Myelination deficit in a phencyclidine-induced neurodevelopmental model of schizophrenia

Zhang, Ruiguo; He, Jue; Zhu, Shenghua; Zhang, Handi; Wang, Hongxing; Adilijiang, Abulimiti; Kong, Lynda; Wang, Junhui; Kong, Jiming; Tan, Qihua; Li, Xinmin

doi:10.1016/j.brainres.2012.06.003

Cited by 28 publications

(27 citation statements)

References 35 publications

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“…Third, dys myelination is consistently noted in neurodevelopmental models that reproduce behavioural features reminiscent of negative symptoms of schizophrenia. This includes perinatal and subchronic administration of phencyclidine, [70][71][72][73][74] ), early social isolation, 80 and excitotoxic developmental lesion models (medial prefrontal 81 ). Cuprizone, a copper chelating agent that actively disrupts myelination, results in diminished social interaction in mice, [81][82][83][84][85][86] but only when dys myelination occurs before adult life.…”

Section: The Role Of Myelin In Morphometrymentioning

confidence: 99%

The neurobiology of transition to psychosis

Palaniyappan

Das

Dempster

2017

JPN

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Section: The Role Of Myelin In Morphometrymentioning

confidence: 99%

The neurobiology of transition to psychosis

Palaniyappan

Das

Dempster

2017

JPN

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“…The expression pattern of p75 and TROY seems to recover over time, normalizing around adolescence as there are no significant differences in either p75 or TROY expression in the 5 week old rats (p>0.05). Furthermore, there are no significant alterations in MAP2 levels to indicate any significant alterations in neuronal 13 survival during adolescence (SF3). The levels of p75 and TROY are raised above control levels in the hippocampus of PCP treated rats by the time they reach adulthood at 14 weeks.…”

Section: Alterations Of P75 Troy and Myt1 In A Pcp Induced Neurodevementioning

confidence: 99%

“…The administration of PCP to rodents both induces neurotoxicity and causes major damage to all parts of the brain 13,14 . PCP administration at PN7, 9 and 11 has been repeatedly shown to result in an increase in neuronal degeneration in the frontal and cingulate cortex of rats 15,16 .…”

Section: Introductionmentioning

confidence: 99%

“…Oligodendrocytes, like neurons are sensitive to PCP toxicity during development 14 , and considering their significant role in axonal connectivity and conduction, disruption to these processes during early neurodevelopment can have significant negative consequences, impacting on normal brain 4 development. Furthermore, oligodendrocytes play a major role in myelination processes, which have been shown to be altered after PCP treatment in rats 13,14 . We have previously shown in this rat model that myelin basic protein (MBP), a marker of mature oligodendrocytes is significantly reduced in early development by perinatal administration of PCP 17 .…”

Section: Introductionmentioning

confidence: 99%

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Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats

Andrews

Newell

Matosin

et al. 2015

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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(2015). Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 63 91-97.Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats AbstractPostnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10 mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n = 6/group) were sacrificed at PN12, 5 weeks, or 14 weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001 ≤ p ≤ 0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5 weeks (p > 0.05). At 14 weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014 ≤ p ≤ 0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that components of the Lingo-1 signaling pathways may be involved in the acute neurotoxicity induced by perinatal administration of PCP in rats early in development and suggest that this may have implications for the hippocampal deficits seen in schizophrenia. Male Sprague Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN)7, 9 and 11. Rats (n=6/group) were sacrificed at PN12, 5 weeks or 14 weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001≤p≤0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5 we...

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“…It is a partial agonist of dopamine D2 receptors, which might explain the psychotic symptoms caused by PCP. In humans, PCP can cause schizophrenialike symptoms, and it has become a useful tool for developing animal models of this disease [39][40][41][42][43] …”

Section: Drugs For Developing An Animal Model Of Schizophreniamentioning

confidence: 99%

Prefrontal dysfunction and a monkey model of schizophrenia

et al. 2015

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The prefrontal cortex is implicated in cognitive functioning and schizophrenia. Prefrontal dysfunction is closely associated with the symptoms of schizophrenia. In addition to the features typical of schizophrenia, patients also present with aspects of cognitive disorders. Based on these relationships, a monkey model mimicking the cognitive symptoms of schizophrenia has been made using treatment with the non-specific competitive N-methyl-D-aspartate receptor antagonist, phencyclidine. The symptoms are ameliorated by atypical antipsychotic drugs such as clozapine. The benefi cial effects of clozapine on behavioral impairment might be a specifi c indicator of schizophrenia-related cognitive impairment. Keywords: prefrontal cortex; schizophrenia; monkey model ·Review· IntroductionOne percent of the adult population, particularly young adults, are affected by schizophrenia. Schizophrenic patients typically present with hallucinations, delusions, withdrawal from social activities, loss of personal care skills, and flat or inappropriate emotional responses to situations [1] . Although many factors have been associated with schizophrenia, including genetic factors, early environmental influences, and neurobiological, psychological, and sociological processes [2][3][4] that are very important contributory factors, the mechanism underlying this disorder is unknown. Patient data are insufficient for understanding the pathology and etiology of schizophrenia.Further, direct experimentation on human subjects is ethically unacceptable. Thus, animal models have become an indispensable tool for pathological research. Unlike other neurological diseases such as stroke, epilepsy, and Parkinson's disease that can be easily replicated in animals, some of the symptoms of schizophrenia human patients, such as thinking disorders, delusions, and hallucinations, are difficult to replicate in animals.For many years, there has been no appropriate nonhuman primate model of schizophrenia. In addition to the typical features of schizophrenia, patients present with aspects of prefrontal cognitive disorders involving, e.g., working memory, selective attention, initiating movement, and planning. Based on these relationships, a monkey model of schizophrenia could be developed by mimicking its cognitive symptoms. In this review, we introduce schizophrenia and the prefrontal cortex (PFC) as well as their relationship and discuss the development of a monkey model of schizophrenia, including the methods and behavioral tests of the model. The Prefrontal Cortex and SchizophreniaThe volume of the human brain is twice that of the chimpanzee, and the PFC, which is the most rostral component of the primate cortex, has expanded most in humans [5,6] . In other species, the PFC functions in voluntary motor control, whereas in primates, it has developed [5][6][7] . The PFC has broad connections with many parts of the brain, particularly the sub-regions of the limbic system [10] . The human PFC, which is better developed than in other primates, is the primary ...

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Myelination deficit in a phencyclidine-induced neurodevelopmental model of schizophrenia

Cited by 28 publications

References 35 publications

The neurobiology of transition to psychosis

The neurobiology of transition to psychosis

Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats

Prefrontal dysfunction and a monkey model of schizophrenia

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