Hippocampus, concepts

NGF also has actions within the CNS, although it is not particularly abundant in the CNS. Its synthesis appears to be largely restricted to the hippocampus and neocortex, and even in these regions it is present at relatively low concentrations relative to the other neurotrophins. The most prominent population of NGF-responsive neurons expressing TrkA are the basal forebrain cholinergic neurons. The principal projections of these neurons are to the hippocampus and cortex, which conforms with the concept that NGF acts as a target-derived trophic factor in the CNS, just as it does in the peripheral nervous system (PNS). NGF also acts on a subpopulation of cholinergic neurons within the striatum. These interneurons express the NGF receptor, TrkA, and respond to NGF. However, they do not appear to rely entirely on NGF for their survival, and the specific actions of NGF on this neuronal population have not been clearly defined. NGF may also have autocrine actions in the CNS, as some neuronal populations have been identified that express both TrkA and NGF. 

Morphometric magnetic resonance imaging (MRI) studies provide further support for the concept of a subtle developmental brain anomaly. Szeszko et al. (1999) noted that OCD patients had reduced orbito-frontal and amygdala volumes bilaterally, and absence of the normal hemispheric asymmetry of the hippocampus-amygdala complex. Morphometric measurements of the basal ganglia also reveal decreased caudate size (Robinson et al., 1995 Jenike et al., 1996). 

A conspicuous feature of hypoglycemic brain damage in the rat is neuronal necrosis in the dentate gyrus (Fig. 3.4) of the hippocampus (Auer et al., 1985). This seems to be due to the proximity of the NMDA receptors of the molecular layer of the dentate, to the CSF spaces containing the excitatory amino acid aspartate. A similar picture of dentate necrosis is seen sometimes, in human cases of hypoglycemic coma. Although the concept of excitotoxicity was unknown in 1938, toxicity of some kind was postulated by Arthur Weil, when he noticed dentate gyrus neurons near the CSF were necrotic in rabbits (Weil et al., 1938). 

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