AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

Levenga, Josien; Wong, Helen; Milstead, Ryan; Keller, Bailey N.; LaPlante, Lauren; Hoeffer, Charles A.

doi:10.7554/elife.30640

Cited by 77 publications

(108 citation statements)

References 56 publications

(89 reference statements)

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“…The involvement of AKT signaling in LTP is well established (Bruel-Jungerman et al, 2009;Levenga et al, 2017). Indeed, the use of AKT inhibitors or ablation of Akt1 in mice impaired L-LTP, the long-lasting form of LTP whose maintenance is required for forming memories (Levenga et al, 2017). We demonstrate an LTP impairment in our ITSN1-LKO mice, suggesting that, at least in part, this may be a result of the negative effect that the lack of ITSN1-L has on the activation of AKT.…”

Section: Discussionsupporting

confidence: 49%

“…Although we demonstrated no change in MAPK/ERK signaling activity in ITSN1-LKO mice, we did find a decrease of 19% in the basal level of phosphorylated AKT in ITSN1-LKO hippocampal homogenates. The involvement of AKT signaling in LTP is well established (Bruel-Jungerman et al, 2009;Levenga et al, 2017). Indeed, the use of AKT inhibitors or ablation of Akt1 in mice impaired L-LTP, the long-lasting form of LTP whose maintenance is required for forming memories (Levenga et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…AKT1 phosphorylation is required for the expression of LTP and for regulating activity-induced protein synthesis that supports LTP (Bruel-Jungerman et al, 2009;Levenga et al, 2017). Since both LTP and hippocampal-dependent behavior were adversely affected by the loss of the ITSN1 long isoform we investigated the possibility that defects in MAPK and AKT signaling were responsible.…”

Section: Deletion Of the Itsn1 Long Isoform Had No Effect On Basal Mamentioning

confidence: 99%

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The Long Isoform of Intersectin-1 Has a Role in Learning and Memory

Malakooti

Pritchard

Chen

et al. 2020

Front. Behav. Neurosci.

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Down syndrome is caused by partial or total trisomy of chromosome 21 and is characterized by intellectual disability and other disorders. Although it is difficult to determine which of the genes over-expressed on the supernumerary chromosome contribute to a specific abnormality, one approach is to study each gene in isolation. This can be accomplished either by using an over-expression model to study increased gene dosage or a gene-deficiency model to study the biological function of the gene. Here, we extend our examination of the function of the chromosome 21 gene, ITSN1. We used mice in which the long isoform of intersectin-1 was knocked out (ITSN1-LKO) to understand how a lack of the long isoform of ITSN1 affects brain function. We examined cognitive and locomotor behavior as well as long term potentiation (LTP) and the mitogen-activated protein kinase (MAPK) and 3-kinase-C2β-AKT (AKT) cell signaling pathways. We also examined the density of dendritic spines on hippocampal pyramidal neurons. We observed that ITSN1-LKO mice had deficits in learning and long term spatial memory. They also exhibited impaired LTP, and no changes in the levels of the phosphorylated extracellular signal-regulated kinase (ERK) 1/2. The amount of phosphorylated AKT was reduced in the ITSN1-LKO hippocampus and there was a decrease in the number of apical dendritic spines in hippocampal neurons. Our data suggest that the long isoform of ITSN1 plays a part in normal learning and memory.

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Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Deletion Of the Itsn1 Long Isoform Had No Effect On Basal Mamentioning

confidence: 99%

See 1 more Smart Citation

The Long Isoform of Intersectin-1 Has a Role in Learning and Memory

Malakooti

Pritchard

Chen

et al. 2020

Front. Behav. Neurosci.

