Abstract
Building and functioning of the human brain requires the precise orchestration and execution of myriad molecular and cellular processes, across a multitude of cell types and over an extended period of time. Dysregulation of these processes affects structure and function of the brain and can lead to neurodevelopmental, neurological, or psychiatric disorders. Multiple environmental stimuli affect neural stem cells (NSCs) at several levels, thus impairing the normal human neurodevelopmental program. In this review article, we will delineate the main mechanisms of infection adopted by several neurotropic pathogens, and the selective NSC vulnerability. In particular, TORCH agents, i.e., Toxoplasma gondii, others (including Zika virus and Coxsackie virus), Rubella virus, Cytomegalovirus, and Herpes simplex virus, will be considered for their devastating effects on NSC self-renewal with the consequent neural progenitor depletion, the cellular substrate of microcephaly. Moreover, new evidence suggests that some of these agents may also affect the NSC progeny, producing long-term effects in the neuronal lineage. This is evident in the paradigmatic example of the neurodegeneration occurring in Alzheimer’s disease.
Highlights
The immense complexity of the human brain is reflected in its cellular organization and in the cognitive and behavioral repertoire that defines us as human
Rubella virus (RV) infection of progenitor cells could lead to a variety of malformations of the central nervous system (CNS), like developmental delay and microcephaly that are frequently reported in infants with congenital rubella syndrome (CRS)
Mutations in the genes encoding for amyloid precursor protein (APP), PSEN1, and PSEN2 are responsible for an autosomal dominant form of the disease, which typically strikes less than 1% of the patients [204]
Summary
The immense complexity of the human brain is reflected in its cellular organization and in the cognitive and behavioral repertoire that defines us as human. Intermediate Progenitor Cells (IPCs or Basal Progenitors): Neural progenitors generated from neuroepithelial cells and RGCs at the apical surface of the ventricular zone. Adult Neural Stem Cells: Populations of multipotent neural stem cells mainly present in two specialized niches of the adult mammalian brain, the subventricular or subependymal zone of the lateral ventricle wall and the subgranular zone of the dentate gyrus They maintain neurogenesis and gliogenesis throughout adult life in rodents and other mammals, but their presence and activity in humans is still debated. Austin Smith’s group has described a population of NSCs derived from 5–7 pcw human hindbrain [22] These cells, named hindbrain (hb) neuroepithelial stem (NES) cells, are neurogenic and preserve their original regional identity, exhibiting for the first time a stable wide degree of plasticity. Special emphasis will be given to human NSC model systems employed to unravel mechanisms perturbating human neurodevelopment and/or producing neurodegeneration
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