Dataset Information

Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner.

ABSTRACT: In multiple neurodevelopmental and neurodegenerative disorders, endosomal changes correlate with changes in exosomes. We examined this linkage in the brain of mice that received cocaine injections for two weeks starting at 2.5 months of age. Cocaine caused a decrease in the number of both neuronal early and late endosomes and exosomes in the brains of male but not female mice. The response to cocaine in ovariectomized females mirrored male, demonstrating that these sex-differences in response to cocaine are driven by hormonal differences. Moreover, cocaine increased the amount of α-synuclein per exosome in the brain of females but did not affect exosomal α-synuclein content in the brain of males, a sex-difference eliminated by ovariectomy. Enhanced packaging of α-synuclein into female brain exosomes with the potential for propagation of pathology throughout the brain suggests a mechanism for the different response of females to chronic cocaine exposure as compared to males.

SUBMITTER: Barreto BR

PROVIDER: S-EPMC9352616 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Publications

Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner.

Barreto Bryana R BR D'Acunzo Pasquale P Ungania Jonathan M JM Das Sasmita S Hashim Audrey A Goulbourne Chris N CN Canals-Baker Stefanie S Saito Mitsuo M Saito Mariko M Sershen Henry H Levy Efrat E

Neurochemical research 20220430 8

In multiple neurodevelopmental and neurodegenerative disorders, endosomal changes correlate with changes in exosomes. We examined this linkage in the brain of mice that received cocaine injections for two weeks starting at 2.5 months of age. Cocaine caused a decrease in the number of both neuronal early and late endosomes and exosomes in the brains of male but not female mice. The response to cocaine in ovariectomized females mirrored male, demonstrating that these sex-differences in response to ...[more]

PMID: 35501523

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Project description:Lymph nodes are highly specialized immune organs that orchestrate the adaptive immune response. In the lymph nodes, naïve B and T lymphocytes encounter cognate antigens, sparking their activation and response to foreign substances. Lymph nodes grow in response to an immune challenge, at least in part to accommodate increased numbers of infiltrating and proliferating B and T lymphocytes. This behavior is supported by a robust three-dimensional network of extracellular matrix (ECM) fibers and fibroblastic reticular cells (FRCs). ECM fibers and FRCs work synergistically to alternate stretching and contractile forces between them allowing the lymph node to maintain structural integrity during rapid tissue reconstruction. These changes ultimately alter the material properties of the lymph node, which can impact cell migration, proliferation, and differentiation. Recent work has investigated the physiological implications of the changing lymph node microenvironment; however, the biophysical properties of the lymph nodes during these changes remain largely unexplored. Here, we use multiple particle tracking microrheology (MPT), a minimally invasive nanoparticle-based technique to investigate the biophysical properties (elastic/loss moduli, microviscosity, pore size) of lymph nodes post inflammatory stimulus. Our results highlight mechanical changes both during the initial phases of the acute inflammatory response and upon resolution of inflammation, a topic that is relatively understudied. We show that B and T cell rich areas restructure independently, with T cell zones remodeling significantly and exhibiting nearly a 3-fold higher elastic modulus. Additionally, for the first time, we show that biological sex modulates lymph node biomechanics in acute inflammation: Lymph nodes from female mice showed a ~20-fold increase in elastic and loss moduli at peak inflammation, while lymph nodes from male mice had a ~5-fold decrease in both moduli. Additionally, lymph nodes from female mice appeared to permanently remodel during the resolution of acute inflammation resulting in the maintenance of an overall higher elastic and loss modulus, while lymph nodes from male mice returned to the biomechanics of untreated lymph nodes. We also found that at least some of the changes in biomechanical properties were correlated with changes in ECM materials in the lymph nodes, suggesting a structure-function relationship. Overall, our studies provide key insights into how biomechanical properties in lymph nodes are altered during inflammation, a previously unstudied area, and lay the foundation for structure-function relationships involved in immune response. Additionally, we demonstrate a robust technique for the analysis of the lymph node interstitial tissue properties and how they vary with inflammatory stimuli.

Dataset Information

Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner.

Publications

Cocaine Modulates the Neuronal Endosomal System and Extracellular Vesicles in a Sex-Dependent Manner.

Similar Datasets

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