Developmentally Regulated Expression of HDNF/NT-3 mRNA in Rat Spinal Cord Motoneurons and Expression of BDNF mRNA in Embryonic Dorsal Root Ganglion

Northern blot analysis was used to demonstrate high levels of hippocampus-derived neurotrophic factor/neurotrophin-3 (HDNF/NT-3) mRNA in the embryonic day (E) 13 - 14 and 15 - 16 spinal cord. The level decreased at E18 - 19 and remained the same until postnatal day (P) 1, after which it decreased further to a level below the detection limit in the adult. In situ hybridization revealed that the NT-3 mRNA detected in the developing spinal cord was derived from motoneurons and the decrease seen at E18 - 19 was caused by a reduction in the number of motoneurons expressing NT-3 mRNA. The distribution of NT-3 mRNA-expressing cells in the E15 spinal cord was very similar to the distribution of cells expressing choline acetyltransferase or nerve growth factor receptor (NGFR) mRNA. Moreover, a striking similarity between the developmentally regulated expression of NT-3 and NGFR mRNA was noted in spinal cord motoneurons. A subpopulation of all neurons in the dorsal root ganglia expressed brain-derived neurotrophic factor (BDNF) mRNA from E13, the earliest time examined, to adulthood. These results are consistent with a trophic role of NT-3 for proprioceptive sensory neurons innervating the ventral horn, and imply a local action of BDNF for developing sensory neurons within the dorsal root ganglia.     

Membranous lipodystrophy

Summary The case is described of a 35-year-old housewife diagnosed as having membranous lipodystrophy (as described by Nasu et al. in 1970 and called lipomembranous polycystic osteodysplasia by Hakola in 1972). The main symptom of this patient was a slowly progressive dementia. Skeletal symptoms were not seen. The computerized tomogram of the brain showed calcification of bilateral basal ganglia and the plain roentgenograms of the bones revealed cystic radiolucent areas at the distal end of the bones of the patient's extremities. Histological examination of the curetted material from the right talus revealed a membranocystic pattern. The fatty tissue curetted from the cyst of the talus and the lysosomal enzymes of the white blood cells were biochemically normal. A possible relationship between this disease entity and connective disorders is considered.     

Alteration of basal ganglia evoked responses by reserpine and L-Dopa

The effects of reserpine and L-Dopa on basal ganglia evoked potentials were investigated in cats. The caudate response resulting from substantia nigra stimulation and the substantia nigra response elicited by globus pallidus stimulation were increased at several hours after the systemic administration of reserpine. L-Dopa in the presence of dopa decarboxylase inhibition (MK-486) depressed these responses and reversed the effect of reserpine at 0.5 h after administration. Reserpine did not reverse the L-Dopa effect. Reserpine and L-Dopa caused no significant change in responses between other basal ganglia structures. These data give evidence that the basal ganglia are major sites for reserpine and L-Dopa action.     

Evolution of changes in neuronal activity in the subthalamic nucleus of rats with unilateral lesion of the substantia nigra assessed by metabolic and electrophysiological measurements

Cellular expression of cytochrome oxidase subunit I (COI) mRNA has recently been used as a metabolic marker for neuronal activity to study the functional changes in the subthalamic nucleus (STN) in parkinsonism. The previous experimental studies have been performed when the pathological state was stabilized at a maximal level. In order to determine the evolution of changes in neuronal activity in the STN after nigrostriatal denervation, we analysed by in situ hybridization the cellular expression of COI mRNA in the subthalamic neurons at different times, from 6 h to 14 days, after unilateral intranigral microinjection of 6-hydroxydopamine (6-OHDA) in rats. In parallel, the time-dependent changes of the unit neuronal activity of subthalamic neurons have been recorded. Levels of COI mRNA increased by 41% in subthalamic neurons from 24 h after 6-OHDA intoxication, to 14 days (+26%). Similarly, electrical activity started to increase slightly 24 h after lesion (+20%) and remained significantly higher at 14 days after the lesion (+189%). Changes in neuronal mean discharge rate were associated with changes in the pattern of spiking activity, from a regular firing pattern to an irregular one with a high bursting activity. These results show that: (i) the hyperactivity of the STN represents a very early phenomenon in the physiopathology of parkinsonian syndromes; and (ii) that changes in COI mRNA expression slightly precede changes in electrical neuronal activity.     

