Sensory neuron cultures derived from adult db/db mice as a simplified model to study type-2 diabetes-associated axonal regeneration defects

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dc.contributor.authorDe Gregorio, Cristian
dc.contributor.authorEzquer, Fernando
dc.date.accessioned2022-03-10T15:14:39Z
dc.date.available2022-03-10T15:14:39Z
dc.date.issued2021
dc.description.abstractDiabetic neuropathy (DN) is an early common complication of diabetes mellitus (DM), leading to chronic pain, sensory loss and muscle atrophy. Owing to its multifactorial etiology, neuron in vitro cultures have been proposed as simplified systems for DN studies. However, the most used models currently available do not recreate the chronic and systemic damage suffered by peripheral neurons of type-2 DM (T2DM) individuals. Here, we cultured neurons derived from dorsal root ganglia from 6-month-old diabetic db/db-mice, and evaluated their morphology by the Sholl method as an easy-to-analyze readout of neuronal function. We showed that neurons obtained from diabetic mice exhibited neuritic regeneration defects in basal culture conditions, compared to neurons from non-diabetic mice. Next, we evaluated the morphological response to common neuritogenic factors, including nerve growth factor NGF and Laminin-1 (also called Laminin-111). Neurons derived from diabetic mice exhibited reduced regenerative responses to these factors compared to neurons from non-diabetic mice. Finally, we analyzed the neuronal response to a putative DN therapy based on the secretome of mesenchymal stem cells (MSC). Neurons from diabetic mice treated with the MSC secretome displayed a significant improvement in neuritic regeneration, but still reduced when compared to neurons derived from non-diabetic mice. This in vitro model recapitulates many alterations observed in sensory neurons of T2DM individuals, suggesting the possibility of studying neuronal functions without the need of adding additional toxic factors to culture plates. This model may be useful for evaluating intrinsic neuronal responses in a cell-autonomous manner, and as a throughput screening for the pre-evaluation of new therapies for DN.es
dc.description.versionVersión publicadaes
dc.identifier.citationDe Gregorio C, Ezquer F. Sensory neuron cultures derived from adult db/db mice as a simplified model to study type-2 diabetes-associated axonal regeneration defects. Dis Model Mech. 2021 Jan 1;14(1):dmm046334. doi: 10.1242/dmm.046334es
dc.identifier.urihttps://doi.org/10.1242/dmm.046334es
dc.identifier.urihttp://hdl.handle.net/11447/5690
dc.language.isoenes
dc.subjectAdipocytes / cytologyes
dc.subjectAdipose Tissue / cytologyes
dc.subjectAginges
dc.subjectAnimalses
dc.subjectAxons / pathologyes
dc.subjectDiabetes Mellitus, Type 2 / geneticses
dc.subjectDorsal root gangliaes
dc.subjectNeuritic regeneratioes
dc.subjectAdult sensory neuron cultureses
dc.titleSensory neuron cultures derived from adult db/db mice as a simplified model to study type-2 diabetes-associated axonal regeneration defectses
dc.typeArticlees
dcterms.sourceDisease models & mechanismses

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