Biology subjects

Maretich, P.

Publications and source records attributed to Maretich, P..

4 recordsLinked to original sources

bioRxiv2026

Adrenal remodeling encodes stress axis memory to shape fentanyl seeking

The hypothalamic-pituitary-adrenal (HPA) axis is implicated in substance use disorders, yet the features of this circuit that contribute to addiction vulnerability remain unclear. Here, we show that fentanyl engages with different components of the HPA axis, and this engagement varies across timescales. Within minutes, fentanyl activated corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVNCRH) and transiently increased adrenocorticotropic hormone (ACTH) levels. Hours to days later, fentanyl suppressed PVN activity, reduced adrenal size, and impaired corticosterone release. Conversely, ACTH-induced adrenal hypertrophy, increased corticosterone, suppressed fentanyl-evoked PVNCRH activity, and elevated fentanyl-seeking behavior. These findings identify adrenal remodeling as a physiological record of stress history that shapes neuroendocrine and behavioral responses to fentanyl, mechanistically linking stress and addiction while revealing treatment targets for opioid dependence.

neuroscience↗

bioRxiv2024

Fiber-based Probes for Electrophysiology, Photometry, Optical and Electrical Stimulation, Drug Delivery, and Fast-Scan Cyclic Voltammetry In Vivo

Recording and modulation of neuronal activity enables the study of brain function in health and disease. While translational neuroscience relies on electrical recording and modulation techniques, mechanistic studies in rodent models leverage genetic precision of optical methods, such as optogenetics and imaging of fluorescent indicators. In addition to electrical signal transduction, neurons produce and receive diverse chemical signals which motivate tools to probe and modulate neurochemistry. Although the past decade has delivered a wealth of technologies for electrophysiology, optogenetics, chemical sensing, and optical recording, combining these modalities within a single platform remains challenging. This work leverages materials selection and convergence fiber drawing to permit neural recording, electrical stimulation, optogenetics, fiber photometry, drug and gene delivery, and voltammetric recording of neurotransmitters within individual fibers. Composed of polymers and non-magnetic carbon-based conductors, these fibers are compatible with magnetic resonance imaging, enabling concurrent stimulation and whole-brain monitoring. Their utility is demonstrated in studies of the mesolimbic reward pathway by simultaneously interfacing with the ventral tegmental area and nucleus accumbens in mice and characterizing the neurophysiological effects of a stimulant drug. This study highlights the potential of these fibers to probe electrical, optical, and chemical signaling across multiple brain regions in both mechanistic and translational studies.

neuroscience↗

bioRxiv2023

HiExM: high-throughput expansion microscopy enables scalable super-resolution imaging

Expansion microscopy (ExM) enables nanoscale imaging using a standard confocal microscope through the physical, isotropic expansion of fixed immunolabeled specimens. ExM is widely employed to image proteins, nucleic acids, and lipid membranes in single cells; however, current methods limit the number of samples that can be processed simultaneously. We developed High-throughput Expansion Microscopy (HiExM), a robust platform that enables expansion microscopy of cells cultured in a standard 96-well plate. Our method enables [~]4.2x expansion of cells within individual wells, across multiple wells, and between plates. We also demonstrate that HiExM can be combined with high-throughput confocal imaging platforms to greatly improve the ease and scalability of image acquisition. As an example, we analyzed the effects of doxorubicin, a known cardiotoxic agent, on human cardiomyocytes (CMs) as measured by Hoechst signal across the nucleus. We show a dose dependent effect on nuclear DNA that is not observed in unexpanded CMs, suggesting that HiExM improves the detection of cellular phenotypes in response to drug treatment. Our method broadens the application of ExM as a tool for scalable super-resolution imaging in biological research applications. Significance StatementExpansion microscopy (ExM) is an accessible and widely used technique for super-resolution imaging of fixed biological specimens. For many ExM users, slide-based sample preparation and manual imaging limit the number of experimental conditions and samples that can be processed in parallel. Here, we develop a simple and inexpensive device that enables ExM within the wells of a standard 96-well cell culture plate. We show that samples prepared with our workflow can be imaged with a high-throughput autonomous confocal microscope, allowing for scalable super-resolution image acquisition, greatly increasing data output. Our device retains the accessibility of ExM while extending its application to research questions that require the analysis of many conditions, treatments, and time points.

bioengineering↗

bioRxiv2020

Cell size is a determinant of stem cell potential during aging

Stem cells are remarkably small in size. Whether small size is important for stem cell function is unknown. We find that murine hematopoietic stem cells (HSCs) enlarge under conditions known to decrease stem cell function. This decreased fitness of large HSCs is due to reduced proliferative potential. Preventing HSC enlargement by inhibiting macromolecule biosynthesis or reducing large HSCs size by shortening G1 averts the loss of stem cell potential under conditions causing stem cell exhaustion. Finally, we show that a fraction of murine and human HSCs enlarge during aging. Preventing this age-dependent enlargement improves HSC function. We conclude that small cell size is important for stem cell function in vivo and propose that stem cell enlargement contributes to their functional decline during aging. One Sentence SummarySize increase drives stem cell aging.

cell biology↗