Selective destruction of mossy fibers and granule cells with preservation of the GABAergic network in the inferior region of the rat hippocampus after colchicine treatment.

Lesions induced by colchicine injection into the rat hippocampus were investigated by means of electron microscopy and GABA immunocytochemistry. Granule cells were nearly completely destroyed 3 days after colchicine injection; since the necrosis of their axonal endings was delayed, an anterograde degeneration of the mossy fibers had probably taken place. The selectivity of the lesions was not limited to granule cells, for some pyramidal neurons in CA1 pyramidal layer were damaged. It was, however, striking to observe that throughout the hippocampal structure GABAergic neurons were spared from the effects of colchicine. For instance, GABAergic neurons were found in the vicinity of the completely destroyed granule cell layer. GABAergic neurons and terminals were also present in the CA3 region where the GABA-containing terminals formed a dense network of synapses with somata and dendrites of pyramidal cells. It was interesting to note that, consistent with previous studies, the GABAergic neurons in CA3 are innervated by mossy fibers. We conclude that after colchicine treatment the destruction of the granule cells was not associated with a lesion of the GABAergic network. This selective lesion provides a useful model with which to study the properties of CA3 neurons deprived of their major excitatory input but with an intact inhibitory network.

Distribution of GABAergic neurons in late fetal and early postnatal rat hippocampus.

The ontogenesis of GABAergic neurons in the rat hippocampus was studied using an anti-GABA serum. GABA immunoreactivity appeared at the 18th day of gestation. At this stage, GABA-immunoreactive (GABA-IR) cells are grouped in two layers, one located deeply in the intermediate zone near the ventricular zone, and the other found superficially in the marginal zone near the hippocampal fissure. During the late embryonic and early postnatal life, GABA-IR neurons progressively disappeared from these two layers. The transient appearance of an abundant network of GABAergic neurons might be due to transient expression of GABA in some neurons or to cellular death. Later on, from the third postnatal day, the GABA-IR neurons appeared throughout the whole hippocampus according to a dorsoventral and lateromedial gradient. The setting of neuronal bodies preceded that of GABA-IR puncta (supposed to be mainly synaptic boutons) around the neuronal cell bodies and along the dendritic shafts. The puncta are only visible from the sixth day onwards and their number increased rapidly during the first 3 postnatal weeks. Our results indicate that GABA may have a role in neurotransmission in the hippocampus from a very early stage of development.

Development of mossy fiber synapses in hippocampal slice culture.

The mossy fiber synaptogenesis has been studied in hippocampal slice cultures. In vivo mossy fiber terminals contact the thorny excrescences of CA3 pyramidal neurons over a restricted portion, i.e. the proximal part of the apical dendrite. In organotypic cultures mossy fibers expand their terminal field and invade the infrapyramidal area of the CA3 region and the supragranular layer of the dentate gyrus. Newly formed mossy fiber synapses in CA3 region were examined, through electron microscopy, in cultures taken at various time intervals. The main events of the formation of newly formed mossy fiber synapses can be summarized as follows. During the first week following explantation mossy fiber axons contact the dendritic shaft of the pyramidal dendrite and establish both symmetrical and asymmetrical contacts. Subsequent modifications occur in the postsynaptic portion facing the mossy fiber bouton: (i) a massive accumulation of polyribosomes and coated vesicles in the subsynaptic cytoplasm; (ii) undulations of the plasma membrane; (iii) disappearance of neurotubules at postsynaptic sites and appearance of a fine network of filamentous material. Later on in culture, complex giant spines invaginate within the synaptic bouton. In conclusion this study shows that CA3 pyramidal neurons following deafferentation retain the capacity to form thorny excrescences, when contacted by mossy fibers. Moreover these results suggest a crucial role for mossy fibers to induce the formation of thorny excrescences in an heterotopic localization, i.e. over the basilar dendrites of CA3 pyramidal neurons.

[Congenital hereditary motor and sensory neuropathy]. / Neuropathies héréditaires sensitivomotrices à début congénital.

The authors report 6 cases of hereditary sensorimotor neuropathy (HSMN) presenting with the following clinical features: (1) severe outcome (3 out of 6 patients died before the age of 4 years), and (2) intellectual impairment (3 out of 6 cases). Histopathological study of nerve biopsies gave heterogeneous results: there was one case of axonal neuropathy (HSMN II of Dyck and Lambert), one case of demyelinating neuropathy with Schwann's cell proliferation (HSMN III of Dyck and Lambert), and one case of giant axonal neuropathy. The last three cases displayed an original pattern hitherto unknown in classical delayed HSMN, with complete disappearance of myelinated sheaths and Schwann's cell proliferation. This particular pattern did not seem to be due to the biopsy being performed at an early stage, since in one case a second biopsy showed the same histological features.

Iatrogenic Creutzfeldt-Jakob disease in three growth hormone recipients: a neuropathological study.

Since 1985, several cases of Creutzfeldt-Jakob disease, occurring after a treatment by human cadaveric hormone have been reported. Three new iatrogenic cases observed in French patients (two children and one young adult) are described here. Neuropathological study displayed the classical aspects of previously reported sporadic cases of Creutzfeldt-Jakob disease in adults, including severe cortical spongiform change with numerous vacuoles within neuronal dendrites, diffuse astrogliosis and neuronal loss. In addition, the iatrogenic cases described here included two more unusual points: (i) they were homozygotic for the PrP gene on codon 129 and therefore a genetic predisposition could be suspected; (ii) numerous kuru plaques were scattered in the cerebral cortex, the subcortical white matter and in the cerebellar cortex. They were decorated with a PrP monoclonal antibody, but not with a beta A4 antibody. This last point underlines the similarities between iatrogenic Creutzfeldt-Jakob disease and kuru.