A Within-Subject Experimental Design using an Object Location Task in Rats

Bayraktar, Gülberk; Højgaard, Kristoffer; Nijssen, Luc; Takeuchi, Tomonori

doi:10.3791/62458

“…The test relies on three sessions: habituation session (T0), training session (T1), and test session (T2). The test had been carried out as described by [ 6 , 30 ] in an open-field apparatus (50 * 50 *30 cm 3 ). At the training session, two identical items (A, A) had been positioned at a constant distance within the apparatus.…”

Section: Methodsmentioning

confidence: 99%

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model

Moghazy,

Abdelhaliem,

Mohammed

et al. 2024

Pflugers Arch - Eur J Physiol

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The American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-β deposition, glycogen synthase kinase 3 beta (GSK3β), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3β/TTBK pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10 weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200 μg/kg/day sc) or liraglutide (0.6 mg/kg/day sc) for 6 weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3β/TTBK expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.

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“…We identi ed 10 genes with signi cantly altered expression, whose proteins are predominantly found in postsynaptic dendritic spines: 9 genes exhibited upregulated transcription levels, while 1 gene demonstrated downregulated expression. Second, we established a novel environment for rats suitable for enhancing spatial memory encoded during the object location paradigm (47). Notably, the enhancement of novelty-induced spatial memory was inhibited by treatment with the dopamine D 1 /D 5 receptor antagonist, SCH 23390.…”

Section: Discussionmentioning

confidence: 99%

“…The object location task used here is a modi ed version from Bayraktar et al (47). For the behavioral experiments 93 animals from 4 different cohorts were used.…”

Section: Object Location Memory Taskmentioning

confidence: 99%

“…Memory is measured by the preference for exploring the object that has been moved. Based on our previously published paper (47), behavioural batch 1 (n = 8/group) was trained using a weak encoding protocol (20-min encoding) for which memory decays over time to investigate the effects of post-encoding novelty exploration on memory retention. Rats were given weak encoding, and after a 40-min period, they were either allowed to explore a novel environment for 5 min (experimental group) or remained in their home-cages as usual (control group).…”

Section: Contextual Novelty-induced Transcriptional Changes In the Mo...mentioning

confidence: 99%

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Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

Højgaard

¹

,

Szöllősi

²

,

Henningsen

³

et al. 2023

Preprint

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Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role for Agap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription of Agap3 may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5 receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.

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“…The object location task used here is a modified version from Bayraktar et al [ 44 ]. For the behavioral experiments 93 animals from 4 different cohorts were used.…”

Section: Methodsmentioning

confidence: 99%

Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

Højgaard,

Szöllősi,

Henningsen

et al. 2023

Mol Brain

0

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Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role for Agap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription of Agap3 may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5 receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.

show abstract

A Within-Subject Experimental Design using an Object Location Task in Rats

Cited by 5 publications

References 0 publications

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model

Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

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