Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.11.19.389452

Genetic and pharmacological manipulations of glyoxalase 1 mediate ethanol withdrawal seizure susceptibility in mice

Barkley-Levenson, A. M.·Lee, A.·Palmer, A. A.
View original source ↗Export metadata ↓

Abstract

Central nervous system (CNS) hyperexcitability is a clinically significant feature of acute ethanol withdrawal. There is evidence for a genetic contribution to withdrawal severity, but specific genetic risk factors have not be identified. The gene glyoxalase 1 (Glo1) has been previously implicated in ethanol consumption in mice, and GLO1 inhibition can attenuate drinking in mice and rats. Here, we investigated whether genetic and pharmacological manipulations of GLO1 activity can also mediate ethanol withdrawal seizure severity in mice. Mice from two transgenic lines overexpressing Glo1 on different genetic backgrounds (C57BL/6J [B6] and FVB/NJ [FVB]) were tested for handling induced convulsions (HICs) as a measure of acute ethanol withdrawal. Following an injection of 4 g/kg alcohol, both B6 and FVB mice overexpressing Glo1 showed increased HICs compared to wild type littermates, though only the FVB line showed a statistically significant difference. We also administered daily ethanol injections (2 g/kg + 9 mg/kg 4-methylpyrazole) to wild type B6 mice for 10 days and tested them for HICs on the 10th day, following treatment with either vehicle or a GLO1 inhibitor (S-bromobenzylglutathione cyclopentyl diester [pBBG]). Treatment with pBBG reduced HICs, although this effect was only statistically significant following two 10-day cycles of ethanol exposure and withdrawal. These results provide converging genetic and pharmacological evidence that GLO1 can mediate ethanol withdrawal seizure susceptibility. We discuss the possible role of GLO1s substrate, methylglyoxal, acting as an agonist at GABAA receptors.

Source connections

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Barkley-Levenson, A. M., Lee, A., Palmer, A. A.. 2020-11-19. Genetic and pharmacological manipulations of glyoxalase 1 mediate ethanol withdrawal seizure susceptibility in mice. https://doi.org/10.1101/2020.11.19.389452

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Same Movements, Different Skills: How Context Shapes Learning in Humans and Neural Networks

What determines whether experiences are integrated into shared representations or split? Motor skill learning offers a revealing test: when two tasks require an identical sequence of movements, both intuition and theory suggest that practice in one should generalize to the other. Yet we find that changing context can make identical movements different skills. In simple recurrent networks trained on the same sequence across contexts, splitting was greatest when strong contextual inputs coincided with a high initial weight scale; neither alone sufficed. Greater representational separation coincided with separate context-specific learning curves. Humans practicing the same finger sequence while alternating between two performance-irrelevant contexts likewise exhibited context-specific curves, rather than the single continuous trajectory observed when practicing in a single context. State-space modeling favored split learning states in humans and very weakly coupled states in the most context-dependent networks. These findings have broader implications for understanding how learning generalizes across contexts.

neuroscience↗
bioRxiv2026

Postpartum resource scarcity reshapes maternal care, offspring prioritization, and the steroid-sensitive medial preoptic area

Parental care requires balancing offspring needs with environmental constraints, yet how resource scarcity alters the organization of maternal responses remains poorly understood. Here, we examined maternal behavior, offspring prioritization, and steroid receptor-associated extracellular matrix organization in postpartum rats exposed to limited bedding and nesting (LBN) or control conditions with ample nesting materials. LBN increased pup-directed and reduced self-directed behaviors but also increased behavioral entropy, a measure of behavioral fragmentation, indicating less predictable caregiving sequences. LBN dams preferentially retrieved male pups first, whereas control dams preferentially retrieved females first. LBN also increased the proportion of pup-investigation time directed toward males compared with controls. In offspring on postnatal day 10, corticosterone was elevated in female but not male LBN pups, a pattern that paralleled the maternal male bias. To identify associated neurobiological changes, we assessed steroid receptors and extracellular matrix organization in the medial preoptic area (mPOA), a key region for maternal behavior. LBN increased numbers of estrogen receptor (ER)- and androgen receptor (AR)-immunoreactive cells, reduced perineuronal net (PNN) abundance, and decreased receptor-positive cell enwrapment. Because PNNs constrain structural plasticity, these findings suggest that the postpartum environment alters the organization of steroid receptor-associated extracellular matrix, potentially modulating experience-dependent plasticity in neurosteroid-sensitive circuits. In sum, LBN increases the levels of maternal engagement while reshaping its temporal organization and allocation, accompanied by selective remodeling of steroid-sensitive preoptic architecture. Therefore, maternal adaptation to adversity may be better understood as changes in caregiving allocation strategies rather than a simple gain or loss of maternal care.

neuroscience↗
bioRxiv2026

The Computational Grammar of Human Behaviour in a Biological Environment

Human behaviour unfolds as an extended stream of spontaneous actions shaped by environmental demands and the agent's goals. The organisation of these actions, situated between setting abstract goals and concrete movement execution, remains poorly characterised. Here, we introduce DynaClade, an unsupervised temporal action segmentation algorithm for human full-body motion capture data, and apply it to freely moving participants navigating ecologically realistic risky foraging environments in virtual reality. DynaClade identifies discrete actions whose kinematic characteristics and spatial distributions correspond to environmental affordances, supporting the validity of the approach. Among these actions, we discovered a hitherto undescribed movement pattern defined by increased body sway without locomotion. Action sequences were highly non-random and showed clear history dependence beyond first-order Markov structure, most of which was explained by a second-order prediction. This higher-order structure was well captured in a hidden Markov model, in which some of the observed actions were associated with more than one latent state. Each of these latent states corresponded to the same action in a distinct action context. These findings suggest that spontaneous human actions are predominantly selected based on the current action and context, rather than following pre-planned or habitually assembled sequences.

neuroscience↗