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Alzheimer Disease: HELP
Articles by Jesper Frank Bastlund
Based on 7 articles published since 2010
(Why 7 articles?)
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Between 2010 and 2020, Jesper F. Bastlund wrote the following 7 articles about Alzheimer Disease.
 
+ Citations + Abstracts
1 Review Effects of pharmacological agents, sleep deprivation, hypoxia and transcranial magnetic stimulation on electroencephalographic rhythms in rodents: towards translational challenge models for drug discovery in Alzheimer's disease. 2013

Babiloni, Claudio / Infarinato, Francesco / Aujard, Fabienne / Bastlund, Jesper Frank / Bentivoglio, Marina / Bertini, Giuseppe / Del Percio, Claudio / Fabene, Paolo Francesco / Forloni, Gianluigi / Herrero Ezquerro, Maria Trinidad / Noè, Francesco Mattia / Pifferi, Fabien / Ros-Bernal, Francisco / Christensen, Ditte Zerlang / Dix, Sophie / Richardson, Jill C / Lamberty, Yves / Drinkenburg, Wilhelmus / Rossini, Paolo Maria. ·Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; IRCCS San Raffaele Pisana, Rome, Italy. c.babiloni@unifg.it ·Clin Neurophysiol · Pubmed #23040292.

ABSTRACT: Different kinds of challenge can alter spontaneous ongoing electroencephalographic (EEG) rhythms in animal models, thus providing paradigms to evaluate treatment effects in drug discovery. The effects of challenges represented by pharmacological agents, hypoxia, sleep deprivation and transcranial magnetic stimulation (TMS) on EEG rhythms are here reviewed to build a knowledge platform for innovative translational models for drug discovery in Alzheimer's disease (AD). It has been reported that antagonists of cholinergic neurotransmission cause synchronisation of spontaneous ongoing EEG rhythms in terms of enhanced power of EEG low frequencies and decreased power of EEG high frequencies. Acetylcholinesterase inhibitors and serotonergic drugs may restore a normal pattern of EEG desynchronisation. Sleep deprivation and hypoxia challenges have also been reported to elicit abnormal synchronisation of spontaneous ongoing EEG rhythms in rodents. The feasibility and reproducibility of TMS have been demonstrated in rodents but information on a consistent modulation of EEG after TMS manipulation is very limited. Transgenic mice over-expressing human amyloid precursor protein complementary DNAs (cDNAs) harbouring the 'Swedish' mutation and PS-1 cDNAs harbouring the A264E mutation, which recapitulate some of the pathological features of AD, exhibit alterations of spontaneous ongoing EEG rhythms at several low and high frequencies. This does not appear, however, to be a consequence of beta-amyloid deposition in the brain. The present review provides a critical evaluation of changes of spontaneous ongoing EEG rhythms due to the experimental manipulations described above, in order to stimulate the promote more adherent models fitting dynamics in humans.

2 Article Ongoing Electroencephalographic Activity Associated with Cortical Arousal in Transgenic PDAPP Mice (hAPP V717F). 2018

Del Percio, Claudio / Drinkenburg, Wilhelmus / Lopez, Susanna / Limatola, Cristina / Bastlund, Jesper F / Christensen, Ditte Z / Pedersen, Jan T / Forloni, Gianluigi / Frasca, Angelisa / Noe, Francesco M / Bentivoglio, Marina / Fabene, Paolo F / Bertini, Giuseppe / Colavito, Valeria / Dix, Sophie / Ferri, Raffaele / Bordet, Regis / Richardson, Jill C / Babiloni, Claudio. ·IRCCS SDN, Naples, Italy. · Janssen Research and Development, Pharmaceutical Companies of J&J, Turnhoutseweg 30, Beerse. Belgium. · Department of Physiology and Pharmacology, University of Rome "La Sapienza", Rome, Italy. · IRCCS Neuromed Institute, Pozzilli (IS), Italy. · H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby. Denmark. · Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy. · Department of Neurological Biomedical and Movement Sciences, University of Verona, Verona, Italy. · Eli Lilly, Erl Wood Manor, Windlesham, Surrey, United Kingdom. · Department of Neurology, IRCCS Oasi Institute for Research on Mental Retardation and Brain Aging, Troina (EN), Italy. · Department of Medical Pharmacology, University Lille -2 Nord de France, Lille, France. · GlaxoSmithKline R&D Neurotherapeutics Area UK, Gunnels Wood Road, Stevenage, Hertfordshire, United Kingdom. · IRCCS San Raffaele Pisana, Rome, Italy. ·Curr Alzheimer Res · Pubmed #28675996.

