Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats

Silva-Gómez, Adriana B.; Rojas, Darío; Juárez, Ismael; Flores, Gonzalo

doi:10.1016/s0006-8993(03)03042-7

Cited by 307 publications

(233 citation statements)

References 59 publications

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“…169 This animal model of stress was recently found to induce a decrease in dendritic length of pyramidal neurons from the hippocampus of rats. 170 A delicate balance between growth and elimination of synaptic connections appears to take place throughout life in response to learning and experience. 63 Elimination of synaptic connections peaks during adolescence as part of normal development and is likely to refine brain performance.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

Bellon

2007

Mol Psychiatry

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“…This pruning, though, occurs at a specific rate allowing optimization of synaptic connectivity and continuing development of important new connections (Katz and Shatz 1996;Zhang and Poo 2001;Huang, Chou et al 2005;Sur and Rubenstein 2005). If isolation rearing occurs during this developmental period, the dendrite spiny processes in the medial prefrontal cortex are reduced even beyond that of control rats (Silva-Gomez, Rojas et al 2003) suggesting abnormal neuronal plasticity due to isolation rearing. Our findings of decreased IEG expression in the mPFC in isolation reared rats during this developmental period are consistent with this finding in that both IEG expression (Lanahan and Worley 1998;Guzowski 2002) and dendrite spiny process development (Yuste and Bonhoeffer 2001) are measures of neuronal plasticity.…”

Section: Developmental and Anatomical Considerationsmentioning

confidence: 99%

Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats

Levine¹,

Leeder²,

Parekkadan³

et al. 2008

Neuroscience

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In addition to its maladaptive effects on psychiatric function, psychosocial deprivation impairs recovery from physical illness. Previously, we found that psychosocial deprivation, modeled by isolation rearing, depressed immediate early gene (IEG) expression in the medial prefrontal cortex (mPFC) and increased locomotion in the open field test (Levine, Youngs et al. 2007). In the present study, we examined whether similar changes in behavior and gene expression are associated with the maladaptive effects of psychosocial deprivation on physical injury healing. After weaning, anesthetized rats were subjected to a 20% total body surface area third degree burn injury and were subsequently either group or isolation reared. After four weeks of either isolation or group rearing (a period that encompasses rodent childhood and early adolescence), rats were sacrificed, and their healing and gene expression in the mPFC were assessed. Locomotion in the open field test was examined at 3 weeks post burn injury. We found that: 1) gross wound healing was significantly impaired in isolation reared rats compared to group reared rats, 2) locomotion was increased and IEG expression was suppressed for isolation reared rats during burn injury healing, 3) the decreased activity in the open field and increased IEG expression was greater for burn injury healing group reared rats than for uninjured group reared rats, 4) the degree of hyperactivity and IEG suppression was relatively similar between isolation reared rats during burn injury compared to uninjured isolation reared rats, 5) behavioral hyperactivity to novelty (the open

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“…At a cellular level, EE triggers an increase in the generation and integration of adult-born neurons into the granule cell layer (GCL) of the hippocampus and increases dendritic branching complexity and synapse formation in excitatory neurons of the hippocampus (Kempermann et al 1997(Kempermann et al , 1998van Praag et al 2000;Faherty et al 2003). Further, reduced sensory stimulation leads to a decrease in progenitor proliferation and dendrite branch patterns, which likely results in the wellcharacterized increase in depression and reduced cognitive capacity (Silva-Gomez et al 2003;Bianchi et al 2006;Ibi et al 2008). Importantly, retrospective analysis of humans exposed to psychosocial or behavioral enrichment appears to support the findings of animal studies (Cotman and Berchtold 2002;Agrigoroaei and Lachman 2011;Erickson et al 2011).…”

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confidence: 99%

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

et al. 2012

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Environmental enrichment (EE) has marked beneficial effects on cognitive capacity. Given the possibility that this form of neuronal plasticity could function via the actuation of the same cellular signaling pathways that underlie learning/memory formation, we examined whether the MAPK cascade effector, mitogen/stress-activated kinase 1 (MSK1), could play a role in this process. MSK1 functions as a key signaling intermediate that couples changes in neuronal activity into inducible gene expression, neuronal plasticity, and learning/memory. Here, we show that MSK1 is expressed in excitatory cell layers of the hippocampus, progenitor cells of the subgranular zone (SGZ), and adult-born immature neurons. MSK1 2/2 mice exhibit reduced spinogenesis and decreased dendritic branching complexity in hippocampal neurons, compared with WT mice. Further, in MSK1 2/2 mice, progenitor cell proliferation within the SGZ was significantly reduced and, correspondingly, the number of immature neurons within the dentate gyrus was significantly reduced. Consistent with prior work, MSK1 2/2 mice displayed deficits in both spatial and recognition memory tasks. Strikingly, cognitive enhancement resulting from a 40-d period of EE was markedly reduced in MSK1 2/2 animals. MSK1 2/2 mice exhibited reduced levels of EE-induced spinogenesis and SGZ progenitor proliferation. Taken together, these data reveal that MSK1 serves as a critical regulator of hippocampal physiology and function and that MSK1 serves as a key conduit by which enriching stimuli augment cellular plasticity and cognition.

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Decreased dendritic spine density on prefrontal cortical and hippocampal pyramidal neurons in postweaning social isolation rats

Cited by 307 publications

References 59 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

Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats

MSK1 regulates environmental enrichment-induced hippocampal plasticity and cognitive enhancement

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