An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

Kempf, Stefan J.; Metaxas, Athanasios; Ibáñez-Vea, María; Darvesh, Sultan; Finsen, Bente; Larsen, Martin R.

doi:10.18632/oncotarget.9092

Cited by 41 publications

(32 citation statements)

References 70 publications

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“…Another important caveat is that Aβ overproducing mice used in the present study have relatively limited p-Tau pathology (Kempf et al, 2016; Roberson et al, 2007). Despite the lack of p-Tau accumulation in these models, reduction of total Tau protects against hyperactive behavior (Roberson et al, 2007).…”

Section: Discussionmentioning

confidence: 97%

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

Krivinko

Erickson

Abrahamson

et al. 2017

Neurobiology of Aging

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Psychosis in Alzheimer disease (AD+P) represents a distinct clinical and neurobiological AD phenotype, and is associated with more rapid cognitive decline, higher rates of abnormal behaviors, and increased caregiver burden compared to AD without psychosis. On a molecular level, AD+P is associated with greater reductions in the protein kalirin, a guanine exchange factor which has also been linked to the psychotic disease, schizophrenia. In this study, we sought to determine the molecular and behavioral consequences of kalirin reduction in APPswe/PSEN1dE9 mice. We evaluated mice with and without kalirin reduction during tasks measuring psychosis-associated behaviors and spatial memory. We found that kalirin reduction in APPswe/PSEN1dE9 mice significantly attenuated psychosis-associated behavior at 12 months of age without changing spatial memory performance. The 12 month old APPswe/PSEN1dE9 mice with reduced kalirin levels also had increased levels of the active, phosphorylated form of p21 protein (Cdc42/Rac)-activated kinases (PAKs), which function in signaling pathways for maintenance of dendritic spine density, morphology, and function.

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Section: Discussionmentioning

confidence: 97%

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

Krivinko

Erickson

Abrahamson

et al. 2017

Neurobiology of Aging

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“…Several genetic mouse models of AD that display amyloid pathology, for example APP/PS1 mice [41], display impairments in spatial-cognitive tasks such as radial-arm water maze or MWM [42].…”

Section: Discussionmentioning

confidence: 99%

Subtle behavioral changes and increased prefrontal-hippocampal network synchronicity in APPNL−G−F mice before prominent plaque deposition

Latif‐Hernandez

Shah

Craessaerts

et al. 2019

Behavioural Brain Research

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Amyloid-β (Aβ) peptides occur in the brains of patients with Alzheimer's disease (AD), but their role in functional impairment is still debated. High levels of APP and APP fragments in mice that overexpress APP might confound their use in preclinical research. We examined the occurrence of behavioral, cognitive and neuroimaging changes in APP knock-in mice that display Aβ42 amyloidosis in the absence of APP overexpression. Female APP mice (carrying Swedish, Iberian and Arctic APP mutations) were compared to APP mice (APP Swedish) at 3, 7 and 10 months. Mice were subjected to a test battery that referred to clinical AD symptoms, comprising cage activity, open field, elevated plus maze, social preference and novelty test, and spatial learning, reversal learning and spatial reference memory performance. Our assessment confirmed that behavior at these early ages was largely unaffected in these mice in accordance with previous reports, with some subtle behavioral changes, mainly in social and anxiety-related test performance. Resting-state functional MRI (rsfMRI) assessed connectivity between hippocampal and prefrontal regions with an established role in flexibility, learning and memory. Increased prefrontal-hippocampal network synchronicity was found in 3-month-old APP mice. These functional changes occurred before prominent amyloid plaque deposition.

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“…Prolonged ketamine exposure in neonates at anesthetic doses has been reported to cause long-term impairments of learning and memory [20]. Furthermore, ketamine decreased p-CREB in the hippocampus [21, 22], and decreased levels of BDNF [23]. CREB has been demonstrated to be involved in learning and memory deficits caused by ketamine [10, 22].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, ketamine decreased p-CREB in the hippocampus [21, 22], and decreased levels of BDNF [23]. CREB has been demonstrated to be involved in learning and memory deficits caused by ketamine [10, 22]. These findings raise concern about potential adverse effects of ketamine exposure to fetuses and infants.…”

Section: Discussionmentioning

confidence: 99%

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

Guo

et al. 2017

Oncotarget

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Ketamine has been reported to impair the capacity for learning and memory. This study examined whether these capacities were also altered in the offspring and investigated the role of the CREB signaling pathway in pregnant rats, subjected to ketamine-induced anesthesia. On the 14th day of gestation (P14), female rats were anesthetized for 3 h via intravenous ketamine injection (200 mg/Kg). Morris water maze task, contextual and cued fear conditioning, and olfactory tasks were executed between the 25th to 30th day after birth (B25-30) on rat pups, and rats were sacrificed on B30. Nerve density and dendritic spine density were examined via Nissl’s and Golgi staining. Simultaneously, the contents of Ca2+/Calmodulin-Dependent Protein Kinase II (CaMKII), p-CaMKII, CaMKIV, p-CaMKIV, Extracellular Regulated Protein Kinases (ERK), p-ERK, Protein Kinase A (PKA), p-PKA, cAMP-Response Element Binding Protein (CREB), p-CREB, and Brain Derived Neurotrophic Factor (BDNF) were detected in the hippocampus. We pretreated PC12 cells with both PKA inhibitor (H89) and ERK inhibitor (SCH772984), thus detecting levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. The results revealed that ketamine impaired the learning ability and spatial as well as conditioned memory in the offspring, and significantly decreased the protein levels of ERK, p-ERK, PKA, p-PKA, p-CREB, and BDNF. We found that ERK and PKA (but not CaMKII or CaMKIV) have the ability to regulate the CREB-BDNF pathway during ketamine-induced anesthesia in pregnant rats. Furthermore, ERK and PKA are mutually compensatory for the regulation of the CREB-BDNF pathway.

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An integrated proteomics approach shows synaptic plasticity changes in an APP/PS1 Alzheimer's mouse model

Cited by 41 publications

References 70 publications

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

Kalirin reduction rescues psychosis-associated behavioral deficits in APPswe/PSEN1dE9 transgenic mice

Subtle behavioral changes and increased prefrontal-hippocampal network synchronicity in APPNL−G−F mice before prominent plaque deposition

Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway

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