ABSTRACT: BACKGROUND: It has been shown that theta (6-10 Hz) and delta (1-6 Hz) ongoing electroencephalographic (EEG) rhythms revealed variations in the cortical arousal in C57 Wild Type (WT) mice during cage exploration (active condition) compared to awake quiet behavior (passive condition; IMI PharmaCog project, www.pharmacog.eu). OBJECTIVE: The objective was to test if these EEG rhythms might be abnormal in old PDAPP mice modeling Alzheimer's disease (AD) with a hAPP Indiana V717F mutation (They show abnormal neural transmission, cognitive deficits, and brain accumulation of Aβ1-42). METHODS: Ongoing EEG rhythms were recorded by a frontoparietal bipolar channel in 15 PDAPP and 23 WT C57 male mice (mean age of 22.8 months ±0.4 and 0.3 standard error, respectively). EEG absolute power (density) was calculated. Frequency and amplitude of individual delta and theta frequency (IDF and ITF) peaks were considered during passive and active states in the wakefulness. RESULTS: Compared with the WT group, the PDAPP group showed higher frequency of the IDF during the passive condition and lower frequency of the ITF during the active state. Furthermore, the WT but not PDAPP group showed significant changes in the frontoparietal EEG power (IDF, ITF) during active over passive state. CONCLUSION: PDAPP mice were characterized by less changes in the brain arousal during an active state as revealed by frontoparietal EEG rhythms. Future studies will have to cross-validate the present results on large animal groups, clarify the neurophysiological underpinning of the effect, and test if the disease modifying drugs against AD amyloidosis normalize those candiate EEG biomarkers in PDAPP mice.

3 Article The 5-HT 2017

Amat-Foraster, Maria / Leiser, Steven C / Herrik, Kjartan F / Richard, Nelly / Agerskov, Claus / Bundgaard, Christoffer / Bastlund, Jesper F / de Jong, Inge E M. ·Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: maaf@lundbeck.com. · Lundbeck Research USA, Inc., Paramus, NJ 07652, USA. Electronic address: stevenleiser@gmail.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: kfh@lundbeck.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: nelly-richard@hotmail.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: clsg@lundbeck.com. · Discovery DMPK, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: cbun@lundbeck.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: jfb@lundbeck.com. · Division of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: idj@lundbeck.com. ·Neuropharmacology · Pubmed #27647493.

ABSTRACT: The 5-HT

4 Article The 5-HT6 receptor antagonist idalopirdine potentiates the effects of acetylcholinesterase inhibition on neuronal network oscillations and extracellular acetylcholine levels in the rat dorsal hippocampus. 2016

Herrik, Kjartan F / Mørk, Arne / Richard, Nelly / Bundgaard, Christoffer / Bastlund, Jesper F / de Jong, Inge E M. ·Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: kfh@lundbeck.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: arm@lundbeck.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: nelly-richard@hotmail.com. · Discovery DMPK, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: cbun@lundbeck.com. · Division of Synaptic Transmission, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: jfb@lundbeck.com. · Division of Neurodegeneration, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. Electronic address: idj@lundbeck.com. ·Neuropharmacology · Pubmed #27039041.

