Antipsychotic treatment induces alterations in dendrite- and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex

@article{Lidow2001AntipsychoticTI,
  title={Antipsychotic treatment induces alterations in dendrite- and spine-associated proteins in dopamine-rich areas of the primate cerebral cortex},
  author={M. Lidow and Zan-Min Song and S. Castner and P. Allen and P. Greengard and P. Goldman-Rakic},
  journal={Biological Psychiatry},
  year={2001},
  volume={49},
  pages={1-12}
}
BACKGROUND Mounting evidence indicates that long-term treatment with antipsychotic medications can alter the morphology and connectivity of cellular processes in the cerebral cortex. The cytoskeleton plays an essential role in the maintenance of cellular morphology and is subject to regulation by intracellular pathways associated with neurotransmitter receptors targeted by antipsychotic drugs. METHODS We have examined whether chronic treatment with the antipsychotic drug haloperidol… Expand
Clozapine and haloperidol differentially regulate dendritic spine formation and synaptogenesis in rat hippocampal neurons
TLDR
It is demonstrated that in rat dissociated hippocampal neurons 1.0 microM clozapine administration increased DS-enriched protein spinophilin by 70%, increased post-synaptic protein shank1a puncta density by 26% and increased overall primary dendrite DS density by 59%. Expand
Spinophilin expression in postmortem prefrontal cortex of schizophrenic subjects: Effects of antipsychotic treatment
TLDR
The results suggest that antipsychotics could produce alterations in spinophilin expression that do not seem to be related to schizophrenia per se, and may underlie some of the side effects of antipsychotic drugs. Expand
Antipsychotics increase microtubule‐associated protein 2 mRNA but not spinophilin mRNA in rat hippocampus and cortex
TLDR
Overall, results show a modulation of MAP2 gene expression, likely reflecting functional or structural changes in the dendritic tree in response to some typical and atypical antipsychotics, which provides further evidence that antippsychotics regulate genes involved in synaptic structure and function. Expand
Reduced Cortical Volume and Elevated Astrocyte Density in Rats Chronically Treated With Antipsychotic Drugs—Linking Magnetic Resonance Imaging Findings to Cellular Pathology
TLDR
Ex vivo magnetic resonance imaging data demonstrates region-specific structural effects of chronic APD treatment on the rat cortex, primarily but not exclusively localized to the ACC, which is likely to reflect a loss of neuropil. Expand
Presynaptic proteins in the prefrontal cortex of patients with schizophrenia and rats with abnormal prefrontal development
TLDR
The data suggest that apparently profound prefrontal cortical dysfunction in schizophrenia, as well as in an animal model of schizophrenia, may exist without gross changes in the abundance of many synaptic proteins but discrete changes in selected presynaptic molecules may be present. Expand
Effects of antipsychotic drugs on the expression of synaptic proteins and dendritic outgrowth in hippocampal neuronal cultures
TLDR
The results suggest that the up‐regulation of synaptic proteins and dendritic outgrowth may represent key effects of some atypical antipsychotic drugs but that haloperidol may be associated with distinct actions. Expand
Microtubule-associated protein MAP2 expression in olfactory bulb in schizophrenia
TLDR
Examination of expression in the OB of the microtubule-associated protein MAP2 found that significantly reduced in schizophrenia, while phosphorylated MAP2 expression did not differ between groups, are consistent with faulty OB innervation in schizophrenia. Expand
Effects of antipsychotic drugs on the expression of synapse-associated proteins in the frontal cortex of rats subjected to immobilization stress
TLDR
Results indicate that olanzapine and aripiprazole, and, haloperidol, differentially regulate the levels of synapse-associated proteins in the rat frontal cortex. Expand
Abnormalities in the dopamine system in schizophrenia may lie in altered levels of dopamine receptor-interacting proteins
TLDR
Up-regulation of calcyon and NCS-1 in the second schizophrenia cohort strengthens the proposition that abnormalities of the dopamine system in this disease may lie in altered levels of dopamine receptor-interacting proteins. Expand
Proteome and pathway effects of chronic haloperidol treatment in mouse hippocampus
TLDR
The findings of this study could stimulate further research into the cellular mechanisms associated with haloperidol treatment and the pathophysiology of psychotic disorders, assisting treatment biomarker discovery. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 105 REFERENCES
Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure
TLDR
The findings indicate that glial proliferation and hypertrophy of the cerebral cortex is a common response to antipsychotic drugs and it is hypothesized that these responses play a regulatory role in adjusting neurotransmitter levels or metabolic processes. Expand
Levels of the growth-associated protein GAP-43 are selectively increased in association cortices in schizophrenia.
TLDR
It is proposed that schizophrenia is associated with a perturbed organization of synaptic connections in distinct cortical associative areas of the human brain, and that increased levels of GAP-43 are one manifestation of this dysfunctional organization. Expand
Chronic haloperidol treatment differentially affects the expression of synaptic and neuronal plasticity-associated genes
TLDR
The persistent increase in synaptophysin expression supports the evidence that chronic antipsychotic drug treatment induces synaptic reorganisation in some striatal and cortical neuron populations, whereas the GAP-43 mRNA data suggest that haloperidol does not produce a sustained alteration of neuronal plasticity. Expand
Synaptic rearrangements in medial prefrontal cortex of haloperidol-treated rats
TLDR
The data suggest the possibility that haloperidol may have induced a relocation of asymmetric terminals from resorbed spinous processes to larger dendritic branches with the concomitant loss of their postsynaptic membrane specialization. Expand
Reduction of synaptophysin immunoreactivity in the prefrontal cortex of subjects with schizophrenia. Regional and diagnostic specificity.
TLDR
Levels of synaptophysin immunoreactivity in prefrontal cortical areas 46, 9, and 17 did not differ between 5 nonschizophrenic psychiatric case subjects and their matched controls, suggesting that decreased synaptophysicalin levels in the prefrontal cortex of patients with schizophrenia may be specific to that disorder. Expand
Abnormal expression of two microtubule-associated proteins (MAP2 and MAP5) in specific subfields of the hippocampal formation in schizophrenia.
TLDR
Defects in the expression of MAP2 and MAP5, two proteins that contribute to the establishment and maintenance of neuronal polarity, could underlie some of the cytoarchitectural abnormalities described in schizophrenia and impair signal transduction in the affected dendrites. Expand
The effects of chronic haloperidol administration on GABA‐immunoreactive. Axon terminals in rat medial prefrontal cortex
TLDR
Data from a quantitative light microscopic analysis of GABA‐immunolabeled axosomatic terminals in mPFC of rats treated with HAL decanoate are consistent with the idea that chronic HAL administration may be associated with a significant increase in the amount of GABA present in terminals surrounding pyramidal neurons of rat mP FC. Expand
Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs.
TLDR
A reduction in the levels of prefrontal cortical dopamine receptors of the D1 class may be an obligatory consequence of D2 receptor antagonism and thus may be a pharmacological property of antipsychotic drugs. Expand
Synaptic and plasticity-associated proteins in anterior frontal cortex in severe mental illness
TLDR
The hypothesis that synaptic abnormalities are a substrate for disordered connectivity in severe mental illness is supported, and it is suggested that synaptic-oligodendroglial interactions may contribute to the mechanism of dysregulation in certain cases. Expand
Alterations in synaptic proteins and their encoding mRNAs in prefrontal cortex in schizophrenia: a possible neurochemical basis for ‘hypofrontality’
An impairment of prefrontal cortical functioning in schizophrenia (‘hypofrontality’) has been suggested by clinical, neuroimaging, and postmortem brain tissue studies. We used Western immunoblot andExpand
...
1
2
3
4
5
...