Biology subjects

Kindler, D.

Publications and source records attributed to Kindler, D..

2 recordsLinked to original sources

bioRxiv2023

Multipair phase-modulated temporal interference electrical stimulation combined with fMRI.

Temporal Interference stimulation (TIS) is a promising non-invasive brain stimulation technique exploiting frequency-shifted kHz fields to modulate oscillatory neural activity without invasive procedures. While human studies suggest TIS efficacy in targeting relatively deep brain structures, recent computational modeling and animal studies indicate potential off-target stimulations via the application of standard TIS protocols. Here, we computationally optimized TIS targeting for the prefrontal cortex (PFC) in mice. Combining in vivo electrophysiological recordings, intracellular calcium dynamics with fiber photometry, and functional MRI, we confirmed TIS-induced amplitude modulation, neuronal entrainment and hemodynamic responses in the PFC, while also identifying off-target modulations. To mitigate off-target effects, we propose a novel configuration with three electrode pairs, one of which is actively phase-shifted by 180 degrees. This cancelling field significantly enhanced TIS focality, reducing off-target effects without compromising the TIS efficacy in the target area. This work effectively addresses one of TIS most critical shortcomings and opens new avenues for research and clinical applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/571679v2_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@b04067org.highwire.dtl.DTLVardef@154549aorg.highwire.dtl.DTLVardef@17e63c3org.highwire.dtl.DTLVardef@c7a341_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2019

A novel growth factor-dependent thermogenic brown adipocyte cell line from defined precursor cells

Molecular pathways regulating brown adipocyte formation and metabolism can be exploited as targets for the treatment of obesity and disorders of glucose and lipid metabolism such as type-2 diabetes. Investigations in this direction require adequate cell models for brown adipocytes and their precursors. We report the establishment of a novel clonal cell line derived from defined Lin-Sca1+ adipocyte precursors from murine interscapular brown fat. In contrast to most currently available lines, immortalization was achieved by serial passaging without viral or genetic manipulation. Instead, the media were supplemented with basic fibroblast growth factor, which was required for the maintenance of stable long-term growth and immature morphology. BATkl2 cells differentiated to adipocytes with high efficiency upon standard adipogenic induction independently of PPARg agonists and even at higher passage numbers. BATkl2 adipocytes showed readily detectable Uncoupling protein 1 (Ucp1) protein expression and acutely responded to norepinephrine with increased Ucp1 mRNA expression, lipolysis and uncoupled mitochondrial respiration. Highly efficient siRNA-mediated knockdown was demonstrated in the growth state as well as in differentiating adipocytes, whereas plasmid DNA transfection was achieved in immature cells. These features make the BATkl2 cell line an attractive brown (pre)-adipocyte cell model.

cell biology↗