Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1

Parkinson, Pamela F.; Kannangara, Timal S.; Eadie, Brennan D.; Burgess, Braydon L.; Wellington, Cheryl L.; Christie, Brian R.

doi:10.1186/1476-511x-8-5

Cited by 11 publications

(12 citation statements)

References 11 publications

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“…Another body of literature provides strong evidence that cholesterol affects both synaptic plasticity and membrane excitability of neurons in the hippocampus (Dufour et al, 2006; Fester et al, 2009; Koudinov & Koudinova, 2001; Parkinson et al, 2009; Tanaka & Sokabe, 2012; Wang & Schreurs, 2010; Ya et al, 2012). For example, Koudinov and Koudinov (2001) showed that a cholesterol diet significantly enhanced hippocampal long term potentiation, a finding that was also noted by Dufour et al (2006).…”

Section: Discussionmentioning

confidence: 99%

“…Finally, there are a significant number of reports that cholesterol modifies the electrophysiological properties of neurons in the brain particularly the hippocampus (Dufour et al, 2006; Fester et al, 2009; Koudinov & Koudinova, 2001; Parkinson et al, 2009; Tanaka & Sokabe, 2012; Wang & Schreurs, 2010; Ya et al, 2012) and, when studied in the same animals, improves spatial maze learning (Dufour et al, 2006; Ya et al, 2012). Although most of these reports have focused on synaptic plasticity (Koudinov & Koudinova, 2001; Ya et al, 2012), Wang and Schreurs (2010) have shown that a cholesterol diet also has significant effects on the membrane properties of hippocampal neurons including reductions in the size of the afterhyperpolarization – a property that has been shown to be important for learning and memory in rodents and rabbits (Bekisz et al, 2010; Disterhoft & Oh, 2006; Kaczorowski, Sametsky, Shah, Vassar, & Disterhoft, 2009; Kuiper et al, 2012; Matthews, Weible, Shah, & Disterhoft, 2008; Moyer, Jr., Thompson, & Disterhoft, 1996; Tombaugh, Rowe, & Rose, 2005).…”

Section: Introductionmentioning

confidence: 99%

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Dietary cholesterol degrades rabbit long term memory for discrimination learning but facilitates acquisition of discrimination reversal

Schreurs¹,

Smith-Bell²,

Wang³

et al. 2013

Neurobiology of Learning and Memory

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We have shown previously that feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long term memory. To examine these different findings within a single paradigm, we fed groups of rabbits 2% cholesterol or normal chow with or without 0.12 ppm copper added to the drinking water following two-tone discrimination learning of the nictitating membrane response in which a 8-kHz tone (conditioned stimulus, CS+) was followed by air puff and a 1-kHz tone (CS−) was not. After eight weeks on the diet, we assessed the rabbits’ conditioned responding during testing and retraining. We then reversed the two-tone discrimination and assessed responding to the 1-kHz tone CS+ and the 8-kHz CS−. During testing, rabbits given cholesterol without copper had lower levels of responding to CS+ than rabbits in the other groups suggesting they did not retain the discrimination as well. However, during a brief discrimination retraining session, their response levels to the CS+ returned to the level of the other groups, demonstrating a return of the memory of the original discrimination. At the end of discrimination reversal, these same rabbits exhibited superior discrimination indexed by lower response levels to CS− but similar levels to CS+, suggesting they were better able to acquire the new relationship between the two tones by inhibiting CS− responses. These results add to our previous data by showing cholesterol diet-induced degradation of an old memory and facilitation of a new memory can both be demonstrated within a discrimination reversal paradigm. Given discrimination reversal is a hippocampally-dependent form of learning, the data support the role of cholesterol in modifying hippocampal function as we have shown previously with in vitro brain slice recordings.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dietary cholesterol degrades rabbit long term memory for discrimination learning but facilitates acquisition of discrimination reversal

Schreurs¹,

Smith-Bell²,

Wang³

et al. 2013

Neurobiology of Learning and Memory

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“…There are two studies of learning and memory in transgenic mice over-expressing ABCG1 from different groups and both failed to find any effects of ABCG1 on water maze acquisition or retention (Burgess et al ., 2008; Parkinson et al ., 2009). Perhaps like ABCA1, ABCG1 may only have an effect when learning and memory are already compromised as in the human studies of dementia and the Lefterov et al (2009) study of APP transgenic mice.…”

Section: Atp Binding Cassette Transportersmentioning

confidence: 99%

The effects of cholesterol on learning and memory

Schreurs

2010

Neuroscience & Biobehavioral Reviews

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Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, proinflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.

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“…Cholesterol loading in vitro enhances ABCG1, but not ABCA1, expression and correlates best with cholesterol efflux from astrocytes (Karten et al, 2006). While difficult to reconcile, the in vivo and in vitro discrepancies still point to some common features: ABCG1 over-expression does not influence cognition, learning and memory, nor hippocampal synaptic plasticity (Parkinson et al, 2009), nor ABCA1 or apoE levels (Burgess et al, 2008a(Burgess et al, , 2008b in transgenic mice; suggesting a rather modest contribution of ABCG1, if any, in lipid mobilization and in the maintenance of synaptic integrity or plasticity in the adult brain.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment

et al. 2014

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Entorhinal cortex lesioning (ECL) causes an extensive deafferentation of the hippocampus that is classically followed by a compensatory reinnervation, where apolipoprotein E, the main extracellular lipid-carrier in the CNS, has been shown to play a crucial role by shuttling cholesterol to reconstructing neurons terminals. Hence, we investigated whether the ATP-binding cassette (ABC) transporters -A1 and -G1, known to regulate cellular cholesterol efflux and lipidation of the apolipoprotein E-containing lipoprotein complex are actively involved in this context of brain's plastic response to neurodegeneration and deafferentation. We assessed ABCA1 and ABCG1 mRNA and protein levels throughout the degenerative phase and the reinnervation process and evaluated the associated cholinergic sprouting following ECL in the adult mouse brain. We subsequently tested the effect of the pharmacological activation of the nuclear receptor LXR, prior to versus after ECL, on hippocampal ABCA1 and G1 expression and on reinnervation.ECL induced a time-dependent up-regulation of ABCA1, but not G1, that coincided with a significant increase in acetylcholine esterase (AChE) activity in the ipsilateral hippocampus. Pre-ECL, but not post-ECL i.p. treatment with the LXR agonist TO901317 also led to a significant increase solely in hippocampal ABCA1 expression, paralleled by increases in both AchE and synaptophysin protein levels in the deafferented hippocampus. Thus, ABCA1 and -G1

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Cognition, learning behaviour and hippocampal synaptic plasticity are not disrupted in mice over-expressing the cholesterol transporter ABCG1

Cited by 11 publications

References 11 publications

Dietary cholesterol degrades rabbit long term memory for discrimination learning but facilitates acquisition of discrimination reversal

Dietary cholesterol degrades rabbit long term memory for discrimination learning but facilitates acquisition of discrimination reversal

The effects of cholesterol on learning and memory

Differential regulation of ABCA1 and ABCG1 gene expressions in the remodeling mouse hippocampus after entorhinal cortex lesion and liver-X receptor agonist treatment

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