Laminar distribution of neuropeptide Y-immunoreactive neurons in human prefrontal cortex during development

Abstract

Neuropeptide Y (NPY) is present in neurons of the adult human cerebral cortex. In view of the reported roles of NPY in the central nervous system in health and during certain disease conditions, we have studied normal development of NPY immunoreactivity (-ir) in the human prefrontal cortex (PFC), Brodmann areas 9 and 46. Twenty-six specimens ranging from the ages of 14 postovulatory weeks to 34 years exhibited patterns that revealed six periods in the development of the laminar distribution and density of NPY-ir neurons. Changes during prenatal and perinatal periods reflect the onset, development, and resolution of the transient fetal telencephalic compartments, including the subplate zone, in which NPY-ir neurons are especially abundant. Before the age of 1 year, the majority of NPY-ir neurons were found in the subplate zone, whereas, after 1 year, the majority were seen in the cortical layers. This is in contrast with the human visual cortex, where the majority of NPY-ir neurons were still located in the white matter. The density of cortical NPY-ir neurons increased in the fifth developmental period (ages 4-7 years), coinciding with the increase of cortical volume and marked progression of cognitive functions. The adult pattern of a relatively low density of cortical NPY-ir neurons was reached in period 6 (from about 8 years), when individual variation also became apparent. Our data point to a protracted maturation of NPY-ir in the human PFC and to different distribution patterns of NPY-ir neurons in different cortical areas.

Subplate in the developing cortex of mouse and human

“…The NPY-positive subplate neurons are found superficially near to the cortical plate in human and could form part of the local GABAergic circuitry (Delalle et al 1997;Bayatti et al 2008), whereas KCC2-positive neurons localize to the border with the intermediate zone (Bayatti et al 2008; Fig. 4 of the present study).…”

Interneurons in the developing human neocortex

“…These interneurons become more numerous in humans during the second half of gestation, not studied here. Indeed, Sst + , PV + and NPY + neurons were reported in later stages of gestation in human cerebral cortex (Kostovic et al, 1991; Cao et al, 1996; Yan et al, 1997; Delalle et al, 1997; Bayatti et al, 2007). Similarly, in mice these markers were expressed only after birth (Gonchar et al, 2007).…”

NPY mRNA expression in the prefrontal cortex: Selective reduction in the superficial white matter of subjects with schizoaffective disorder

“…During development of the cerebral cortex, the earliest born cells form the preplate which is subsequently split into the marginal zone (adult layer 1) and the subplate (adult deep layer 6 and superficial white matter) by later born neurons which migrate to become the cortical plate (adult layers 2 - superficial 6) (Kostovic and Rakic 1980). Interestingly, NPY protein is present very early in human development in the preplate neurons underlying DLPFC areas 9 and 46; and in adult human prefrontal cortex, NPY protein is most strongly expressed by neurons located in the residual preplate (layer 1, deep layer 6, and the underlying white matter) (Delalle et al 1997; Uylings and Delalle 1997). Thus, the vulnerable neurons in subjects with schizoaffective disorder, that is those with concurrent psychotic symptoms and a mood disorder, appear to be residual preplate neurons.…”