The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients

Kalus, Peter; Müller, Thomas; Zuschratter, Werner; Senitz, D

doi:10.1097/00001756-200011090-00044

Cited by 131 publications

(82 citation statements)

References 13 publications

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“…34 In addition, loss of MAP2 was also reported in the medial prefrontal cortex (PFC) of patients with this same disorder. 35 A decrease in dendritic length was encountered by a 3D image analysis on the PFC of patients with schizophrenia 36 and similar results were evidenced in the hippocampus. 37 Reduced interneuronal space, decreased dendritic markers, smaller neuronal soma sizes and a reduction in dendritic length are all findings that support the 'reduced neuropil hypothesis'.…”

Section: Introductionsupporting

confidence: 66%

New genes associated with schizophrenia in neurite formation: a review of cell culture experiments

Bellon

2007

Mol Psychiatry

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New genes consistently associated with schizophrenia include NRG1, Akt, DISC-1 and dysbindin-1. Since these genes participate in neurotransmission, neuroplasticity and neurodevelopment it has not been easy to elucidate which of these roles are abnormal in patients with schizophrenia. Neurite formation is identified as a crucial stage in development, and it is proposed that a defect in neurite formation originating from abnormally encoded proteins by these new genes could be at least an in vitro marker that reflects the most consistent molecular and neuroanatomical findings in schizophrenia. A systematic review of the literature linking the process of neurite formation to genes with replicated evidence that supported their association with schizophrenia was conducted. In addition, an outline of the process of neurite formation was included. Neurite formation was shown to be induced by neuregulins, the product of the gene NRG1. The activation of Akt, a serine/threonine kinase, promoted neurite formation in six independent studies. Conversely, two studies found that Akt inhibits neurite outgrowth. Stronger evidence supporting an association with the new genes related to schizophrenia and neurite formation comes from DISC-1. Defects in DISC-1 protein were shown to directly alter the process of neurite formation. Dysbindin-1 has not yet been directly implicated in neurite outgrowth. These findings suggest that the proteins encoded by NRG1, Akt and DISC-1 are implicated in the process of neurite formation in cellular models as well as, at least in part, animal models during development. Abnormalities in this process could have potential etiologic implications for schizophrenia. Direct evidence, however, of abnormal neurite formation in patients with schizophrenia is still missing. Limitations to this model are identified.

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Section: Introductionsupporting

confidence: 66%

New genes associated with schizophrenia in neurite formation: a review of cell culture experiments

Bellon

2007

Mol Psychiatry

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“…Studies examining the dendritic morphology of Golgiimpregnated pyramidal neurons in the prefrontal cortex of schizophrenic patients and have found reductions in spine density, dendritic complexity, and dendritic length that are consistent with the postulated reduction in cortical communication (Garey et al, 1998;Glantz and Lewis, 2000;Kalus et al, 2000;Broadbelt et al, 2002;Black et al, 2004). In the AMPH-sensitized monkey, we observed a reduction in complexity of dendrites in layer II/IIIs and a reduction in dendritic length in pyramidal cells across all layers.…”

Section: Implications For the Neuropathology Of The Prefrontal Cortexsupporting

confidence: 83%

“…However, evidence linking disturbances in dopamine neurotransmission to structural pathology in the brain has been lacking. For example, post-mortem studies of the prefrontal cortex from patients with schizophrenia patients have described reductions in spine density, dendritic length, and complexity in the basilar dendrites of pyramidal cells in layers III and V (Garey et al, 1998;Glantz and Lewis, 2000;Kalus et al, 2000;Broadbelt et al, 2002;Black et al, 2004). However, it is not known whether there is a causal effect between the purported neurochemical imbalance in the dopaminergic innervation of the prefrontal cortex and the observed abnormalities in dendritic architecture of pyramidal cells in this region.…”

Section: Introductionmentioning

confidence: 99%

Amphetamine Sensitization Alters Dendritic Morphology in Prefrontal Cortical Pyramidal Neurons in the Non-Human Primate

