Structural Abnormalities of Subicular Dendrites in Subjects With Schizophrenia and Mood Disorders

Rosoklija, Gorazd; Toomayan, Glen; Ellis, Steven P.; Keilp, John G.; Mann, Jim; Latov, Norman; Hays, Arthur P.; Dwork, Andrew J.

doi:10.1001/archpsyc.57.4.349

Cited by 339 publications

(214 citation statements)

References 46 publications

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“…They could open up new prospects for modeling the pathophysiology of schizophrenia. Not only have SUB anomalies reminiscent of neurodevelopmental failures been described in schizophrenia (Arnold et al, 1995;Arnold, 2000;Rosoklija et al, 2000;Law et al, 2004), but also a reduction in latent inhibition has been reported in neuroleptic-naive patients with schizophrenia (Baruch et al, 1988;Gray et al, 1992Gray et al, , 1995Lubow et al, 2000Rascle et al, 2001. Moreover, the dorsomedial shell part of the nucleus accumbens seems to be the target structure for the common action of neuroleptics (Deutch and Cameron, 1992;Robertson and Fibiger, 1992;Jennings et al, 2006), this being consistent with enhanced dopaminergic transmission in the dorsomedial shell in acute patients.…”

Section: Discussionmentioning

confidence: 88%

“…According to several recent proposals, the psychic disintegration characteristic of this disease would result from a defective connectivity between various integrative regions having a neurodevelopmental origin (Weinberger and Lipska, 1995;Bullmore et al, 1997;Friston, 1998;Lewis and Levitt, 2002;Sawa and Snyder, 2002;Arnold et al, 2005;Foucher et al, 2005). Thus, the ventral subiculum of the hippocampus (SUB) seems to be subjected to neurodevelopmental abnormalities in schizophrenia, as suggested by the cytoarchitectural and cortical morphometric aberrations reported by several authors, particularly in the left hemisphere (Arnold et al, 1995;Arnold, 2000;Rosoklija et al, 2000;Law et al, 2004). Data obtained over the past three decades also support the hypothesis of a functional dysregulation of the mesostriatal dopaminergic neurons in schizophrenia (Swerdlow and Koob, 1987;Harrison, 1999;Carlsson et al, 2001), consistent with a cortico-subcortical disconnectivity (Kegeles et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Meyer

Louilot

2011

Neuropsychopharmacol

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Schizophrenia would result from a defective connectivity between several integrative regions as a consequence of neurodevelopmental failure. Various anomalies reminiscent of early brain development disturbances have been observed in patients' left ventral subiculum of the hippocampus (SUB). Numerous data support the hypothesis of a functional dopaminergic dysregulation in schizophrenia. The common target structure for the action of antipsychotics appears to be a subregion of the ventral striatum, the dorsomedial shell part of the nucleus accumbens. Latent inhibition, a cognitive marker of interest for schizophrenia, has been found to be disrupted in acute patients. The present study set out to investigate the consequences of a neonatal functional inactivation of the left SUB by tetrodotoxin (TTX) in 8-day-old rats for the latent inhibition-related dopaminergic responses, as monitored by in vivo voltammetry in freely moving adult animals (11 weeks) in the left core and dorsomedial shell parts of the nucleus accumbens in an olfactory aversion procedure. Results obtained during the retention session of a threestage latent inhibition protocol showed that the postnatal unilateral functional blockade of the SUB was followed in pre-exposed TTXconditioned adult rats by a disruption of the behavioral expression of latent inhibition and induced a total and a partial reversal of the latent inhibition-related dopaminergic responses in the dorsomedial shell and core parts of the nucleus accumbens, respectively. The present data suggest that neonatal inactivation of the SUB has more marked consequences for the dopaminergic responses recorded in the dorsomedial shell part, than in the core part of the nucleus accumbens. These findings may provide new insight into the pathophysiology of schizophrenia.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Meyer

Louilot

2011

Neuropsychopharmacol

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“…Cytoarchitectural studies have found evidence for an increase in neuronal density, 9 decrease in neuronal size, 10,11 reduced pyramidal neuron dendritic field 12,13 and decreased dendritic spine density 14,15 with similar reductions in neuronal size observed in BPD. 16 Efforts to determine the neurochemical and molecular basis for these cellular alterations have revealed abnormalities in neurotransmission, signal transduction, inhibitory interneuron function and glial cells.…”

Section: Introductionmentioning

confidence: 92%

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

et al. 2007

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There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P < 0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.

