Human fetal hippocampal development: I. Cytoarchitecture, myeloarchitecture, and neuronal morphologic features

Abstract

To characterize better the process of anatomic development of the human hippocampus, we studied the cytoarchitecture, myeloarchitecture, and neuronal morphology in human fetal and postnatal hippocampi. Twenty cases were studied in which the ages ranged from 9 weeks gestation through 62 years. Fixed, paraffin-embedded, hippocampal sections were stained with cresyl violet for Nissl substance and immunolabeled for myelin basic protein. The hippocampal region at 9 weeks contains 4 layers: a ventricular zone, an intermediate zone, a homogeneous-appearing hippocampal plate comprised of bipolar-shaped neurons, and a wide marginal zone. At 15-19 weeks, individual subfields can be distinguished. A distal-to-proximal gradient of cytoarchitectural and neuronal morphologic maturity is seen, with the subiculum appearing more developed than the ammonic subfields and the dentate gyrus appearing least mature. Within each subfield, an "inside-out" gradient of maturity is also evident. By 32-34 weeks gestational age, neurons in CA2 and CA3 have undergone rapid enlargement and morphologic maturation, surpassing CA1, which still contains some immature neurons. The dentate gyrus is the latest area to develop, only assuming a mature cytoarchitecture after 34 weeks. The essential cytoarchitectural appearance of the hippocampal subfields is stable after birth, although there is progressive neuronal enlargement and a decrease in neuronal density throughout childhood into adulthood. Myelination is first evident near term, with strong myelin basic protein immunoreactivity present in the angular bundle, alveus, and fimbria and relatively scant immunoreactivity in the nascent perforant pathway. Myelination in the hippocampus increases in childhood until adolescence, after which the pattern remains unchanged. These studies delineate normal neuroanatomic development and can be used to understand better the mechanisms underlying human neurodevelopmental and neurodegenerative disorders of the hippocampal formation.

Perinatal Iron Deficiency Predisposes the Developing Rat Hippocampus to Greater Injury from Mild to Moderate Hypoxia—Ischemia

“…Altered myelin production and maintenance associated with iron deficiency (Beard et al, 2003) also may have been responsible for the enhanced demyelination. Whether perinatal HI injury results in demyelination in the human hippocampus, where myelinated fibers are first seen at 39 weeks but peak myelination occurs after birth (Arnold and Trojanowski, 1996), is not known. Table 1.…”

Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium

“…The convergence of data from these findings in the CA2 subfield is interesting, since CA2/CA3 neurons are an important information processing point between the dentate gyrus and the subiculum. 13 However the CA2 subfield does not appear to have a developmental trajectory separate from that of other hippocampal subfields, 14 and does not appear to have an unusual degree of vulnerability to degenerative processes or hypoxia. 15 Indeed, other commentators have made the case that molecular findings in the CA4-CA3 subfields, 4 and in the subiculum 16 may have more direct relevance for mental disorders.…”

Translating developmental time across mammalian species

“…A crown to rump length is often used to`age' a human fetus, but this measurement can be confusing between studies (Humphrey, 1968;Rakic and Yakovlev, 1968) and variable even within studies (Rakic and Yakovlev, 1968). The`delay' factor is likely to be unusually large for human observations, as intervals between ages used in an individual developmental study may be relatively large (Hewitt, 1961;Zilles et al, 1986;Mojsilovic and Zecevic, 1991;Arnold and Trojanowski, 1996).…”