persistent deficits in hippocampal synaptic plasticity accompany losses of hippocampus-dependent memory in a rodent model of psychosis

déficits persistentes en la plasticidad sináptica hipocampal acompañan a pérdidas de memoria dependiente del hipocampo en un modelo de psicosis en roedores

Clicks: 371
ID: 159183
2013
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Steady

Ranked #22 of 89 articles by views in drug research

Most read Least read

Bar heights use a square-root scale.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Irreversible N-methyl-D-aspartate receptor (NMDAR) antagonism is known to provoke symptoms of psychosis and schizophrenia in healthy humans. NMDAR hypofunction is believed to play a central role in the pathophysiology of both disorders and in an animal model of psychosis, that is based on irreversible antagonism of NMDARs, pronounced deficits in hippocampal synaptic plasticity have been reported shortly after antagonist treatment. Here, we examined the long-term consequences for long-term potentiation (LTP) of a single acute treatment with an irreversible antagonist and investigated whether deficits are associated with memory impairments.The ability to express long-term potentiation (LTP) at the perforant pathway – dentate gyrus synapse, as well as object recognition memory was assessed 1, 2, 3 and 4 weeks after a single -treatment of the antagonist, MK801. Here, LTP in freely behaving rats was significantly impaired at all time-points compared to control LTP before treatment. Object recognition memory was also significantly poorer in MK801-treated compared to vehicle-treated animals for several weeks after treatment. Histological analysis revealed no changes in brain tissue.Taken together, these data support that acute treatment with an irreversible NMDAR antagonist persistently impairs hippocampal functioning on behavioral, as well as synaptic levels. The long-term deficits in synaptic plasticity may underlie the cognitive impairments that are associated with schizophrenia-spectrum disorders.
Se sabe que el antagonismo irreversible del receptor de N-metil-D-aspartato (NMDAR) provoca síntomas de psicosis y esquizofrenia en seres humanos sanos. Se cree que la hipofunción del NMDAR desempeña un papel central en la fisiopatología de ambos trastornos y, en un modelo animal de psicosis basado en el antagonismo irreversible de los NMDAR, se han descrito déficits pronunciados en la plasticidad sináptica hipocámpica poco después del tratamiento con el antagonista. En el presente trabajo, examinamos las consecuencias a largo plazo sobre la potenciación a largo plazo (LTP) de un único tratamiento agudo con un antagonista irreversible e investigamos si los déficits se asocian con alteraciones de la memoria. Se evaluó la capacidad de expresar potenciación a largo plazo (LTP) en la sinapsis de la vía perforante-giro dentado, así como la memoria de reconocimiento de objetos, a las 1, 2, 3 y 4 semanas posteriores a una única administración del antagonista MK801. En este estudio, la LTP en ratas en libre movimiento se vio significativamente deteriorada en todos los puntos temporales en comparación con la LTP de control previa al tratamiento. La memoria de reconocimiento de objetos también fue significativamente inferior en los animales tratados con MK801 en comparación con los tratados con vehículo durante varias semanas después del tratamiento. El análisis histológico no reveló cambios en el tejido cerebral. En conjunto, estos datos respaldan que el tratamiento agudo con un antagonista irreversible del NMDAR altera de manera persistente el funcionamiento hipocámpico, tanto a nivel conductual como sináptico. Los déficits a largo plazo en la plasticidad sináptica podrían subyacer a los deterioros cognitivos asociados a los trastornos del espectro de la esquizofrenia.
Reference Key
ewiescholleck2013frontierspersistent Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Valentina eWiescholleck;Denise eManahan-Vaughan
Journal drug research
Year 2013
DOI
10.3389/fnint.2013.00012
URL
http://journal.frontiersin.org/Journal/10.3389/fnint.2013.00012/full
Keywords
schizophrenia in vivo neurosciences dentate gyrus diseases of the nervous system neuropsychiatryneurology biological psychiatry long-term potentiation

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.