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“…Our studies revealed that AKT and ERK activation were obviously attenuated in the brain of APP/PS1 mice, indicating that LEO can mediate these rapid kinase signaling pathways. Recently, both AKT and ERK signaling has been explained to help regulate the LTP, memory and synaptic plasticity [63][64][65]. Thus, we propose that LEO mediates AKT and ERK activation in the brain, which may contribute dramatically to its effects on the LTP, synaptic plasticity and memory of APP/PS1 mice.…”

Section: Agingmentioning

confidence: 81%

Lemon essential oil ameliorates age-associated cognitive dysfunction via modulating hippocampal synaptic density and inhibiting acetylcholinesterase

Liu

Kou

et al. 2020

Aging

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The lemon essential oil (LEO), extracted from the fruit of lemon, has been used to treat multiple pathological diseases, such as diabetes, inflammation, cardiovascular diseases, depression and hepatobiliary dysfunction. The study was designed to study the effects of LEO on cognitive dysfunction induced by Alzheimer's disease (AD). We used APP/PS1 double transgene (APP/PS1) AD mice in the experiment; these mice exhibit significant deficits in synaptic density and hippocampal-dependent spatial related memory. The effects of LEO on learning and memory were examined using the Morris Water Maze (MWM) test, Novel object recognition test, and correlative indicators, including a neurotransmitter (acetylcholinesterase, AChE), a nerve growth factor (brainderived neurotrophic factor, BDNF), a postsynaptic marker (PSD95), and presynaptic markers (synapsin-1, and synaptophysin), in APP/PS1 mice. Histopathology was performed to estimate the effects of LEO on AD mice. A significantly lowered brain AChE depression in APP/PS1 and wild-type C57BL/6L (WT) mice. PSD95/ Synaptophysin, the index of synaptic density, was noticeably improved in histopathologic changes. Hence, it can be summarized that memory-enhancing activity might be associated with a reduction in the AChE levels and is elevated by BDNF, PSD95, and synaptophysin through enhancing synaptic plasticity.

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“…According to the results of the WB, the phosphorylation levels of ERK and CREB were obviously increased in the hippocampus in response to the administration of bee pollen extract. Another important molecule associated with learning and memory is Akt, which plays a role in LTP formation 41) and memory consolidation. 42) GSK-3β, a major substrate of Akt, is known to be an important regulator of neurogenesis and synaptic plasticity in the hippocampus.…”

Section: Discussionmentioning

confidence: 99%

The Ameliorating Effects of Bee Pollen on Scopolamine-Induced Cognitive Impairment in Mice

Liao

Bae

Zhang

et al. 2019

Biological & Pharmaceutical Bulletin

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Bee pollen consists of floral pollen mixed with bee secretions and nectar. It has been considered as a functional food and has different kinds of biologically active ingredients, such as flavonoids, polyphenols, phytosterols and minerals. However, its function in cognition has yet been investigated. In the present study, we investigated the ameliorating effect of bee pollen against scopolamine-caused cognitive impairment through the passive avoidance test, the Y-maze test and the Morris water maze test. In addition, Western blotting was employed to verify the effects of bee pollen on memory-related signaling molecules in the hippocampus. Bee pollen extract (100 or 300 mg/kg, per os (p.o.)) obviously reversed scopolamine-caused cognitive impairment in the passive avoidance test, ameliorated spontaneous alternation versus the scopolaminetreated group in the Y-maze test and prolonged swimming time in the target zone in the Morris water maze test. In addition, the phosphorylation levels of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), protein kinase B (Akt) and glycogen synthase kinase-3β (GSK-3β), and the expression levels of brain-derived neurotrophic factor (BDNF) and tissue plasminogen activator (tPA) in the hippocampi, were increased in response to the treatment with bee pollen extract (100 or 300 mg/kg, p.o.). These results indicated that bee pollen ameliorates cognitive impairment induced by cholinergic blockade through the enhancing conversion of proBDNF to mature BDNF by tPA, probably, through the ERK-CREB pathway or Akt-GSK-3β signaling pathway and would be a useful agent for the treatment of cognitive dysfunction.

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AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

Cited by 77 publications

References 56 publications

The Long Isoform of Intersectin-1 Has a Role in Learning and Memory

The Long Isoform of Intersectin-1 Has a Role in Learning and Memory

Lemon essential oil ameliorates age-associated cognitive dysfunction via modulating hippocampal synaptic density and inhibiting acetylcholinesterase

The Ameliorating Effects of Bee Pollen on Scopolamine-Induced Cognitive Impairment in Mice

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