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“…In the terminal fields of entorhinal cortex projections, SNAP-25 expression was decreased 85 . In the hippocampus it was shown that neuron populations had fewer dendritic spines and reduced dendritic arborizations 86 . This observation was supported by studies detecting molecular markers like microtubule-associated protein 2 (MAP2) and spinophilin 87,88 .…”

Section: Schizophrenia As a Disorder Of Disturbed Synaptic Plasticitymentioning

confidence: 99%

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

Schmitt

Reich‐Erkelenz²,

Gebicke‐Härter

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Schizophrenia is a severe neurobiological disease with genetic and environmental factors playing a role in the pathophysiology. Several brain regions have been implicated in the disease process and are connected in complex neuronal circuits. On the cellular and molecular level, affected connectivity between these regions, involving dysfunctional myelination of neuronal axons, as well as alterations on the synaptic level and energy metabolism of neurons leading to disturbances in synaptic plasticity are major findings in post-mortem studies. Microarray studies investigating genome-wide gene expression have contributed to the findings of alterations in complex pathways in relevant brain regions in schizophrenia. Moreover, first laser-capture microdissection studies allowed the investigation of gene expression in specific groups of neurons. However, it must be kept in mind that in post-mortem studies confounding effects of medication, mRNA quality as well as the capability of the brain for neuroplastic regenerative mechanisms in individuals with a lifetime history of schizophrenia may influence the complex pattern of alterations on the molecular level. Despite these limitations, hypothesis-free transcriptome studies in brain tissue from schizophrenia patients offer a unique possibility to learn more about underlying mechanisms, leading to new insights in the pathophysiology of the disease. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Keywords: Schizophrenia, gene expression, microarray, RT-PCR, in situ hybridization, brain regions. Schmitt ResumoEsquizofrenia é uma severa doença neurobiológica com fatores genéticos e ambientais desempenhando um papel na fisiopatologia. Diversas regiões cerebrais têm sido implicadas no processo da doença e estão conectadas em complexos circuitos neuronais. Nos níveis molecular e celular, a conectividade afetada entre essas regiões, envolvendo mielinização disfuncional dos axônios neuronais, bem como as alterações no nível sináptico e metabolismo energético levando a distúrbios na plasticidade sináptica, são os maiores achados em estudos post-mortem. Estudos de microarranjos investigando a expressão gênica contribuíram para os achados de alterações em vias complexas em regiões cerebrais relevantes na esquizofrenia. Além disso, estudos utilizando microdissecção e captura a laser permitiram a investigação da expressão gênica em grupos específicos de neurônios. Entretanto, deve ser mantido em mente que em estudos post-mortem, confusos efeitos de medicação, qualidade de RNAm, bem como capacidade de mecanismos regenerativos neuroplásticos do cérebro em indivíduos com história de vida de esquizofrenia, podem influenciar o complexo padrão de alterações no nível molecular. Apesar dessas limitações, estudos transcriptômicos livres de hipóteses em tecido cerebral de pacientes esquizofrênicos oferecem uma possibilidade única para aprender mais sobre os mecanismos subjacentes, levando a novas ópticas da fisiopatologia da doença. A, et al. / Rev Psiq Clín. 2013;40(1):10-5 Palavras-cha...

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Structural Abnormalities of Subicular Dendrites in Subjects With Schizophrenia and Mood Disorders

Cited by 339 publications

References 46 publications

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Latent Inhibition-Related Dopaminergic Responses in the Nucleus Accumbens are Disrupted Following Neonatal Transient Inactivation of the Ventral Subiculum

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

Estudos transcriptômicos no contexto da conectividade perturbada em esquizofrenia

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