Box 3 | Dendrite abnormalities in human diseases

From the following article:

Branching out: mechanisms of dendritic arborization

Yuh-Nung Jan & Lily Yeh Jan

Nature Reviews Neuroscience 11, 316-328 (May 2010)

doi:10.1038/nrn2836

Human cortical neurons start growing dendrites soon after they have entered their destined cortical layer155. With the arrival of thalamic or cortical afferent fibres and the expression of NMDA (N-methyl-D-aspartate) receptors, pyramidal neurons undergo a second phase of dendrite branching and extension until the third postnatal month156. Whereas layer V pyramidal neurons in the prefrontal cortex reach peak dendrite complexity between the third and sixteenth postnatal months, layer IIIC pyramidal neurons seem dormant during this period, and resume dendrite growth over the next 14 months156. The number of synapses and spines also approaches a maximum in early childhood, followed by synaptic pruning in adolescence10. Intriguingly, intellectual ability seems to correlate with an accelerated and prolonged increase of cortical thickness in childhood followed by equally vigorous cortical thinning in adolescence157. As discussed below, dendrite development shows strong temporal correlation with the emergence of behavioural symptoms of several mental disorders.

Mental disorders such as autism3, 4, 5and Rett's syndrome7 are often associated with abnormal brain size, suggesting overgrowth or lack of dendrite pruning as well as alterations of neuronal number during development. The emergence of behavioural symptoms in the first 3 years of life further begs the question whether abnormal dendrite morphogenesis contributes to these neurodevelopmental disorders. Single gene mutations linked to diseases such as Rett's syndrome, Angelman's syndrome, tuberous sclerosis and fragile X syndrome are known to greatly increase the risk for autism. However, the genetic underpinning of autism remains elusive in most cases despite the high heritability4, 10, 53, 158.

In contrast to mental disorders with early manifestation of macrocephaly and behavioural symptoms, which may arise from overgrowth or lack of dendrite pruning in early childhood, schizophrenia could arise from over-pruning or failed maintenance of dendrites later in life. Notably, recent MRI studies reveal progressive grey-matter loss before and during psychosis development in schizophrenia in late adolescence, suggesting synaptic over-pruning9, 159. Despite the heritability of schizophrenia160 and associated progressive brain volume changes161, and the linkage of schizophrenia to mutations of neuregulin 1 and its receptor159, 162, the genetic basis for schizophrenia remains largely unknown163.