ABSTRACT: The 5-HT6 receptor has emerged as a promising target for cognitive disorders and combining a 5-HT6 receptor antagonist with an acetylcholinesterase inhibitor (AChEI) represents a novel approach for the symptomatic treatment of Alzheimer's disease (AD). A recent phase 2 trial showed that the selective 5-HT6 receptor antagonist idalopirdine (Lu AE58054) improved cognition in patients with moderate AD on stable treatment with the AChEI donepezil. Here we investigated the effects of idalopirdine in combination with donepezil on hippocampal function using in vivo electrophysiology and microdialysis. Network oscillations in the hippocampus were recorded during electrical stimulation of the brainstem nucleus pontis oralis (nPO) in the anesthetized rat and hippocampal acetylcholine (ACh) levels were measured in the freely-moving rat. In addition, potential pharmacokinetic interactions between idalopirdine and donepezil were assessed. Idalopirdine alone did not affect hippocampal network oscillations or ACh levels. Donepezil (0.3 and 1.0 mg/kg i.v.) dose-dependently increased hippocampal theta and gamma power during nPO stimulation. Idalopirdine (2 mg/kg i.v.), administered 1 h prior to donepezil, potentiated the theta and gamma response to 0.3 mg/kg donepezil and prolonged the gamma response to 1 mg/kg donepezil. Donepezil (1.3 mg/kg s.c.) increased extracellular ACh levels in the hippocampus and this was further augmented by administration of idalopirdine (10 mg/kg p.o.) 2 h prior to donepezil. These effects could not be attributed to a pharmacokinetic interaction between the compounds. This study demonstrates that idalopirdine potentiates the effects of donepezil on two pharmacodynamic biomarkers associated with cognition, i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such potentiation could contribute to the procognitive effects of idalopirdine observed in donepezil-treated AD patients.

5 Article Hippocampal P3-like auditory event-related potentials are disrupted in a rat model of cholinergic degeneration in Alzheimer's disease: reversal by donepezil treatment. 2014

Laursen, Bettina / Mørk, Arne / Kristiansen, Uffe / Bastlund, Jesper Frank. ·H. Lundbeck A/S, Synaptic Transmission 1, Valby, Denmark Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. · H. Lundbeck A/S, Synaptic Transmission 1, Valby, Denmark. · Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. ·J Alzheimers Dis · Pubmed #25024305.

ABSTRACT: P300 (P3) event-related potentials (ERPs) have been suggested to be an endogenous marker of cognitive function and auditory oddball paradigms are frequently used to evaluate P3 ERPs in clinical settings. Deficits in P3 amplitude and latency reflect some of the neurological dysfunctions related to several psychiatric and neurological diseases, e.g., Alzheimer's disease (AD). However, only a very limited number of rodent studies have addressed the back-translational validity of the P3-like ERPs as suitable markers of cognition. Thus, the potential of rodent P3-like ERPs to predict pro-cognitive effects in humans remains to be fully validated. The current study characterizes P3-like ERPs in the 192-IgG-SAP (SAP) rat model of the cholinergic degeneration associated with AD. Following training in a combined auditory oddball and lever-press setup, rats were subjected to bilateral intracerebroventricular infusion of 1.25 μg SAP or PBS (sham lesion) and recording electrodes were implanted in hippocampal CA1. Relative to sham-lesioned rats, SAP-lesioned rats had significantly reduced amplitude of P3-like ERPs. P3 amplitude was significantly increased in SAP-treated rats following pre-treatment with 1 mg/kg donepezil. Infusion of SAP reduced the hippocampal choline acetyltransferase activity by 75%. Behaviorally defined cognitive performance was comparable between treatment groups. The present study suggests that AD-like deficits in P3-like ERPs may be mimicked by the basal forebrain cholinergic degeneration induced by SAP. SAP-lesioned rats may constitute a suitable model to test the efficacy of pro-cognitive substances in an applied experimental setup.

