Developmental neuroplasticity and the origin of neurodegenerative diseases

Abstract

Several lines of evidence support a link between developmental neuroplasticity and neurodegenerative processes later in life. A deeper insight into these processes is necessary to design strategies to mitigate or even prevent neurodegenerative pathologies.

Expression of neurodegenerative disease‐related proteins and caspase‐3 in glioneuronal tumours

“…In conclusion, our data provides evidence of ongoing cell injury and vulnerability to neuronal degeneration in GNT, similar to other developmental lesions associated with overactivation of the mTOR pathway. This study, together with functional evidence in experimental models [70,76,87], supports the potential link between neurodevelopmental and neurodegenerative pathways. For the interpretation of these observational data we should also consider that proteins (representing hallmarks of neurodegenerative diseases) have distinct physiological functions in both developing and adult human brain and a their deregulation could also reflect a recapitulation of a developmental programme contributing to pathological neuroplasticity (for review see [71]).…”

“…Accordingly, epileptiform discharges and spontaneous recurrent seizures have been reported in a mouse models of AD [65] and it has been known for some time that seizures occur in some patients with tauopathies [66], supporting the role of dysfunctional tau in intractable epilepsy [67]. Moreover, as a high level of phosphorylation of the tau protein is observed during foetal development [68,69], an abnormal phosphorylation of tau may reflect the immature properties of the neuronal component of the tumour or even a recapitulation of a developmental programme contributing to pathological neuroplasticity [69–71].…”

In utero and lactational exposure to low-doses of the pyrethroid insecticide cypermethrin leads to neurodevelopmental defects in male mice—An ethological and transcriptomic study

“…By showing that in utero and lactational exposure to the pyrethroid insecticide cypermethrin induces abnormal brain development during early life, long-lasting behavioral defects during adulthood and gene expression changes related to mitochondrial functioning, DNA regulation and protein metabolism, the present study strongly substantiates the DOHAD hypothesis supported by many authors including [ 83 , 84 ]. In line with this, data collected in the present study raises fundamental question on developmental neurotoxicity safety assessment procedures in guidelines emitted by the US EPA and the OECD.…”

The physiological phosphorylation of tau is critically changed in fetal brains of individuals with Down syndrome

“…According to this “developmental hypothesis”, some disorders with tau pathologies might reflect a recapitulation of a developmental phosphorylation programme . Interestingly, the phosphorylation at Ser‐202/Thr‐205, a reliable marker of all tau pathologies in the adult brain, seems to play a pivotal role in normal brain development and is absent in DS brains.…”