Biology subjects

Hagenacker, T.

Publications and source records attributed to Hagenacker, T..

3 recordsLinked to original sources

bioRxiv2026

Age-dependent peripheral nerve and Schwann cell abnormalities in a mouse model of late-onset spinal muscular atrophy

Spinal muscular atrophy (SMA) is increasingly recognized as a multisystem disorder involving non-neuronal cells, yet the role of Schwann cells (SCs) in late-onset SMA (loSMA) remains unclear. We investigated age-dependent peripheral nerve pathology in a four-copy SMN2 mouse model of loSMA. Sciatic nerves from wild-type and loSMA mice were analyzed at postnatal (P) days 20, 35, 70, and >100 using semi-thin morphometry, immunofluorescence for MBP, Sox10, Sox2, and F4/80, and nerve conduction studies. loSMA nerves showed reduced myelin thickness at all time points and smaller axon diameters at P20 and P35. G- ratios were reduced at P20 but increased from P35 onward, indicating progressively altered axon-myelin relationships. MBP immunofluorescence intensity, compound muscle action potential amplitude, and nerve conduction velocity were reduced in loSMA mice at P>100. The proportion of Sox2+ SCs increased from P35 onward, while Sox10+ cell abundance increased at later stages. F4/80+ macrophages were transiently elevated at P35 and correlated with Sox2+ cell numbers at this stage. These findings demonstrate age-dependent myelin abnormalities, altered SC states, and transient accumulation of macrophages in loSMA peripheral nerves. Whether these changes are SC-autonomous or secondary to chronic axonal dysfunction remains to be determined.

neuroscience↗

bioRxiv2025

Sustained learned immunosuppression could not prevent local allergic ear swelling in a rat model of contact hypersensitivity

Taste-immune associative learning has been shown to mimic immunopharmacological responses. Conditioned pharmacological effects may therefore be considered as controlled drug dose reduction strategy to maintain treatment efficacy. Against this background, the present study applied an established taste-immune associative learning protocol to a rat model of hapten-induced contact hypersensitivity. After repeated pairings of a saccharin taste (conditioned stimulus, CS) with injections of the immunosuppressant cyclosporine A (CsA, unconditioned stimulus, UCS), animals were sensitized with the hapten. Retrieval started by presenting the CS together with sub-effective doses of CsA. This procedure preserved a conditioned suppression of splenic cytokine production. Compared to full dose treated animals, conditioned effects were neither observed in draining lymph nodes nor did it prevent ear swelling. These findings suggest that local allergic reactions in sensitized animals were most likely too strong to be responsive to the learned immunosuppressive effects. Additionally, symptoms such as itch may be more suited as readout parameter since it better reflects patients disease burden. The present study reaffirms that learned immunopharmacological effects can be preserved using a memory-updating approach. It also emphasizes the need to further explore the usability of associative learning protocols in clinical contexts in order to address disease-specific symptoms more effectively.

animal behavior and cognition↗

bioRxiv2023

Post-ischemic triiodothyronine treatment improves stroke outcome by stabilizing the blood-brain barrier

Thyroid hormones control a variety of processes in the central nervous system and influence its response to different stimuli, such as ischemic stroke. Post-stroke administration of triiodothyronine (T3) has been reported to substantially improve outcomes, but the optimal dosage and time window remain elusive. To this end we investigated the consequences of T3 treatment in an experimental model of ischemic stroke in mice. Our research demonstrated a dose-dependent protective effect of T3 by reducing infarct volumes, with the optimal T3 dosage identified as 25 {micro}g/kg. In addition, we observed a time-dependent effectiveness that was most pronounced when T3 was administered 1 h after transient middle cerebral artery occlusion, with a gradual reduction in efficacy at 4.5 h, and no reduction in infarct volumes when T3 was injected with an 8 h delay. This protective effect persisted for 72 h post-tMCAO, and had accelerated the recovery of motor function by day 3. In-depth investigations further revealed stabilization of the blood-brain barrier, indicated by reduced extravasation of Evans Blue and diminished aquaporin-4 expression, with reduced inflammation and less cell death as underlying reasons. Our findings suggest that thyroid hormones may be a promising intervention for clinical stroke.

neuroscience↗