Biology subjects

Sugimura, Y.

Publications and source records attributed to Sugimura, Y..

3 recordsLinked to original sources

bioRxiv2021

Transcriptomes of Electrophysiologically Recorded Dbx1-derived Inspiratory Neurons of the preBötzinger Complex in Neonatal Mice

Breathing depends on interneurons in the preBotzinger complex (preBotC) derived from Dbx1-expressing precursors. Here we investigate whether rhythm- and pattern-generating functions reside in discrete classes of Dbx1 preBotC neurons. In a slice model of breathing with [~]5 s cycle period, putatively rhythmogenic Type-1 Dbx1 preBotC neurons activate 100-300 ms prior to Type-2 neurons, putatively specialized for output pattern, and 300-500 ms prior to the inspiratory motor output. We sequenced Type-1 and Type-2 transcriptomes and identified differential expression of 123 genes including ionotropic receptors (Gria3 and Gabra1) that may explain their preinspiratory activation profiles and Ca2+ signaling (Cracr2a, Sgk1) involved in inspiratory and sigh bursts. Surprisingly, neuropeptide receptors that influence breathing (e.g., {micro}-opioid and bombesin-like peptide receptors) were only sparsely expressed, which suggests that cognate peptides and opioid drugs exert their profound effects on a small fraction of the preBotC core. These data in the public domain help explain breathings neural origins.

neuroscience↗

bioRxiv2021

Systematic analysis of brain lactate and pH levels in 65 animal models related to neuropsychiatric conditions

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2,294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimers disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

neuroscience↗

bioRxiv2020

Cross-ecosystem transcriptomics identifies distinct genetic modules for nutrient acquisition in maize

Plants have evolved diverse strategies for the acquisition of the macro-nutrients phosphorus and nitrogen; e.g., mycorrhizal formation, root development, and secretion of chelators/hydrolases to liberate inorganic phosphate. Despite the extensive studies on the individual strategies, there is little information about how plants regulate these strategies in response to fluctuating environment. We approached this issue via profiling transcriptomes of plants grown in large environmental gradients. Roots, leaves, and root-zone soils of 251 maize plants were collected across the US Corn Belt and Japan. RNA was extracted from the roots and sequenced, and the leaves and soils were analyzed. Nineteen genetic modules were defined by weighted gene coexpression network analysis and functionally characterized according to gene ontology analysis, by which we found three modules that are directly involved in nutrient acquisition: mycorrhizal formation, phosphate-starvation response (PSR), and root development. Correlation analysis with soil and plant factors revealed that both phosphorus and nitrogen deficiencies upregulated the mycorrhizal module, whereas the PSR module was upregulated mainly by deficiency in phosphorus relative to nitrogen. Expression levels of the root development module were negatively correlated with those of the mycorrhizal module, suggesting that nutrient acquisition through the two pathways, mycorrhizas and roots, are opposite strategies that are employed under nutrient-deficient and -enriched conditions, respectively. The identification of the soil and plant factors that drive the modules has implications for sustainable agriculture; activation/optimization of the strategies is feasible via manipulating the factors. Overall, our study opens a new window for understanding plant response to complex environments.

plant biology↗