Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline

Stevens, Karen E.; Adams, Catherine E.; Yonchek, Joan; Hickel, Cindy; Danielson, Jeffrey J.; Kisley, Michael A.

doi:10.1007/s00213-008-1170-3

Cited by 52 publications

(58 citation statements)

References 65 publications

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“…Conversely, choline deficiency during these sensitive periods results in altered memory function and associated cognitive deficits that also persist (Meck and Williams 1997c. Furthermore, recent studies suggest that perinatal choline supplementation can alleviate the cognitive effects of postnatal, human-third-semester pregnancy equivalent, alcohol exposure in rat offspring (e.g., Thomas et al 2000Thomas et al , 2004Thomas et al , 2007, and ameliorate brain growth factor and sensorimotor deficiencies in mouse models of schizophrenia and Rett syndrome (e.g., Nag and Berger-Sweeney 2007; Stevens et al 2008). The likely mechanism for these effects of choline involves an epigenetic change in DNA methylation, altered gene expression, and resulting changes in stem cell proliferation and differentiation (Zeisel 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Choline deficiency during the same developmental time frame, embryonic days (ED) 12-17, results in impaired performance on some, but not all, of these behavioral measures (e.g., Williams 1999, 2003). Furthermore, perinatal choline supplementation can alter behavior following a variety of developmental disorders, including the alleviation of abnormalities associated with fetal alcohol syndrome in rats (Thomas et al 2000(Thomas et al , 2004(Thomas et al , 2007Wagner and Hunt 2006), attenuation of some of the motor deficits observed in a Mecp21 lox mouse model of Rett syndrome (Nag and BergerSweeney 2007), and the improvement of sensory gating in a DBA/2 mouse model of schizophrenia that exhibits reduced numbers of hippocampal a7 nicotinic receptors (Stevens et al 2008).…”

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confidence: 99%

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Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

Lamoureux¹,

Meck²,

Williams³

2008

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The effects of prenatal choline availability on Pavlovian conditioning were assessed in adult male rats (3-4 mo). Neither supplementation nor deprivation of prenatal choline affected the acquisition and extinction of simple Pavlovian conditioned excitation, or the acquisition and retardation of conditioned inhibition. However, prenatal choline availability significantly altered the contextual control of these learned behaviors. Both control and choline-deprived rats exhibited context specificity of conditioned excitation as exhibited by a loss in responding when tested in an alternate context after conditioning; in contrast, choline-supplemented rats showed no such effect. When switched to a different context following extinction, however, both choline-supplemented and control rats showed substantial contextual control of responding, whereas choline-deficient rats did not. These data support the view that configural associations that rely on hippocampal function are selectively sensitive to prenatal manipulations of dietary choline during prenatal development.There is increasing evidence that variations in maternal dietary choline intake during the second half of pregnancy cause structural, biochemical, and physiological changes in basal forebrain neurons and their projections to the hippocampal complex as well as long-term cognitive changes in the offspring (e.g., Meck and Williams 2003;McCann et al. 2006;Meck et al. 2008). We know, for instance, that the adult offspring of pregnant rats supplemented with 4.5 times the amount of choline in the standard laboratory diet display improved memory capacity and precision on the radial-arm maze (e.g., Meck et al.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

Lamoureux¹,

Meck²,

Williams³

2008

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“…In addition, mice treated during gestation with choline develop increased numbers of alpha7 receptors in the hippocampus [124]. Thus, DBA/2 mice that have deficient sensory inhibition and reduced numbers of alpha7 nicotinic receptors in the hippocampus showed an increased number of alpha7 receptors and improved sensory inhibition following prenatal choline supplementation [125].…”

Section: Pharmacological Approachesmentioning

confidence: 98%

Alpha7 Neuronal Nicotinic Receptors as Targets for Novel Therapies to Treat Multiple Domains of Schizophrenia

Kucinski¹,

Stachowiak²,

Wersinger³

et al. 2011

CPB

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A number of hypotheses have been put forth to explain the underlying abnormalities of schizophrenia. The widely held dopamine hypothesis suggests that positive symptoms are related to elevated subcortical dopamine transmission and that negative symptoms and cognitive impairments are associated with decreased cortical dopamine function. However, recent evidence suggests broader involvement of serotonergic, glutamatergic and other neurotransmitter systems and a growing body of evidence supports a role for nicotinic cholinergic systems. Based on post-mortem studies, there is a decreased density of neuronal nicotinic receptors (NNRs), especially the alpha7 NNR subtype, in the brains of schizophrenics. The alpha7 NNR subtype is the most abundant in the mammalian brain and has been shown to modulate multiple neuronal pathways that are compromised in schizophrenia, including dopaminergic, serotonergic, glutamatergic and GABAergic pathways. Familial linkage studies have associated regions of chromosome 15, which contains the alpha7 NNR gene, with schizophrenia and polymorphisms have been described in the promoter region of the alpha7 NNR gene. Observations from both animal and human studies that alpha7 NNR agonists can improve positive and negative symptoms as well as cognition to varying degrees further support the involvement of this receptor subtype in multiple deficits of schizophrenia and suggest that it may be feasible to develop novel therapies targeting alpha7 NNRs to treat all domains of the disease.

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“…As gestational choline supplementation enhances gating and cognition in adult offspring mice (Meck and Williams 2003;Stevens et al 2008Stevens et al , 2014 and increases rates of efficient sensory inhibition (P50 suppression) in human infants whose mothers' diets during pregnancy were supplemented with choline (Ross et al 2013), dietary choline supplementation has been promoted as a possible preventive intervention for cognitive deficits in individuals considered to be "at risk" for SZ (Corriveau and Glenn 2012;Freedman 2014). …”

Section: Introductionmentioning

confidence: 99%

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

Knott

Impey

Choueiry

et al. 2015

Neuropsychiatr Electrophysiol

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Background: Alpha 7 nicotinic acetylcholine receptors (α7 nAChR) are prioritized molecular targets for the development of new pharmacological treatments for impaired cognition in schizophrenia. The use of schizophrenia-associated biomarkers both as endpoints and for segmentation of homogeneous populations for early detection of cognitive enhancing agents has been advanced to enhance the drug discovery process. Methods: In this study, the mismatch negativity (MMN) event-related brain potential (ERP), considered one of the few fully developed biomarkers in schizophrenia, was employed: a) to stratify 24 healthy volunteers into subgroups exhibiting low, medium, or high auditory sensory discrimination based on pre-attentive detection of deviant auditory features, and b) to assess their acute response to a low (500 mg) and moderate dose (1000 mg) of CDP-choline, a dietary supplement with selective agonist actions at α7 nAChRs.

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Permanent improvement in deficient sensory inhibition in DBA/2 mice with increased perinatal choline

Abstract: These data show that gestational choline supplementation produces permanent improvement in a deficit associated with schizophrenia and may have implications for human prenatal nutrition.

Cited by 52 publications

References 65 publications

Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

Prenatal choline availability alters the context sensitivity of Pavlovian conditioning in adult rats

Alpha7 Neuronal Nicotinic Receptors as Targets for Novel Therapies to Treat Multiple Domains of Schizophrenia

An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level

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