[Stress-related risk factors for depression in young girls]. / Stressbezogene Einflussfaktoren bei depressiven Mädchen.

The prevalence of major depression in adolescents is remarkable. Stress has been hypothesised to contribute to the maintenance of depression in young patients. This study aims to elucidate stress-related predictive variables for the maintenance of depression in young girls. A longitudinal design with a time interval of six months was used to assess stress load and depression in 135 15-year-old girls. Stress was measured by the "Fragebogen zur Erhebung von Stress und Stressbewältigung im Kindes- und Jugendalter" and the cortisol awakening response as a biological indicator for hyperactivity of the HPA axis. Depression was quantified by the "Depressionsinventar für Kinder und Jugendliche". The data were analysed by multiple linear regression. When adjusting for initial depression, psychological stress load, physical stress symptoms, and stress vulnerability proved to be predictive for depression, whereas chronic stress neither at the psychological level nor as indicated by the cortisol awakening response had statistically significant effects. The results show the stability of depression in adolescent girls, but also prove an additional influence of acute stress variables.

A case of rapidly progressive Rosai-Dorfman disease restricted to the central nervous system.

Sinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman disease (RDD), is an idiopathic condition typically associated with cervical lymphadenopathy, fever and hypergammaglobulinaemia. Extranodal involvement has been reported in diverse sites such as the skin, upper respiratory tract, orbit and the central nervous system. We document a case of intracranial RDD in a 40-year-old woman with rapid evolution over a period of three months. Clinically, the patient suffered from headache. The MRT showed a left parietal tumour with dural attachment. Histologically, the lesion consisted of pale-staining histiocytes with emperipolesis, neutrophilic granulocytes and scattered lymphocytes. Focally, the granulocytes dominated the histological picture. By immunohistochemical analysis, the characteristic histiocytes were positive for S100 protein, CD68 and FXIIIa, but negative for CD1a. No Birbeck-granula were detectable in electron microscopic analysis. Granulocytes showed a positive Anti-HHV6b immunoreaction. The tumour was diagnosed asA'an intracranial manifestation of RDD primary to the CNS with an unusual preponderance of neutrophilic granulocytes and with only scattered lymphocytes. The postoperative clinical staging showed no other manifestations of the disease. On postoperative MRI the lesion had been completely resected. No further therapy has been applied and the patient has had an unremarkable clinical course for the last ten months.

Cortical cholinergic decline parallels the progression of Borna virus encephalitis.

Borna disease virus (BDV)-induced meningoencephalitis is associated with the dysfunction of the cholinergic system. Temporal development of this cholinergic decline during pre-encephalitic and encephalitic stages of BDV infection remains however elusive. Changes in choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities were therefore determined in the cerebral cortex, hippocampus, striatum, amygdala and cholinergic basal forebrain nuclei (ChBFN) of rats infected with BDV. Immunocytochemistry for ChAT and vesicular acetylcholine transporter (VAChT) was employed to identify morphological consequences of BDV infection on cholinergic neurons. Whereas both ChAT and AChE activities changed only slightly under pre-encephalitic conditions, the encephalitic stage was characterized by a significant decrease of ChAT activity in the cerebral cortex, horizontal diagonal band of Broca (hDBB), hippocampus and amygdala concomitant with a marked reduction of AChE activity in the cerebral cortex, hDBB and hippocampus. The striatum and medial septum remained unaffected. ChAT and VAChT immunocytochemistry revealed prominent axonal degeneration in affected cortical and limbic projection areas of ChBFN. In summary, our data indicate progressive deterioration of forebrain cholinergic systems that parallels the progression of BDV encephalitis.

Disturbance of the cortical cholinergic innervation in Borna disease prior to encephalitis.

Rats experimentally infected with the highly neurotropic Borna disease virus (BDV) display a wide variety of dysfunction such as learning deficiencies and behavioral abnormalities. Prior to the onset of encephalitis alterations of one of the major cortical neurotransmitters, acetylcholine, were monitored immunohistochemically by light and electron microscopy of its synthesizing enzyme choline acetyltransferase (ChAT). We found a progressing decrease in the number of ChAT-positive fibers, starting with discrete changes at day 6 post infection (p.i.) and ending with a nearly complete loss of cholinergic fibers, especially in the hippocampus and neocortex, suggesting a massive disturbance of the cholinergic innervation by day 15 p.i.. The fiber pathways (e.g., fimbria-fornix) connecting the basal forebrain with these target areas in the cortex displayed axon spheroids which are often linked to axonal transport dysfunction. No evidence for significant cellular destruction was seen in the brain, including the cells of origin of these axons in the basal forebrain. We conclude that the motor, mood, learning and memory disabilities in BDV-infected rats are likely to result, in part, from cortical cholinergic denervation. The present study gives new insights into the pathogenesis of neurological disease caused by a noncytopathogenic virus.

Analysis of p53 mutation and epidermal growth factor receptor amplification in recurrent gliomas with malignant progression.

