Effects of MK-801 treatment across several pre-clinical analyses including a novel assessment of brain metabolic function utilizing PET and CT fused imaging in live rats

Daya, Ritesh P.; Bhandari, Jayant; Hui, Patricia; Tian, Yuxin; Farncombe, Troy; Mishra, Ram K.

doi:10.1016/j.neuropharm.2013.10.001

Cited by 12 publications

(9 citation statements)

References 58 publications

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“…Many of the pharmacological NMDAR hypofunction models utilize sub-chronic NMDAR antagonist administration of 5-7 days (Daya et al, 2014; Eyjolfsson et al, 2006; Hawken et al, 2013), or even shorter (Khella et al, 2014; Lopez-Gil et al, 2007; Manahan-Vaughan et al, 2008; Park et al, 2014) durations. In this study, we employed a 5-day NMDAR antagonist administration paradigm and found that it increased phosphorylation in the Akt/GS3K pathway, opposite to what we observed in SR−/− mice.…”

Section: Discussionmentioning

confidence: 99%

Subchronic pharmacological and chronic genetic NMDA receptor hypofunction differentially regulate the Akt signaling pathway and Arc expression in juvenile and adult mice

Takagi

Balu

Coyle

2015

Schizophrenia Research

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NMDA receptor (NMDAR) hypofunction is a compelling hypothesis for the pathophysiology of schizophrenia, because in part, NMDAR antagonists cause symptoms in healthy adult subjects that resemble schizophrenia. Therefore, NMDAR antagonists have been used as a method to induce NMDAR hypofunction in animals as a pharmacological model of schizophrenia. Serine racemase-null mutant (SR−/−) mice display constitutive NMDAR hypofunction due to the lack of D-serine. SR−/− mice have deficits in tropomysin-related kinase receptor (TrkB)/Akt signaling and activity regulated cytoskeletal protein (Arc) expression, which mirror what is observed in schizophrenia. Thus, we analyzed these signaling pathways in MK801 sub-chronically (0.15 mg/kg; 5 days) treated adult wild-type mice. We found that in contrast to SR−/− mice, the activated states of downstream signaling molecules, but not TrkB, were increased in MK801 treated mice. Furthermore, there is an age-dependent change in the behavioral reaction of people to NMDAR antagonists. We therefore administered the same dosing regimen of MK801 to juvenile mice and compared them to juvenile SR−/− mice. Our findings demonstrate that pharmacological NMDAR antagonism has different effects on TrkB/Akt signaling than genetically-induced NMDAR hypofunction. Given the phenotypic disparity between the MK801 model and schizophrenia, our results suggest that SR−/− mice more accurately reflect NMDAR hypofunction in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Subchronic pharmacological and chronic genetic NMDA receptor hypofunction differentially regulate the Akt signaling pathway and Arc expression in juvenile and adult mice

Takagi

Balu

Coyle

2015

Schizophrenia Research

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“…In contrast, data fusion is the use of different modalities to infer complementary and more comprehensive results than obtained by a single modality. The fusion of structural and functional modalities has been the subject of many studies such as fusion of MRI/PET (Cho et al, 2011;Prato et al, 2011;Chen et al, 2014), MRI/SPECT (Li and Wang, 2012), and CT/PET (Daya et al, 2014). In most cases, the combined modalities provide more promising results compared with a single modality.…”

Section: Image Registration and Data Fusionmentioning

confidence: 99%

Imaging and machine learning techniques for diagnosis of Alzheimer’s disease

Mirzaei

Adeli

2016

Reviews in the Neurosciences

114

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AbstractAlzheimer’s disease (AD) is a common health problem in elderly people. There has been considerable research toward the diagnosis and early detection of this disease in the past decade. The sensitivity of biomarkers and the accuracy of the detection techniques have been defined to be the key to an accurate diagnosis. This paper presents a state-of-the-art review of the research performed on the diagnosis of AD based on imaging and machine learning techniques. Different segmentation and machine learning techniques used for the diagnosis of AD are reviewed including thresholding, supervised and unsupervised learning, probabilistic techniques, Atlas-based approaches, and fusion of different image modalities. More recent and powerful classification techniques such as the enhanced probabilistic neural network of Ahmadlou and Adeli should be investigated with the goal of improving the diagnosis accuracy. A combination of different image modalities can help improve the diagnosis accuracy rate. Research is needed on the combination of modalities to discover multi-modal biomarkers.

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“…Impairment of working memory has previously been reported in NMDAR antagonist models, but the extension of the resultant deficits appears to be greatly dependent on the nature of the pharmacological approach [41,42,43]. The NOR test has consistently been used as a first screening for working memory [17] and significant deficits were reported for ketamine, MK-801 or PCP [43].…”

Section: Discussionmentioning

confidence: 99%

Repeated Exposure to Ketamine in Adolescent Rats Results in Persistent Anxiety in the Adulthood

Amorim¹,

Bravo²,

Silva³

et al. 2018

jdar

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Background. Adolescent development of the prefrontal cortex (PFC) is accompanied by important changes in glutamatergic, GABAergic and dopaminergic circuitries, susceptible to modulation by N-methyl-D-aspartate receptors (NMDAR) antagonists. Repeated ketamine was associated with social and memory deficits, but other relevant factors, such as anxiety, were not sufficiently addressed. The present study aimed to examine the behavioral and molecular consequences of repeated exposure to ketamine with a particular focus in anxiety. Methods. We treated male adolescent Wistar rats, starting postnatal day (PND) 35, with ketamine (30 mg/kg, i.p, 7 days). Behavioral evaluation was conducted in the adulthood (PND 60). The elevated plus maze (EPM) and open field tests were used to evaluate anxiety and locomotion, while sociability and novelty recognition were assessed through the novel object recognition (NOR) and the sociability and social novelty tests. At the end of the behavioral evaluation, brains were dissected and the prefrontal cortex used for biochemical evaluation. Results. Analysis of the elevated plus maze (EPM) data revealed a ketamine-induced anxiety-like profile, corroborated by the open field data. Ketaminetreated rats also failed to increase contact time with a conspecific in the social affiliation test and with an unknown rat in the novelty preference test. At the molecular level, frontal expression levels of tyrosine hydroxylase were found decreased. Conclusion. Altogether, these results show that repeated ketamine-exposure in the adolescent may result in long-term anxiety.

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Effects of MK-801 treatment across several pre-clinical analyses including a novel assessment of brain metabolic function utilizing PET and CT fused imaging in live rats

Cited by 12 publications

References 58 publications

Subchronic pharmacological and chronic genetic NMDA receptor hypofunction differentially regulate the Akt signaling pathway and Arc expression in juvenile and adult mice

Subchronic pharmacological and chronic genetic NMDA receptor hypofunction differentially regulate the Akt signaling pathway and Arc expression in juvenile and adult mice

Imaging and machine learning techniques for diagnosis of Alzheimer’s disease

Repeated Exposure to Ketamine in Adolescent Rats Results in Persistent Anxiety in the Adulthood

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