Combined lesions of cholinergic and serotonergic neurons in the rat brain using 192 IgG-saporin and 5,7-dihydroxytryptamine: neurochemical and behavioural characterization

This study assessed behavioural and neurochemical effects of i.c.v. injections of both the cholinergic toxin 192 IgG-saporin (2 microgram) and the serotonergic toxin 5,7-dihydroxytryptamine (5,7-DHT; 150 microgram) in Long-Evans female rats. Dependent behavioural variables were locomotor activity, forced T-maze alternation, beam walking, Morris water-maze (working and reference memory) and radial-maze performances. After killing by microwave irradiation, the concentrations of acetylcholine, monoamines and 5-hydroxyindoleacetic acid (5-HIAA) were measured in the hippocampus, frontoparietal cortex and striatum. 192 IgG-saporin reduced the concentration of acetylcholine by approximately 40% in the frontoparietal cortex and hippocampus, but had no effect in the striatum. 5,7-DHT lesions reduced the concentration of serotonin by 60% in the frontoparietal cortex and 80% in the hippocampus and striatum. Noradrenaline was unchanged in all structures except the ventral hippocampus where it was slightly increased in rats given 192 IgG-saporin. Cholinergic lesions induced severe motor deficits but had no other effect. Serotonergic lesions produced diurnal and nocturnal hyperactivity but had no other effect. Rats with combined lesions were more active than those with only serotonergic lesions, showed motor dysfunctions similar to those found in rats with cholinergic lesions alone, and exhibited impaired performances in the T-maze alternation test, the water-maze working memory test and the radial-maze. Taken together and although cholinergic lesions were not maximal, these data show that 192 IgG-saporin and 5,7-DHT lesions can be combined to selectively damage cholinergic and serotonergic neurons, and confirm that cholinergic-serotonergic interactions play an important role in some aspects of memory, particularly in spatial working memory.     

MRI in tick-borne encephalitis

The tick-borne encephalitis (TBE) virus gives rise to epidemic encephalitis. Mild forms usually manifest as influenza-like episodes or are clinically silent. MRI is usually normal in TBE. We describe severe TBE in a patient who presented with fever and altered mental status after a tick bite and a specific antibody response to TBE. MRI revealed pronounced signal abnormalities in the basal ganglia and thalamus, without contrast enhancement. These findings coincide well with neuropathological studies of severe nerve cell degeneration with inflammatory cell infiltrates, neuronophagia and reactive astrocytosis in the deep grey matter. We review the literature and discuss the relevant differential diagnosis. Received: 10 November 1999/Accepted: 4 February 2000     

Sperm number and condition affect the number of basal cells and their expression of macrophage antigen in the murine epididymis

Unilateral ligation of the mid-corpus epididymis, the proximal vas deferens and imposition of an abdominal temperature for 6 days as well as bilateral castration for 3, 6 or 14 days, resulted in a change in epithelial composition of the adult murine epididymis with regard to the number and antigen expression of basal cells. There were fewer basal cells per tubule cross-section with fewer expressing F4/80 antigen when spermatozoa were absent from the proximal lumen following short-term castration. Conversely, more basal cells with more of them demonstrating macrophage antigen expression were evident when more or damaged spermatozoa were in the proximal lumen after corpus ligation and exposure to abdominal temperature or in the cauda after long-term withdrawal of androgen support. By contrast, ligation of the vas deferens did not lead to tubule distension, and hence sperm accumulation, and did not alter the basal cell population in the cauda epididymis. The data suggest that epididymal basal cells respond in number and macrophage antigen expression to the presence of sperm autoantigens in the lumen with little dependence on circulating androgens. These changes may represent responses to minimise the interaction of sperm autoantigens with the immune system and the risk of immunological infertility.     

Two children with xeroderma pigmentosum developing two different types of malignancies simultaneously

Patients with xeroderma pigmentosum (XP) are highly sensitive to ultraviolet radiation and prone to develop multiple skin malignancies. We report two children under 6 years of age with XP who each developed two histologically different types of malignancies simultaneously. We conclude that it is of importance to be aware of the possibility of multiple malignancies of different types, even in young children. Accepted: 16 December 1996     

Dexamethasone induces TrkA and p75NTR immunoreactivity in the cerebral cortex and hippocampus

Nerve growth factor (NGF) plays a crucial role in synaptic plasticity during brain development and adulthood by activating a dual receptor system composed of TrkA and p75 (p75NTR) receptors. Exogenous NGF modulates the expression of both receptors. Little is known about the ability of endogenous NGF to regulate the expression of these receptors in basal forebrain cholinergic terminals. The ability of glucocorticoids to increase NGF expression in the hippocampus prompted us to investigate whether the synthetic glucocorticoid dexamethasone (DEX) increases TrkA and p75NTR expression in NGF-target cholinergic neurons in developing rats. We first examined the effect of DEX on NGF mRNA by in situ hybridization. DEX given systemically (0.5 mg/kg, sc) for 1 week to 7-day-old rats elicited an increase in NGF mRNA levels in the dentate gyrus of the hippocampus and superficial layers II and III of the cerebral cortex. Immunohistochemical analysis of p75NTR and TrkA levels revealed a dramatic increase in p75NTR immunoreactivity (IR) in both basal forebrain and hippocampus and TrkA IR in the hippocampus. Interestingly, in DEX-treated rats more axonal terminals were immunopositive for p75NTR in the hippocampus and cortex, suggesting an increase in p75NTR IR in cell bodies as well as in terminals. Our data indicate that the endogenously produced NGF elicits biological changes similar to those of the exogenously delivered NGF. We suggest that glucocorticoids might regulate and coordinate cholinergic neuronal maturation by increasing the biosynthesis of NGF.