Ultrastructural Remodeling of the Neurovascular Unit in the Female Diabetic db/db Model—Part III: Oligodendrocyte and Myelin

Melvin Hayden,Vincent Demarco,Deana Grant,Aranyra Aroor

doi:10.3390/neuroglia1020024

Melvin Hayden, Vincent Demarco + Show 2 more

Open Access

https://doi.org/10.3390/neuroglia1020024

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Abstract

Obesity, insulin resistance, and type 2 diabetes mellitus are associated with diabetic cognopathy. In this study, we tested the hypothesis that neurovascular unit(s) (NVU), oligodendrocytes, and myelin within cerebral cortical grey matter and deeper transitional zone regions between the cortical grey matter and white matter may be abnormal. The monogenic (Leprdb) female diabetic db/db [BKS.CgDock7m +/+ Leprdb/J] (DBC) mouse model was utilized for this ultrastructural study. Upon sacrifice (20 weeks of age), left-brain hemispheres of the DBC and age-matched non-diabetic wild type control C57BL/KsJ (CKC) mice were immediately immersion-fixed. We found prominent remodeling of oligodendrocytes with increased nuclear chromatin condensation and volume and increased numbers of active myelination sites of the cytoplasm in transition zones. Marked dysmyelination with outer myelin lamellae sheath splitting, separation, and ballooning with aberrant mitochondria in grey matter and similar myelin remodeling changes with marked disarray with additional axonal collapse in transitional zones in DBC as compared to CKC models.

Highlights

Myelin is a multilayered lamellar sheath that enwraps axons in the grey and white matter in the brain and is synthesized in the brain by the oligodendroglia
Michalski and Kothary [1] have set forth a paradigm for development of mature OLs in four distinct phases: (i) the birth, migration and proliferation of oligodendrocyte precursor cells (OPC), that occurs in waves; followed by (ii) morphological differentiation with the OL establishing an expansive synthetic network of OL cytoplasmic processes; followed by (iii) axonal contact, which leads to myelin wrapping—Neueronglsiah2e01a8t, h1,mx FeOnRtPEoEfRtRaErVgIEeWted neuronal axons with ensuing generation of extr2emof e14ly electron dense and compact myelin with an enduring (iv) long-term trophic and metabolic support system for maintenanccyetoapnladsmpicropteroccteisosnes;offomlloyweelidnabtyed(iini)euaxroonnasl [c1o]n.tact, which leads to myelin wrapping—
Myelination in layer III cortical grey matter. These panels depict the marked difference between the myelinatiomnyeinlinlaatiyoenroIfIaIxcoonrstiincathlegcroeryticmal agrteteyrm

Summary

Introduction

Myelin is a multilayered lamellar sheath that enwraps axons in the grey and white matter in the brain and is synthesized in the brain by the oligodendroglia. If myelin undergoes any significant abnormal remodeling change there may be a delay in the in the arrival of information to the more distant regional neurons with subsequent cognitive impairment [6,7].

Results

Conclusion