Neuroglia in cognitive reserve

Abstract

The concept of cognitive reserve was born to account for the disjunction between the objective extent of brain damage in pathology and its clinical and intellectual outcome. The cognitive reserve comprises structural (brain reserve) and functional (brain maintenance, resilience, compensation) aspects of the nervous tissue reflecting exposome-driven life-long plasticity, which defines the ability of the brain to withstand aging and pathology. The mechanistic background of this concept was primarily focused on adaptive changes in neurones and neuronal networks. We present arguments favoring the more inclusive view, positing that neuroglia are fundamental for defining the cognitive reserve through homeostatic, neuroprotective, and neurodegenerative mechanisms. Neuroglia are critical for the life-long shaping of synaptically connected neuronal circuits as well as the brain connectome thus defining cognitive reserve. Neuroglial homeostatic and protective physiological responses define brain maintenance and resilience, while neuroglia regenerative capabilities are critical for brain compensation in pathology. Targeting neuroglia may represent an untrodden path for prolonging cognitive longevity.

Fig. 1. Neuroglia contribution to the cognitive reserve.

Neuroglial cells are fundamental for all aspects of cognitive reserve. Brain reserve. Neuroglia working in concert with neurones define the brain structure and shapes its cytoarchitecture. Radial glia (prenatally) and stem radial astrocytes (postnatally) provide for neurogenesis. Astrocytes, through secretion of multiple factors such as trombospondins, hevins, glypicans, and cholesterol stimulate synaptogenesis, control synaptic maturation, and provide material for the adaptive remodelling of neuronal membranes. Microglia thorough synaptic pruning and trogocytosis shape synaptically connected neuronal ensembles, while oligodendroglial cells support connectome and provide for activity-dependent life-long myelination. Brain maintenance and brain resilience. Neuroglial cells through multiple molecular cascades support CNS homeostasis and define brain resilience through numerous protective pathways. Brain compensation. Neuroglia are central element of brain defense and regeneration; reactive glial cells erect perilesional barriers, remove pathogens and cellular debris, and orchestrate regeneration.