6 Article Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. 2014

Laursen, Bettina / Mørk, Arne / Plath, Niels / Kristiansen, Uffe / Bastlund, Jesper Frank. ·H. Lundbeck A/S, Synaptic Transmission 1, Ottiliavej 9, 2500 Valby, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. Electronic address: xbc@lundbeck.com. · H. Lundbeck A/S, Synaptic Transmission 1, Ottiliavej 9, 2500 Valby, Denmark. · Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark. ·Brain Res · Pubmed #24231553.

ABSTRACT: The Alzheimer's disease (AD) mouse model Tg2576 overexpresses an AD associated mutant variant of human APP and accumulates amyloid beta (Aβ) in an age-dependent manner. Using the selective cholinergic immunotoxin mu p75-saporin (SAP), we induced a partial basal forebrain cholinergic degeneration (BFCD) in 3 months old male Tg2576 mice to co-express cholinergic degeneration with Aβ overexpression as these characteristics constitutes key hallmarks of AD. At 9 months, SAP lesioned Tg2576 mice were cognitively impaired in two spatial paradigms addressing working memory and mid to long-term memory. Conversely, there was no deterioration of cognitive functioning in sham lesioned Tg2576 mice or wild type littermates (wt) receiving the immunotoxin. At 10 months of age, release of acetylcholine (ACh) was addressed by microdialysis in conscious mice. Scopolamine-induced increases in hippocampal ACh efflux was significantly reduced in SAP lesioned Tg2576 mice compared to sham lesioned Tg2576 mice. Intriguingly, there was no significant difference in ACh efflux between wt treatment groups. Following SAP treatment, choline acetyltransferase activity was reduced in the hippocampus and frontal cortex and the reduction was comparable between groups. Our results suggest that partial BFCD acts collectively with increased levels of Aβ to induce cognitive decline and to compromise cholinergic release. Tg2576 mice with BFCD may constitute a new and suitable AD mouse model to study the interrelations between cholinergic deficits and amsyloid deposition.

7 Article Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice. 2013

Laursen, Bettina / Mørk, Arne / Plath, Niels / Kristiansen, Uffe / Bastlund, Jesper Frank. ·H. Lundbeck A/S, Synaptic Transmission 1, Ottiliavej 9, 2500 Valby, Denmark. xbc@lundbeck.com ·Behav Brain Res · Pubmed #23178660.

ABSTRACT: Cholinergic dysfunction and deposition of plaques containing amyloid β-peptides (Aβ) are two of the characteristics of Alzheimer's disease. Here, we combine APPswe/PS1dE9 (APP/PS1) mice with the cholinergic immunotoxin mu p75-saporin (SAP) to integrate partial basal forebrain cholinergic degeneration and the neuropathology of APP/PS1 mice. By 6 months of age, APP/PS1 mice and wild type littermates (Wt) received intracerebroventricular injection of 0.6 μg SAP (lesion) or PBS (sham). Two months following surgery, APP/PS1 mice treated with SAP were significantly impaired compared to sham treated APP/PS1 mice in a behavioural paradigm addressing working memory. Conversely, the performance of Wt mice was unaffected by SAP treatment. Choline acetyltransferase activity was reduced in the hippocampus and frontal cortex following SAP treatment. The selective effect of a mild SAP lesion in APP/PS1 mice was not due to a more extensive cholinergic degeneration since the reduction in choline acetyltransferase activity was similar following SAP treatment in APP/PS1 mice and Wt. Interestingly, plaque load was significantly increased in SAP treated APP/PS1 mice relative to sham lesioned APP/PS1 mice. Additionally, APP/PS1 mice treated with SAP showed a tendency towards an increased level of soluble and insoluble Aβ1-40 and Aβ1-42 measured in brain tissue homogenate. Our results suggest that the combination of cholinergic degeneration and Aβ overexpression in the APP/PS1 mouse model results in cognitive decline and accelerated plaque burden. SAP treated APP/PS1 mice might thus constitute an improved model of Alzheimer's disease-like neuropathology and cognitive deficits compared to the conventional APP/PS1 model without selective removal of basal forebrain cholinergic neurons.