Diabetes, adult neurogenesis and brain remodeling: New insights from rodent and zebrafish models

Abstract

The prevalence of diabetes rapidly increased during the last decades in association with important changes in lifestyle. Diabetes and hyperglycemia are well-known for inducing deleterious effects on physiologic processes, increasing for instance cardiovascular diseases, nephropathy, retinopathy and foot ulceration. Interestingly, diabetes also impairs brain morphology and functions such as (1) decreased neurogenesis (proliferation, differentiation and cell survival), (2) decreased brain volumes, (3) increased blood-brain barrier leakage, (4) increased cognitive impairments, as well as (5) increased stroke incidence and worse neurologic outcomes following stroke. Importantly, diabetes is positively associated with a higher risk to develop Alzheimer disease. In this context, we aim at reviewing the impact of diabetes on neural stem cell proliferation, newborn cell differentiation and survival in a homeostatic context or following stroke. We also report the effects of hyper- and hypoglycemia on the blood-brain barrier physiology through modifications of tight junctions and transporters. Finally, we discuss the implication of diabetes on cognition and behavior.

Obesity-induced type 2 diabetes impairs neurological recovery after stroke in correlation with decreased neurogenesis and persistent atrophy of parvalbumin-positive interneurons

“…As in striatum, the initial stages of hippocampal neurogenesis after stroke (by quantitating the proliferative marker Ki67 and the neuroblast marker DCX 2 weeks after stroke) were also impaired by obesity/T2D. These results are in line with previous studies [10,29,30,75]. Interestingly, in contrast with striatum, the generation of hippocampal mature neurons 6 weeks after stroke (by detecting double positive BrdU/NeuN mature neurons) was also severely suppressed by obesity/T2D.…”

“…The effect of diabetes on basal adult neurogenesis has been previously described in rodent in vivo (for review, see [75]) and in vitro models [69,76]. Different models as well as differences in the stages of the diabetes development at the time of investigation, resulted in discrepancies ranging from decrease to no effect or even increase in the proliferative activity of NSCs and neural progenitor cells [75].…”

“…The effect of diabetes on basal adult neurogenesis has been previously described in rodent in vivo (for review, see [75]) and in vitro models [69,76]. Different models as well as differences in the stages of the diabetes development at the time of investigation, resulted in discrepancies ranging from decrease to no effect or even increase in the proliferative activity of NSCs and neural progenitor cells [75]. Although the negative effect of toxin-induced hyperglycemia on the initial stages of striatal neurogenesis after stroke has been reported by Zhang et al [10], the effect of obesity-induced T2D on the generation of new, mature neurons in striatum has not been previously determined.…”

Impaired brain homeostasis and neurogenesis in diet-induced overweight zebrafish: a preventive role from A. borbonica extract

“…It fits with another model of high caloric consumption in zebrafish resulting in decreased cerebellar proliferation 59 . In addition, in mammals, genetic and/or diet models of overweight/obesity were shown to result in decreased neural stem cell proliferation and subsequently to a lower number of newborn neurons generated 54,[60][61][62][63] . Such a decreased neurogenesis was also observed in other metabolic disorders including hyperglycemia in both rodents and fish 18,64 .…”

No stress—better results?

“…The practical course was coordinated and managed by a PhD student (ACD) working on the impact of stress and/or hyperglycemia on physiological parameters (3)(4)(5). This combination made for an ideal scenario where under-and postgraduate students could interact and thereby contribute to successful teaching and learning outcomes.…”