Selemon

Begovic

Goldman‐Rakic

et al. 2006

Neuropsychopharmacol

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Amphetamine (AMPH) sensitization in the nonhuman primate induces persistent aberrant behaviors reminiscent of the hallmark symptoms of schizophrenia, including hallucinatory-like behaviors, psychomotor depression, and profound cognitive impairment. The present study examined whether AMPH sensitization induces similarly long-lasting morphologic alterations in prefrontal cortical pyramidal neurons. Three to 3 1 2 years postsensitization, sensitized, and AMPH-naïve control monkeys were killed. Blocks of prefrontal cortex were Golgi-impregnated for elucidation of pyramidal dendritic morphology in layers II/superficial III (II/IIIs), deep III, and V/VI. In AMPH-sensitized animals as compared to AMPH-naïve controls, pyramidal dendrites in layer II/IIIs exhibited reduced overall dendritic branching and reduced peak spine density (22%) on the apical trunk. Across all layers, the distance from soma to peak spine density along the apical trunk was decreased (126.3877.65 mm in AMPH-sensitized compared to 162.9877.26 mm in AMPH-naïve controls), and basilar dendritic length was reduced (32%). These findings indicate that chronic dopamine dysregulation, consequent to AMPH sensitization, results in enduring, atrophic changes in prefrontal pyramidal dendrites that resemble the pathologic alterations described in patients with schizophrenia and may contribute to the persistence of schizophrenia-like behavioral changes and cognitive dysfunction associated with sensitization. These findings may also provide key insights into the etiologic origin of the pronounced behavioral disturbances and cognitive dysfunction associated with schizophrenia. Neuropsychopharmacology (2007) 32, 919-931.

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“…In fact, a recent study has demonstrated a strong correlation between the loss of asymmetric spine synapses in monkey PFC and cognitive impairment during aging (Peters et al, 2008). Several groups have reported dystrophic changes in frontal cortical pyramidal cell dendrites in schizophrenia, including decreases in dendritic length, branching, and spine density (Black et al, 2004;Broadbelt et al, 2002;Garey et al, 1998;Glantz and Lewis, 2000;Kalus et al, 2000;Kolluri et al, 2005), consistent with the hypothesis that these changes are involved in the cognitive dysfunction that typifies the disorder. It is not currently known though whether the pathological changes in the cortex in schizophrenia are fixed or can be altered by treatment with antipsychotic drugs.…”

Section: Introductionmentioning

confidence: 69%

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

Elsworth

Morrow

Hajszán

et al. 2011

Neuropsychopharmacol

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Enduring cognitive deficits exist in schizophrenic patients, long-term abusers of phencyclidine (PCP), as well as in animal PCP models of schizophrenia. It has been suggested that cognitive performance and memory processes are coupled with remodeling of pyramidal dendritic spine synapses in prefrontal cortex (PFC), and that reduced spine density and number of spine synapses in the medial PFC of PCP-treated rats may potentially underlie, at least partially, the cognitive dysfunction previously observed in this animal model. The present data show that the decrease in number of asymmetric (excitatory) spine synapses in layer II/III of PFC, previously noted at 1-week post PCP treatment also occurs, to a lesser degree, in layer V. The decrease in the number of spine synapses in layer II/III was sustained and persisted for at least 4 weeks, paralleling the observed cognitive deficits. Both acute and chronic treatment with the atypical antipsychotic drug, olanzapine, starting at 1 week after PCP treatment at doses that restore cognitive function, reversed the asymmetric spine synapse loss in PFC of PCP-treated rats. Olanzapine had no significant effect on spine synapse number in saline-treated controls. These studies demonstrate that the effect of PCP on asymmetric spine synapse number in PFC lasts at least 4 weeks in this model. This spine synapse loss in PFC is reversed by acute treatment with olanzapine, and this reversal is maintained by chronic oral treatment, paralleling the time course of the restoration of the dopamine deficit, and normalization of cognitive function produced by olanzapine.

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The dendritic architecture of prefrontal pyramidal neurons in schizophrenic patients

Cited by 131 publications

References 13 publications

New genes associated with schizophrenia in neurite formation: a review of cell culture experiments

New genes associated with schizophrenia in neurite formation: a review of cell culture experiments

Amphetamine Sensitization Alters Dendritic Morphology in Prefrontal Cortical Pyramidal Neurons in the Non-Human Primate

Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine

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