The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue

Brisch, Ralf; Saniotis, Arthur; Wolf, Rainer; Bielau, Hendrik; Bernstein, Hans‐Gert; Steiner, Johann; Bogerts, Bernhard; Braun, Katharina; Jankowski, Zbigniew; Kumaratilake, Jaliya; Henneberg, Maciej; Gos, Tomasz

doi:10.3389/fpsyt.2014.00047

Cited by 290 publications

(275 citation statements)

References 223 publications

Supporting

Mentioning

246

Contrasting

Unclassified

Order By: Relevance

“…Schizophrenia is a heterogeneous disorder characterized by a range of clinical features, such as positive symptoms, referring to psychotic behaviors, including hallucinations, and negative symptoms, associated with disruption of normal behavior, such as lack of motivation. The prevalence of schizophrenia has been reported to be 1% of the adult population, with development in late adolescence or early adulthood, and most patients suffer from the disease throughout their lifetime (163). Cognitive deficits affect sensory processing, episodic memory, processing speed, attention inhibition, working memory, and language and executive functions (164).…”

Section: Schizophreniamentioning

confidence: 99%

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

et al. 2015

View full text Add to dashboard Cite

SUMMARY Toxocara canis and T. cati are highly prevalent nematode infections of the intestines of dogs and cats. In paratenic hosts, larvae do not mature in the intestine but instead migrate through the somatic tissues and organs of the body. The presence of these migrating larvae can contribute to pathology. Toxocara larvae can invade the brains of humans, and while case descriptions of cerebral toxocariasis are historically rare, improved diagnosis and greater awareness have contributed to increased detection. Despite this, cerebral or neurological toxocariasis (NT) remains a poorly understood phenomenon. Furthermore, our understanding of cognitive deficits due to toxocariasis in human populations remains particularly deficient. Recent data describe an enhanced expression of biomarkers associated with brain injury, such as GFAP, AβPP, transforming growth factor β1 (TGF-β1), NF-L, S100B, tTG, and p-tau, in mice receiving even low doses of Toxocara ova. Finally, this review outlines a hypothesis to explore the relationship between the presence of T. canis larvae in the brain and the progression of Alzheimer's disease (AD) due to enhanced AD-associated neurodegenerative biomarker expression.

show abstract

Section: Schizophreniamentioning

confidence: 99%

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Within this framework, the PPI of the startle reflex is one of the most frequently used crossspecies paradigm to evaluate the sensorimotor gating response, known to be disrupted in schizophrenia, and proposed as a candidate neurophysiological endophenotype of this psychiatric disorder (Gottesmann, 2003). In line with the evidence that psychotomimetic drugs, such as Amph and PCP, trigger PPI deficits in both animals and humans, administration of these drugs represents the most widely validated experimental strategy to model schizophrenia-like symptoms in rodents (Braff et al, 2001;Brisch et al, 2014;Gargiulo and Landa De Gargiulo, 2014;Jones et al, 2011). Based on this consideration, in the attempt to move Rasd2 functional characterization from human to mouse, we evaluated whether lack of this GTPase in mutants influences sensorimotor gating responses in drug-free condition and after Amph or PCP treatment.…”

