Biology subjects

Jensen, V.

Publications and source records attributed to Jensen, V..

3 recordsLinked to original sources

bioRxiv2021

Impaired astrocytic Ca2+ signalling in awake Alzheimer's disease transgenic mice

Increased astrocytic Ca2+ signaling related to amyloid plaques has been shown in Alzheimers disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signalling in such mice without the confounding effects of anesthesia. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signalling in 15-months old plaque-bearing mice. This points to a potential decoupling of neuromodulatory activation and astrocytic Ca2+ activity, which may account for some of the cognitive dysfunctions observed in Alzheimers disease.

neuroscience↗

bioRxiv2021

NEIL1 and NEIL2 DNA glycosylases regulate anxiety and learning in a cooperative manner

Oxidative DNA damage in the brain has been implicated in neurodegeneration and cognitive decline. DNA glycosylases initiate base excision repair (BER), the main pathway for oxidative DNA base lesion repair. NEIL1 and NEIL3 DNA glycosylases alter cognition in mice, the role of NEIL2 remains unclear. Here, we investigate the impact of NEIL2 and its potential overlap with NEIL1 on behavior in single and double knock-out mouse models. Neil1-/-Neil2-/- mice displayed hyperactivity, reduced anxiety and improved learning. Hippocampal oxidative DNA base lesion levels were comparable between genotypes, no mutator phenotype was found. Impaired canonical repair was thus not the cause of altered behavior. Electrophysiology indicated reduced stratum oriens afferents in the hippocampal CA1 region in Neil1-/-Neil2-/-. Within CA1, NEIL1 and NEIL2 jointly regulated transcription in genes relevant for synaptic function. Thus, we postulate a cooperative function of NEIL1 and NEIL2 in genome regulation beyond canonical BER modulating memory formation and anxiety.

molecular biology↗

bioRxiv2020

Membrane Ca2+ permeability and IP3R2 dependent Ca2+-induced Ca2+ release are essential for astrocytic intracellular Ca2+ elevation upon neuronal stimulation at the mouse hippocampal CA3 - CA1 excitatory synapses

Astrocytes are intricately involved in the activity of neural circuits, however, their basic physiology of interacting with neurons remains controversial. Using dual-indicator two-photon imaging of neurons and astrocytes during stimulations of hippocampal CA3 - CA1 Schaffer collateral (Scc) excitatory synapses, we report that under physiological conditions, the increased glutamate released from the higher frequency stimulation of neurons can accelerate local astrocytic Ca2+ levels. As consequences of extracellular glutamate clearance and maintaining of astrocytic intracellular Na+ homeostasis, the increase of astrocytic membrane Ca2+ permeability via Na+/Ca2+ exchanger (NCX) reverse mode is the primary reason of eliciting astrocytic intracellular Ca2+ elevation upon neuronal stimulation. This Ca2+-induced Ca2+ release is dependent on inositol triphosphate receptor type 2 (IP3R2). In addition, ATP released from Scc excitatory synapses can contribute to this molecular mechanism of Ca2+-induced Ca2+ release in astrocytes.

neuroscience↗