Objectives: The aim of this morphometric study was to determine whether the developmental trajectories of neurons within the dorsal, ventral and lateral parts of the substania nigra, the source of dopaminergic innervation of the human striatum, are similar to the pattern of development of four striatal subdivisions including the caudate, putamen, nucleus accumbens and globus pallidus.
Methods: We applied the Nucleator method to detect patterns of developmental changes of neuronal soma and nuclear volume within five subdivisions of the nigro-striatal system in the brains of 12 subjects with idiopathic autism and 12 age-matched controls.
Results: Volume of neurons within the three subdivisions of the substantia nigra, including the dorsal, ventral and lateral parts innervating four parts of the striatum was almost identical in the autistic and control subjects both 4 to 8 years of age and >8 years of age.
However, in the brains of autistic children 4 to 8 years of age we found a significant delay of neuron growth with the volume of cell body smaller than in control subjects by 22% in the caudate nucleus (0.025*), by 21% in the putamen (p<0.042*), by 31% in the globus pallidus (p<0.008**) and by 37% in the nucleus accumbens (p<0.004**). The volume of neuron nucleus was also significantly reduced. No significant difference between the volume of neuronal soma and nucleus in autistic and control subjects >8 years of age suggests that a correction of neuronal growth occurs in late childhood and adulthood.
Conclusions:
The observed pattern indicates a normal development of neurons producing dopamine but a delayed development of striatal neurons. It suggests that development of the nigro-striatal system is desynchronized and that the repetitive and stereotyped behaviors in autism are driven by delayed development of neurons within the striatum but not in the substantia nigra.