Section: Rasd2 Regulates Psychotomimetic Drug Effects D Vitucci Et Almentioning

confidence: 99%

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors’ in Mice

Vitucci

Giorgio

Napolitano

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Rasd2 is a thyroid hormone target gene, which encodes for a GTP-binding protein enriched in the striatum where, among other functions, it modulates dopaminergic neurotransmission. Here we report that human RASD2 mRNA is abundant in putamen, but it also occurs in the cerebral cortex, with a distinctive expression pattern that differs from that present in rodents. Consistent with its localization, we found that a genetic variation in RASD2 (rs6518956) affects postmortem prefrontal mRNA expression in healthy humans and is associated with phenotypes of relevance to schizophrenia, including prefrontal and striatal grey matter volume and physiology during working memory, as measured with magnetic resonance imaging. Interestingly, quantitative real-time PCR analysis indicated that RASD2 mRNA is slightly reduced in postmortem prefrontal cortex of patients with schizophrenia. In the attempt to uncover the neurobiological substrates associated with Rasd2 activity, we used knockout mice to analyze the in vivo influence of this G-protein on the prepulse inhibition of the startle response and psychotomimetic drug-related behavioral response. Data showed that Rasd2 mutants display deficits in basal prepulse inhibition that, in turn, exacerbate gating disruption under psychotomimetic drug challenge. Furthermore, we documented that lack of Rasd2 strikingly enhances the behavioral sensitivity to motor stimulation elicited by amphetamine and phencyclidine. Based on animal model data, along with the finding that RASD2 influences prefronto-striatal phenotypes in healthy humans, we suggest that genetic mutation or reduced levels of this G-protein might have a role in cerebral circuitry dysfunction underpinning exaggerated psychotomimetic drugs responses and development of specific biological phenotypes linked to schizophrenia.

show abstract

“…While the dopamine and glutamate hypotheses of schizophrenia are often presented as two independent central dogmas to understanding schizophrenia (Abi-Dargham 2004;Angrist et al 1974;Brisch et al 2014;Carlsson 1988;Gilmour et al 2012;Krystal et al 2003;Lau et al 2013;Tamminga 1998), the reality is schizophrenia is a heterogeneous disorder and therefore, it is very likely that elements of both hypotheses are correct. Accordingly, the sensitivity of rPAL to glutamatergic and dopaminergic challenges may be useful in the search for novel pharmacological treatments for schizophrenia, especially if the profiles of these impairments differ as this may allow the modeling of different underlying pathologies and symptom clusters (positive versus cognitive), within the same testing environment.…”

Section: Introductionmentioning

confidence: 97%

MK-801 and amphetamine result in dissociable profiles of cognitive impairment in a rodent paired associates learning task with relevance for schizophrenia

et al. 2015

View full text Add to dashboard Cite

Rationale Paired associates learning (PAL) has been suggested to be predictive of functional outcomes in first episode psychosis and of conversion from mild cognitive impairment to Alzheimer's disease. An automated touch screen-based rodent PAL (rPAL) task has been developed and is sensitive to manipulations of the dopaminergic and glutamatergic system. Accordingly, rPAL when used with pharmacological models of schizophrenia, like NMDA receptor blockade with MK-801 or dopaminergic stimulation with amphetamine, may have utility as a translational model of cognitive impairment in schizophrenia.Objective The purpose of this study was to determine if amphetamine-and MK-801-induced impairment represent distinct models of cognitive impairment by testing their sensitivity to common antipsychotics and determine the relative contributions of D1 versus D2 receptors on performance of PAL. Method Rats were trained in rPAL and were then treated with MK-801, amphetamine, risperidone, haloperidol, quinpirole, SK-82958, or SCH-23390 alone and in combination. Results While both amphetamine and MK-801 caused clear impairments in accuracy, MK-801 induced a profound Bperseverative^type behavior that was more pronounced when compared to amphetamine. Moreover, amphetamineinduced impairments, but not the effects of MK-801, could be reversed by antipsychotics as well as the D1 receptor antagonist SCH-23390, suggesting a role for both the D1 and D2 receptor in the amphetamine impairment model. Conclusions These data suggest that amphetamine and MK-801 represent dissociable models of impairment in PAL, dependent on different underlying neurobiology. The ability to distinguish dopaminergic versus glutamatergic effects on performance in rPAL makes it a unique and useful tool in the modeling of cognitive impairments in schizophrenia.

show abstract

The Role of Dopamine in Schizophrenia from a Neurobiological and Evolutionary Perspective: Old Fashioned, but Still in Vogue

Cited by 290 publications

References 223 publications

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

Rasd2 Modulates Prefronto-Striatal Phenotypes in Humans and ‘Schizophrenia-Like Behaviors’ in Mice

MK-801 and amphetamine result in dissociable profiles of cognitive impairment in a rodent paired associates learning task with relevance for schizophrenia

Contact Info

Product

Resources

About