Motor Cortex Theta and Gamma Architecture in Young Adult APPswePS1dE9 Alzheimer Mice

Papazoglou, Anna; Soós, Julien; Lundt, Andreas; Wormuth, Carola; Ginde, Varun Raj; Müller, Ralf; Henseler, Christina; Broich, Karl; Xie, Keliang; Haenisch, Britta; Ehninger, Dan; Weiergräber, Marco

doi:10.1371/journal.pone.0169654

Cited by 9 publications

(16 citation statements)

References 59 publications

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“…A second 24 h long-term baseline recording (R2) was conducted at day 17 post implantation to check whether potential alterations in relative EEG frequency range power are robust over time or whether there are developmental changes 96 – 98 (Fig. 1 A).…”

Section: Methodsmentioning

confidence: 99%

Enhanced hippocampal type II theta activity AND altered theta architecture in mice lacking the Cav3.2 T-type voltage-gated calcium channel

Arshaad

Siwek

Henseler

et al. 2021

Sci Rep

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T-type Ca2+ channels are assumed to contribute to hippocampal theta oscillations. We used implantable video-EEG radiotelemetry and qPCR to unravel the role of Cav3.2 Ca2+ channels in hippocampal theta genesis. Frequency analysis of spontaneous long-term recordings in controls and Cav3.2−/− mice revealed robust increase in relative power in the theta (4–8 Hz) and theta-alpha (4–12 Hz) ranges, which was most prominent during the inactive stages of the dark cycles. Urethane injection experiments also showed enhanced type II theta activity and altered theta architecture following Cav3.2 ablation. Next, gene candidates from hippocampal transcriptome analysis of control and Cav3.2−/− mice were evaluated using qPCR. Dynein light chain Tctex-Type 1 (Dynlt1b) was significantly reduced in Cav3.2−/− mice. Furthermore, a significant reduction of GABA A receptor δ subunits and GABA B1 receptor subunits was observed in the septohippocampal GABAergic system. Our results demonstrate that ablation of Cav3.2 significantly alters type II theta activity and theta architecture. Transcriptional changes in synaptic transporter proteins and GABA receptors might be functionally linked to the electrophysiological phenotype.

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Section: Methodsmentioning

confidence: 99%

Enhanced hippocampal type II theta activity AND altered theta architecture in mice lacking the Cav3.2 T-type voltage-gated calcium channel

Arshaad

Siwek

Henseler

et al. 2021

Sci Rep

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“…Note that the 10 day recovery period is based on the observation that 10 days post surgery no differences in physiological parameters between transmitter implanted, non-implanted, and sham-operated animals could be detected [6] , [7] . The second 24 h long-term baseline recording (R2) was conducted at day 17 post implantation to check whether relative EEG power frequency values for the different frequency bands are robust over time [8] , [9] , [10] . In addition, at day 18 and 25 post implantation two EEG recordings were carried out following urethane injections (U1, U2) with 800 mg/kg i.p.…”

Section: Experimental Design Materials and Methodsmentioning

confidence: 99%

Spontaneous long-term and urethane induced hippocampal EEG power, activity and temperature data from mice lacking the Cav3.2 voltage-gated Ca2+ channel

et al. 2021

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This article provides raw relative electroencephalographic (EEG) power, temperature and activity data from controls and Ca v 3.2 deficient mice. Radiotransmitter implantation was carried out in male experimental mice under ketamine/xylazine narcosis. Following a recovery period, radiotelemetric EEG recordings from the hippocampal CA1 region were obtained under spontaneous 24 h long-term conditions and post urethane injection. Relative EEG power values (%) for 2 s epochs were analysed for the following frequency ranges: delta 1 ( , 0.5–4 Hz), delta 2 ( , 1–4 Hz), theta 1 ( , 4–8 Hz), theta 2 ( , 4–12 Hz), alpha ( , 8–12 Hz), sigma ( , 12–16 Hz), beta 1 ( , 12–30 Hz), beta 2 ( , 16–24 Hz), beta 3 ( , 16–30 Hz), gamma low ( , 30–50 Hz), gamma mid ( , 50–70 Hz), gamma high ( , 70–100 Hz), gamma ripples ( , 80–200 Hz), and gamma fast ripples ( , 200–500 Hz). In addition, subcutaneous temperature and relative activity data were analysed for both the light and dark cycle of two long-term recordings. The same type of data was obtained post urethane injection. Detailed information is provided for the age and body weight of the experimental animals, the technical specifications of the radiofrequency transmitter, the stereotaxic coordinates for the intracerebral, deep and epidural, surface EEG electrodes, the electrode features, the filtering and sampling characteristics, the analysed EEG frequency bands and the data acquisition parameters. EEG power data, temperature and activity data are available at MENDELEY DATA (doi: 10.17632/x53km5sby6.1 , URL: http://dx.doi.org/10.17632/x53km5sby6.1 ). Raw EEG data are available at zenodo ( https://zenodo.org/ ).

