Biology subjects

Keimpema, E.

Publications and source records attributed to Keimpema, E..

3 recordsLinked to original sources

bioRxiv2026

Astrocytes modulate mitochondrial proteostasis and membrane potential in neurons through S100A6 - calcyclin-binding protein signaling

Calcyclin binding protein (CaCyBp) is an evolutionarily conserved protein that converts S100 protein family-derived signals to protein turnover through an ubiquitin ligase interaction domain within its C-terminus. Despite its predicted roles in cellular differentiation, CaCyBp expression alone and in relation to S100A6, its prototypic ligand, during fetal and postnatal organ development remains incompletely understood. Here, we combined cell-resolved neuroanatomy and biochemistry to reveal not only organ system-level CaCyBp expression but also its region-, circuit-, and neuron-specific distribution in the mouse brain from embryonic day 18.5. We extended these studies to human brains past gestational week 27, corroborating that neurons, but not astrocytes, microglia or oligodendrocytes, harbored CaCyBp. Conversely, S100A6 was detected only in astrocytes and ependymoglia in both species. Ultrastructural studies localized CaCyBp to mitochondria in neurons, with genetic loss-of-function and recombinant S100A6-induced signaling implicating CaCyBp in the regulation of the mitochondrial electrochemical gradient controlling ATP production. Overall, pleiotropic CaCyBp expression in neurons suggests a maintenance receptor-like role impacting cellular respiration, thus affecting proteostasis upon glia-derived S100A6 signals.

cell biology↗

bioRxiv2025

(S)-ketamine augments behavioral and physiological responses to Δ9-tetrahydrocannabinol

(S)-ketamine is a fast-acting therapeutic to manage treatment-resistant depression as well as psychiatric emergencies. As the non-prescribed use of ketamine has rapidly increased over the past decade, its possible interactions with other recreational drugs are of increasing interest. Here, we addressed if {Delta}9-tetrahydrocannabinol (THC), the main psychoactive constituent of Cannabis sp., and (S)-ketamine could affect each others psychoactive profile in a pharmacological triad. In healthy male mice, the sequential use of (S)-ketamine followed by THC at human-relevant doses did not result in either synergistic or antagonistic effects acutely. In contrast, THC-induced hypothermia was nearly doubled by subsequent (S)-ketamine administration. THC-induced hypolocomotion was not only prolonged by (S)-ketamine, but axial rotation and stumbling during ambulation in an open field were increased in subjects exposed sequentially to both drugs. Likewise, the performance of subjects exposed to THC and then (S)-ketamine worsened on a rotarod. Combined drug treatment led to unusual epinephrine and corticosterone profiles in blood plasma. We suggest that (S)-ketamine augments adverse THC effects, which at the endocrine level invoke the acute deregulation of the hypothalamus-pituitary-adrenal axis. Our findings support the clinical notion that combining cannabis and (S)-ketamine should be avoided.

pharmacology and toxicology↗

bioRxiv2023

Astrocytes modulate neuronal development by S100A6 signaling

Neuronal morphogenesis relies on intercellular signaling. Astrocytes release metabolites, trophic, and guidance factors to promote neuronal maturation. In contrast, the mechanisms by which astrocytes could limit and stabilize neuronal connectivity remain less explored. Here, we show cortical astrocytes to express and release S100A6, a Ca2+-binding protein ( calcyclin). Simultaneously, the majority of cortical neurons express calcyclin-binding protein (CaCyBp), a bona fide binding partner for S100A6. In neurons, CaCyBp maintains the unfolded protein response pathway, thereby controlling proteostasis. When released, S100A6 inhibits CaCyBp-mediated signaling, thus slowing protein turnover, and, consequently, neuritogenesis. S100A6-CaCyBp signaling during gestation and lactation is sensitive to the mothers nutritional status, particularly eicosapentaenoic acid intake. Thus, a member of the S100 protein family acts as an astroglia-derived morphogen, whose action on neurons is modulated by environmental factors.

neuroscience↗