Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration

Fredriksson, Anders; Archer, Trevor; Alm, Henrik; Gordh, Torsten; Eriksson, Per

doi:10.1016/j.bbr.2003.12.026

Cited by 228 publications

(156 citation statements)

References 51 publications

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“…The treatment of neonatal mice with the benzodiazepine diazepam had no clear adverse effect on the acquisition of a spatial RAM task performed when the animals were adults (3 months of age). 43 Our results also showed that midazolam had no effect on the acquisition of the same task. Clear deficits were found in neonate mice treated with a combination of ketamine and a GABA agonist and later tested using the radial maze task (in adulthood).…”

Section: Discussionsupporting

confidence: 60%

The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice

2013

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The ketamine/midazolam association of a dissociative with a sedative agent is used for the induction and maintenance of anaesthesia in laboratory animals. Anaesthesia may interfere with research results through side-effects on the nervous system, such as memory impairment. It is known that ketamine and midazolam affect cognition; however, their effects have not been clarified when used in a context of balanced anaesthesia. Thus, this study evaluated the effects of ketamine/ midazolam on the acquisition of motor and of a spatial memory task in adult mice. Twenty-eight C57BL/6 adult male mice were divided into three groups: untreated control, treated with ketamine/midazolam (75 mg/kg / 10 mg/kg) and treated with midazolam (10 mg/kg) groups. Respiratory rate, heart rate and systolic pressure were measured every 5 min in the animals treated with ketamine/midazolam, as this was the only group that exhibited loss of the righting reflex. One day after treatment, animals were tested in the open field, rotarod and radial arm maze. There were no differences between treatments regarding open-field activity, rotarod performance or number of working and reference memory errors in the radial arm maze task. In conclusion, the learning process of spatial and motor tasks was not disrupted by the anaesthetic combination of ketamine/ midazolam. These results suggest its safe use in adult mice in projects where acquisition of a spatial and motor task is necessary.

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Section: Discussionsupporting

confidence: 60%

The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice

2013

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“…Long-term behavioural effects such as enhanced locomotion (Facchinetti et al, 1993, Harris et al, 2003, impairments in cognitive function as examined by spatial working memory, cognitive set-shifting, and other learning tests (Sircar, 2003, Fredriksson et al, 2004 and deficits in prepulse inhibition (Harris et al, 2003) are observed in adult rats and mice following perinatal NMDAR antagonist treatment. These behavioural changes mimic certain aspects of human schizophrenia and support the involvement of the glutamatergic system in schizophrenia-like symptoms.…”

Section: Introductionmentioning

confidence: 99%

Reciprocal signalling between NR2 subunits of the NMDA receptor and neuregulin1 and their role in schizophrenia

Geddes

Huang

Newell

2011

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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. (2011) Reciprocal signalling between NR2 subunits of the NMDA receptor and neuregulin 1 and their role in schizophrenia, Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 35, no. 4, 1 June 2011 pp. 896-904. Reciprocal signalling between NR2 subunits of the NMDA receptor and neuregulin 1 and their role in schizophrenia AbstractSchizophrenia is a debilitating neurodevelopmental psychiatric disorder. Both the N-methyl-D-aspartate receptor (NMDAR) and neuregulin1 (NRG1) are key molecules involved in normal brain development that have been linked to schizophrenia pathology and aetiology. The NR2 proteins are critical structural and functional subunits of the NMDAR and are developmentally and spatially regulated. Altered NR2 gene and protein expression has been found in human post-mortem schizophrenia brain tissue together with changes in NRG1 and its receptor ErbB4. The NR2 subunits and ErbB4 share a common anchoring domain on the postsynaptic density and therefore a disruption to either of these molecules may influence the functioning of the other. It has been shown that NRG1 signalling can affect NMDAR levels and function, particularly phosphorylation of the NR2 subunits. However little is known about the possible effects of NMDAR dysfunction on NRG1 signalling, which is important with regards to schizophrenia aetiology as numerous risk factors for the disorder can alter NMDAR functioning during early brain development. This review focuses on the role of the NMDA receptor subunits and NRG1 signalling in schizophrenia and proposes a mechanism by which a disruption to the NMDAR, particularly via altering the balance of NR2 subunits during early development, could influence NRG1 signalling. Tables : 1 2 Abstract Schizophrenia is a debilitating neurodevelopmental psychiatric disorder. Both the Nmethyl-D-aspartate receptor (NMDAR) and neuregulin1 (NRG1) are key molecules involved in normal brain development that have been linked to schizophrenia pathology and aetiology. The NR2 proteins are critical structural and functional subunits of the NMDAR and are developmentally and spatially regulated. Altered NR2 gene and protein expression has been found in human post-mortem schizophrenia brain tissue together with changes in NRG1 and its receptor ErbB4. The NR2 subunits and ErbB4 share a common anchoring domain on the postsynaptic density and therefore a disruption to either of these molecules may influence the functioning of the other. It has been shown that NRG1 signalling can affect NMDAR levels and function, particularly phosphorylation of the NR2 subunits. However not much is known about the possible effects of NMDAR dysfunction on NRG1 signalling, which is important with regards to schizophrenia aetiology as numerous risk factors for the disorder can alter NMDAR functioning during early brain development. This review focuses on the role of the NMDA receptor subunits and NRG1 signalling in schizophrenia and proposes a mechanism by which a disruption to the NMDAR, particularly via the altering...

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“…While some authors have found no adverse effects, others have shown ataxy and hallucinations in the newborns whose mothers were submitted to a propofol prolonged infusion [35,36]. Isoflurane is known to produce neurotoxicity in the fetus while it's controversy if sevoflurane and desflurane can cause same damages [37]. Despite sevoflurane is one of the most used agentes it was recently suggested that it could lead to neurotoxicity in newborn mices [37,38].…”

Section: Premature Birthmentioning

confidence: 99%

“…Isoflurane is known to produce neurotoxicity in the fetus while it's controversy if sevoflurane and desflurane can cause same damages [37]. Despite sevoflurane is one of the most used agentes it was recently suggested that it could lead to neurotoxicity in newborn mices [37,38]. It's known that nitrous oxide has effects on the DNA synthesis and thus can lead to teratogenicity [39].…”

Section: Premature Birthmentioning

confidence: 99%

Anesthesia for Non-Obstetrical Surgery during Pregnancy

Mandim¹

2014

General Med

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The number of surgical procedures in gravid women unrelated to pregnancy itself has been increased over years. In such cases, one must keep in mind the responsibility for two patients, the optimization and maintenance of maternal homeostasis, avoiding alterations on uteroplacental perfusion that can bring harm to the fetus. This review focus on safety to performing these procedures during pregnancy, considering the advances in the prevention and treatment of obstetric and fetal morbidity related to anesthesia. Background and Objectives:Despite research advances, there is still much controversy in the anesthetic management of obstetric patients. Several studies have demonstrated the safety of anesthesia in this group of patients. In this review an analysis of anesthetics used in clinical practice is proposed as well as the technique to be chosen and its effects on the mother and fetus in non-obstetric surgery during pregnancy.

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Neurofunctional deficits and potentiated apoptosis by neonatal NMDA antagonist administration

Cited by 228 publications

References 51 publications

The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice

The anaesthetic combination of ketamine/midazolam does not alter the acquisition of spatial and motor tasks in adult mice

Reciprocal signalling between NR2 subunits of the NMDA receptor and neuregulin1 and their role in schizophrenia

Anesthesia for Non-Obstetrical Surgery during Pregnancy

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