phosphorylation underlying phencyclidine signaling and sensorimotor gating in the prefrontal cortex

Phencyclidine (Angel Dust, PCP) and Fos Immunoreactivity

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