Structure–function relationships in the developing cerebellum: Evidence from early-life cerebellar injury and neurodevelopmental disorders

Abstract

SUMMARY The increasing appreciation of the role of the cerebellum in motor and non-motor functions is crucial to understanding the outcomes of acquired cerebellar injury and developmental lesions in high-risk fetal and neonatal populations, children with cerebellar damage (e.g. posterior fossa tumors), and neurodevelopmental disorders (e.g. autism). We review available data regarding the relationship between the topography of cerebellar injury or abnormality and functional outcomes. We report emerging structure–function relationships with specific symptoms: cerebellar regions that interconnect with sensorimotor cortices are associated with motor impairments when damaged; disruption to posterolateral cerebellar regions that form circuits with association cortices impact long-term cognitive outcomes; and midline posterior vermal damage is associated with behavioral dysregulation and an autism-like phenotype. We also explore the impact of age and the potential role for critical periods on cerebellar structure and child function. These findings suggest that the cerebellum plays a critical role in motor, cognitive, and social–behavioral development, possibly via modulatory effects on the developing cerebral cortex.

Autism genes are selectively targeted by environmental pollutants including pesticides, heavy metals, bisphenol A, phthalates and many others in food, cosmetics or household products

“…A recent MRI study has commented on the co-existence of Chiari malformation with some paediatric autism patients [267]. The targeting of the cerebellum by tretinoin is particularly relevant given that cerebellar abnormalities are a consistent feature of autism [268][269][270]. The transfer of retinoic acid across pig skin is increased by exposure to particulate matter containing polycyclic aromatic hydrocarbons [271].…”

The Cerebellar-Cerebral Microstructure Is Disrupted at Multiple Sites in Very Preterm Infants with Cerebellar Haemorrhage

“…Therefore, cerebellar injury occurring during this vulnerable period is not confined to the cerebellum itself, but may also derail remote supratentorial brain regions from their expected growth trajectory and interfere with crucial cerebellar-cerebral connectivity processes [6,7]. There is now increasing appreciation for the importance of the contributions of the cerebellum to normal motor, cognitive, and behavioural development [8,9]. This knowledge has triggered a reconsideration process of the anatomical and microstructural correlates of adverse outcomes in preterm populations.…”

Structural Basis for the Influence of A1, 5A, and W51W57 Mutations on the Conductivity of the Geobacter sulfurreducens Pili

“…An understanding of the atomic resolution structure and assembly of the G. sulfurreducens pilus provides important insights into their biological functions, including the mechanism of extracellular electron transfer [54]. Point mutations (A1, 5A, and W51W57) of pilA affected the structural details of G. sulfurreducens pilus, i.e., diameter, axial rise, rotation angle, and subunits per turn.…”