Biology subjects

Backman, L.

Publications and source records attributed to Backman, L..

3 recordsLinked to original sources

bioRxiv2024

Mechanical loading modulates AMPK and mTOR signaling in myblasts

Skeletal muscle adaptation to exercise involves various phenotypic changes that enhance metabolic and contractile functions. One key regulator of these adaptive responses is the activation of AMPK, influenced by exercise intensity. However, the mechanistic understanding of AMPK activation during exercise remains incomplete. In this study, we utilized an in vitro model to investigate the effects of mechanical loading on AMPK activation and its interplay with the mTOR signaling pathway. Proteomic analysis of myoblasts subjected to static loading (SL) revealed distinct quantitative protein alterations associated with RNA metabolism, with 10% SL inducing the most pronounced response compared to lower intensity of 5% and 2% as well as control. Additionally, 10% SL suppressed RNA and protein synthesis, while activating AMPK and inhibiting the mTOR pathway. Our RNA sequencing analysis further corroborated these findings, revealing numerous differentially regulated genes and signaling pathways influenced by both AMPK and mTOR. Further examination showed that SL induced changes in mitochondrial biogenesis and the ADP/ATP ratio. These findings provide novel insights into the cellular responses to mechanical loading and shed light on the intricate AMPK-mTOR regulatory network in myoblasts.

biophysics↗

bioRxiv2023

Dopamine D1-receptor Organization Contributes to Functional Brain Architecture

Decades of research on functional brain mapping have highlighted the importance of understanding the functional organization of the cerebral cortex. Recent advances have revealed a gradient of functional organization spanning from primary sensory to transmodal cortices. This gradient-like axis of connectivity has been hypothesized to be aligned with regional differences in the density of neuromodulatory receptors. Recent work in non-human primates supports this notion, revealing a gradient of dopamine D1-like receptor (D1DR) density along the cortical hierarchy. Given the importance of dopaminergic modulation for synaptic activity and neural gain, we tested whether D1DRs shares the same organizational principles as brain function in humans, and whether inter-regional relationships in D1 expression modulate functional crosstalk. Using the worlds largest combined dopamine D1DR-PET and MRI database, we provided empirical support for the first time in humans that the landscape of D1DR availability follows a unimodal-transmodal cortical hierarchy, with greater D1DR expression in associative cortical regions. We found an organization of inter-regional D1DR co-expression spanning unimodal to transmodal brain regions, expressing a high spatial correspondence to the principal macroscale gradient of functional connectivity. Critically, we found that individual differences in D1DR density between unimodal and transmodal regions was associated with greater differentiation of default-mode and somatosensory networks. Finally, inter-regional D1DR co-expression was found to modulate couplings within, but not between, functional networks. Together, our results show that D1DR co-expression provides a biomolecular layer to the functional organization of the brain. Significance StatementWe found a high correspondence between the organization of the most abundantly expressed dopamine receptor subtype and a macroscale unimodal-to-transmodal functional gradient. Differences in D1 density between unimodal and transmodal regions were related to the shape of the functional gradient, contributing to greater differentiation of somatomotor and default mode networks. Finally, we observed that the covariance structure of dopamine D1 receptors is associated with the strength of connectivity within functional networks. The discovery of a dopaminergic layer of brain organization represents a crucial first step towards an understanding of how dopamine, with close ties to behavior and neuropsychiatric conditions, potentially contribute to the emergence of functional brain organization.

neuroscience↗

bioRxiv2023

Two long-axis dimensions of hippocampal cortical integration support memory function across the adult lifespan

The hippocampus is a complex structure critically involved in numerous behavior-regulating systems. In young adults, multiple overlapping spatial modes along its longitudinal and transverse axes describe the organization of its functional integration with neocortex, extending the traditional framework emphasizing functional differences between sharply segregated hippocampal subregions. Yet, it remains unknown whether these modes (i.e., gradients) persist across the adult human lifespan, and relate to memory and molecular markers associated with brain function and cognition. In two independent samples, we demonstrate that the principal anteroposterior and second-order, mid-to-anterior/posterior hippocampal modes of neocortical functional connectivity, representing distinct dimensions of macroscale cortical organization, manifest across the adult lifespan. Specifically, individual differences in topography of the second-order gradient predicted episodic memory and mirrored dopamine D1 receptor distribution, capturing shared functional and molecular organization. Older age was associated with less distinct transitions along gradients (i.e., increased functional homogeneity). Importantly, a youth-like gradient profile predicted preserved episodic memory - emphasizing age-related gradient dedifferentiation as a marker of cognitive decline. Our results underscore a critical role of mapping multidimensional hippocampal organization in understanding the neural circuits that support memory across the adult lifespan.

neuroscience↗