Genomic alterations and expression of the p53 tumor suppressor gene and the epidermal factor receptor gene (EGFR) were investigated in 22 patients with primary World Health Organization (WHO) grade II gliomas that on recurrence had progressed to malignant gliomas of WHO grades III or IV. Mutations of the p53 gene (exons 5 to 8) were found in 12 of 22 primary tumors (10 of 13 astrocytomas, 1 of 7 oligodendrogliomas, 1 of 2 oligoastrocytomas). In each of these cases identical p53 mutations were present in the respective malignant recurrences. In all instances in which the p53 mutation was associated with p53 protein accumulation (10 of 12 cases) the percentage of p53 immunopositive tumor cells had increased from the primary to the recurrent tumor. None of the primary low-grade and none of the recurrent high-grade tumors (7 anaplastic astrocytomas, 10 anaplastic oligodendrogliomas, 4 anaplastic oligoastrocytomas, and 5 glioblastomas) showed evidence of EGFR gene amplification. Our results thus demonstrate p53 is mutated in a high fraction of low-grade astrocytomas with progression to anaplastic astrocytomas and glioblastomas and that progression in such cases is frequently associated with an increase in the fraction of p53 immunopositive tumor cells. The general absence of EGFR amplification in our tumor series supports the hypothesis that the significance of p53 mutation and EGFR amplification may be different in glioblastomas that developed by progression from low-grade astrocytomas (secondary glioblastomas) compared to glioblastomas that developed rapidly in a de novo manner without a history of previous low-grade tumor (primary glioblastomas).

Amyloid deposits of immunohistochemically different classes in the ligamentum flavum in biopsies from patients with herniated discs or lumbar spinal stenosis.

Ligamenta flava of 100 patients (n = 107 tissue blocks) were examined for the presence of amyloid by means of polarization microscopy after staining with Congo red. Ninety-three ligamenta flava were resected due to operation of herniated discs while 14 ligamenta flava were obtained after surgical treatment of lumbar spinal stenosis. Amyloid of various amounts (score I-III) and 4 morphologically different appearances were detected in the ligamenta flava of 12 patients. In 6 patients small amyloid deposits were seen along elastic fibres (pattern 1) and/or minute, comma-like deposits in certain areas (pattern 2). In 5 other patients amyloid deposits in form of large lumps were present (pattern 3) intermingled with deposits of pattern 1 and/or 2. Only 1 patient could be detected with amyloid deposits partly associated with blood vessels (pattern 4). The amyloid-containing tissue samples (n = 13) were immunohistochemically analyzed using anti-AA-, anti-A lambda-, anti-A kappa-, anti-ATTR- and anti-A beta 2m-antibodies which are able to identify the major known amyloid classes of tissue sections. Tissues with pattern 1 and 2 amyloid deposits did not react above background with any of the antibodies. In contrast, the 5 patients with pattern 3 amyloid stained strongly with anti-ATTR but not with the other antisera. In this group, therefore, senile systemic amyloid (sporadic ATTR) was also identified which had not been detected at this site before. Consistent with this finding is the advanced age of these patients which was seen to be significantly higher than the average age of the entire group of patients examined.

Physiologically-linked structural plasticity of inhibitory and excitatory synaptic inputs to oxytocin neurons.

The adult oxytocinergic system undergoes extensive synaptic and neuronal-glial remodelling in response to differing conditions of secretion and has become a remarkable example of activity-dependent structural plasticity in the adult mammalian brain. Under stimulation (parturition, lactation, chronic dehydration), glial coverage of oxytocin neurons is significantly reduced and their surfaces become extensively juxtaposed; concurrently, they are contacted by an increased number of synapses. These changes are reversible with cessation of stimulation. We here present observations showing that putative inhibitory and excitatory afferents contribute to this synaptic plasticity. The data are derived from several different comparative analyses of ultrathin sections of the rat supraoptic nucleus (SON) in which presynaptic (gamma-amino butyric acid (GABA) or glutamate) and postsynaptic (oxytocin or vasopressin) partners were identified with postembedding immunogold staining. We thus found that in virgin rats, under basal conditions of oxytocin release, 30-40% of synapses on oxytocinergic or vasopressinergic somata in the SON are GABAergic and about 20% glutamatergic. On the other hand, in lactating rats, in which oxytocin secretion is greatly enhanced, there was an increase in the incidence of both types of synapses, and in particular, on those impinging on oxytocinergic somata.

Synaptic plasticity in the rat supraoptic nucleus during lactation involves GABA innervation and oxytocin neurons: a quantitative immunocytochemical analysis.

The hypothalamic supraoptic nucleus (SON) is known to undergo synaptic remodeling in response to physiological stimuli, such as lactation. We here investigated the involvement of the GABAergic innervation in such plasticity by carrying out comparative ultrastructural analyses after postembedding immunogold labeling for GABA on sections of the SON from virgin and lactating rats. Using random single-section analysis to estimate the numerical density of synapses (from areal measurements of the anterior, mid, and posterior portions of the nucleus), we found that the overall density in either group was about 35 x 10(6) synapses/mm3, of which over one-third were GABA immunoreactive. The GABAergic terminals formed mainly symmetrical synaptic contact on neurosecretory somata and dendrites; the density of axodendritic contacts was twice that of axosomatic contacts. Despite hypertrophy of the neurosecretory neurons in lactating rats, the overall synaptic density did not diminish and was similar to that evaluated in virgin rats. When we estimated synaptic densities in the neuropil (by subtracting the proportion of sampled areas occupied by soma profiles), we found a statistically significant increase in the density of GABAergic synapses, in particular in the mid and posterior portions of the SON in lactating animals. On the other hand, the density of GABA-immunonegative synapses did not differ in the two groups. Terminals contacting more than one postsynaptic element in the same plane of section ("shared" synapses) were visible in the nuclei of virgin and lactating rats and about half in each group were GABAergic. They were comparatively rare but their incidence doubled in lactating animals.(ABSTRACT TRUNCATED AT 250 WORDS)