Cell Number and Neuropil Alterations in Subregions of the Anterior Hippocampus in a Female Monkey Model of Depression

Background: The anterior hippocampus is associated with emotional functioning and hippocampal volume is reduced in depression. More women are clinically depressed than men, yet the depressed female brain is little studied. We reported reduced anterior hippocampal volume in behaviorally depressed adult female cynomolgus macaques; the mechanisms contributing to that reduction are unknown. The present study represents the first systematic morphological investigation of the entire hippocampus in depressed female primates. Methods: Cellular determinants of hippocampal size were examined in subregions of anterior and posterior hippocampus in antidepressant-naive, adult female monkeys characterized for behavioral depression and matched on variables that influence hippocampal size (n = 8 depressed, 8 nondepressed). Unbiased stereology was used to estimate neuronal and glial numbers, neuronal soma size, and regional and layer volumes. Results: Neuropil and cell layer volumes were reduced in cornu ammonis (CA) 1 and dentate gyrus (DG) of the anterior but not the posterior hippocampus of depressed compared with nondepressed monkeys. Glial numbers were 30% lower in anterior CA1 and DG of depressed monkeys, with no differences observed in the posterior hippocampus. Granule neuron number tended toward a reduction in anterior DG; pyramidal neuron number was unchanged in any region. Size of pyramidal neurons and glial densities tended to be reduced throughout the whole hippocampus of depressed monkeys, whereas neuronal densities were unchanged. Conclusions: The reduced size of the anterior hippocampus in depressed female monkeys appears to arise from alterations in numbers of glia and extent of neuropil, but not numbers of neurons, in CA1 and DG.