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

Journal
Disease Models & Mechanisms
ISSN
1754-8403
1754-8411
Date Issued
2021
Author(s)
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85101378734
WoS ID
WOS:000624345100003
DOI
URL
URL Institutional Repository
Abstract
<jats:title>ABSTRACT</jats:title>
<jats:p>Diabetic 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.</jats:p>
Cite this document
De Gregorio, C., & Ezquer, F. (2021). Sensory neuron cultures derived from adult db/db mice as a simplified model to study type-2 diabetes-associated axonal regeneration defects. Disease Models & Mechanisms, 14(1), dmm046334. https://doi.org/10.1242/dmm.046334
Project(s)
Subjects
type-2 diabetes mellitus

; 

diabetic neuropathy

; 

adult sensor y neuron cultures

; 

neuritic regeneration

; 

dorsal root ganglia

; 

adipocytes

; 

adipose tissue

; 

aging

; 

animals

; 

axons

; 

blood glucose

; 

cells, cultured

; 

diabetes mellitus, type 2

; 

disease models, animal

; 

disease progression

; 

female

; 

ganglia, spinal

; 

humans

; 

mice

; 

mice, transgenic

; 

nerve growth factors

; 

nerve regeneration

; 

neurites

; 

neurons

; 

secretome

; 

sensory receptor cells

; 

laminin 1

; 

nerve growth factor

; 

neurotrophin

; 

axon

; 

nerve growth factor

; 

adult

; 

animal cell

; 

animal experiment

; 

animal model

; 

article

; 

controlled study

; 

experimental therapy

; 

female

; 

in vitro study

; 

mesenchymal stem cell

; 

mouse

; 

nerve cell

; 

nerve cell culture

; 

nerve fiber regeneration

; 

neurite

; 

neurite outgrowth

; 

non insulin dependent diabetes mellitus

; 

nonhuman

; 

priority journal

; 

sensory nerve cell

; 

spinal ganglion

; 

adipocyte

; 

adipose tissue

; 

aging

; 

animal

; 

cell culture

; 

cytology

; 

disease exacerbation

; 

disease model

; 

genetics

; 

glucose blood level

; 

human

; 

metabolism

; 

nerve regeneration

; 

non insulin dependent diabetes mellitus

; 

pathology

; 

pathophysiology

; 

physiology

; 

sensory nerve cell

; 

spinal ganglion

; 

transgenic mouse