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“…In our study, an APPswePS1dE9 (APP/PS1) AD mouse model has been utilized, carrying the human APP with Swedish double mutation (APPswe) co-integrated with human PS1 with exon 9 deletion (PS1dE9) [ 11 – 14 , 27 , 28 ]. These mutations result in an overproduction of APP and PS1 splice variants and a subsequent neural Aβ overload.…”

Section: Introductionmentioning

confidence: 99%

“…Cognitive/memory impairment and behavioral deficits observed, e.g., in spatial navigation tasks, reference learning, Morris’ water maze and radial arm maze, become obvious at an age of 6 to 12 months of age [ 30 ]. Furthermore, seizure activity is often encountered in AD mouse mutants including APP/PS1 and intracerebral Aβ accumulation was shown to be linked to epileptogenesis [ 13 , 14 , 31 , 32 ]. Thus, seizure activity might be responsible for sudden death in this mouse line as well [ 31 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

“…We previously demonstrated that neurodegenerative alterations in the motor cortex and septohippocampal system of APP/PS1 mice (but also in other AD lines such as 5XFAD) can result in complex central dysrhythmia [ 32 ], particularly in the theta (4–8 Hz) and two distinct gamma frequency ranges (30–50 Hz and 50–70 Hz) [ 13 , 14 ]. Importantly, these systemic in vivo macro-scale electrophysiological findings in the electrocorticogram (ECoG) and electrohippocampogram (EHipG) of APP/PS1 mice, turned out to be clearly age-, sex- and brain region-specific and demonstrated that subgroup-specific analysis in AD research is indispensable [ 13 , 14 ]. The latter has substantial implications for AD drug research and development and individualized/personalized pharmacological AD treatment.…”

Section: Introductionmentioning

confidence: 99%

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Sex- and region-specific cortical and hippocampal whole genome transcriptome profiles from control and APP/PS1 Alzheimer’s disease mice

Papazoglou,

Henseler,

Weickhardt

et al. 2024

PLoS ONE

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A variety of Alzheimer’s disease (AD) mouse models has been established and characterized within the last decades. To get an integrative view of the sophisticated etiopathogenesis of AD, whole genome transcriptome studies turned out to be indispensable. Here we carried out microarray data collection based on RNA extracted from the retrosplenial cortex and hippocampus of age-matched, eight months old male and female APP/PS1 AD mice and control animals to perform sex- and brain region specific analysis of transcriptome profiles. The results of our studies reveal novel, detailed insight into differentially expressed signature genes and related fold changes in the individual APP/PS1 subgroups. Gene ontology and Venn analysis unmasked that intersectional, upregulated genes were predominantly involved in, e.g., activation of microglial, astrocytic and neutrophilic cells, innate immune response/immune effector response, neuroinflammation, phagosome/proteasome activation, and synaptic transmission. The number of (intersectional) downregulated genes was substantially less in the different subgroups and related GO categories included, e.g., the synaptic vesicle docking/fusion machinery, synaptic transmission, rRNA processing, ubiquitination, proteasome degradation, histone modification and cellular senescence. Importantly, this is the first study to systematically unravel sex- and brain region-specific transcriptome fingerprints/signature genes in APP/PS1 mice. The latter will be of central relevance in future preclinical and clinical AD related studies, biomarker characterization and personalized medicinal approaches.

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Motor Cortex Theta and Gamma Architecture in Young Adult APPswePS1dE9 Alzheimer Mice

Cited by 9 publications

References 59 publications

Enhanced hippocampal type II theta activity AND altered theta architecture in mice lacking the Cav3.2 T-type voltage-gated calcium channel

Enhanced hippocampal type II theta activity AND altered theta architecture in mice lacking the Cav3.2 T-type voltage-gated calcium channel

Spontaneous long-term and urethane induced hippocampal EEG power, activity and temperature data from mice lacking the Cav3.2 voltage-gated Ca2+ channel

Sex- and region-specific cortical and hippocampal whole genome transcriptome profiles from control and APP/PS1 Alzheimer’s disease mice

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