Inverse association of Pin1 and tau accumulation in Alzheimer's disease hippocampus

Neurofibrillary degeneration, one of the pathological hallmarks of Alzheimer's disease, is not ubiquitous to all brain regions or neurons. While a high degree of vulnerability has been documented for entorhinal cortex, hippocampal and neocortical pyramidal neurons other brain structures are largely spared. Even within highly vulnerable regions such as hippocampus neurons are affected to a variable extent. The molecular basis for this selective susceptibility remains unknown. Neurofibrillary degeneration involves hyperphosphorylation of tau which critically impairs its binding capacity to microtubule and, therefore, is believed to disrupt the axonal cytoskeleton. Recently, Lu et al. [Nature (1999) 399:784] described the ability of the peptidyl-prolyl cis-trans isomerase Pin1 to recover microtubule-binding affinity and microtubule stabilisation of phosphorylated tau. In the present study, we analysed the potential involvement of Pin1 in selective vulnerability of hippocampal neurons to neurofibrillary degeneration in Alzheimer's disease. Pin1 immunoreactivity appeared as cytoplasmic granules affecting hippocampal subfields to a different extent (CA2>subiculum>CA1>CA3/CA4). Since the main markers of granulovacuolar degeneration do not co-label Pin1-immunoreactive granules, we propose that these granules may represent a new lesion in Alzheimer's disease. Neurons containing Pin1 granules were devoid of neurofibrillary tangles. Granular accumulation of Pin1 may correspond to an absence of neurofibrillary lesions in these cells and might be associated with other mechanisms of neuronal degeneration.     

Effects of lesions of the caudal cerebellar vermis on cardiovascular regulation in awake cats

The vestibular system is known to participate in cardiovascular regulation during movement and postural alterations. The present study considered whether lesions of two regions of the posterior cerebellar vermis (the nodulus and uvula) that provide inputs to vestibular nucleus regions that affect control of blood pressure would alter cardiovascular responses during changes in posture. Blood pressure and heart rate were monitored in awake cats during nose-up tilts up to 60 degrees in amplitude before and following aspiration lesions of the nodulus or uvula; in most animals, cardiovascular responses were also recorded following the subsequent removal of vestibular inputs. Lesions of the nodulus or uvula did not affect baseline blood pressure or heart rate, although cardiovascular responses during nose-up tilts were altered. Increases in heart rate that typically occurred during 60 degrees nose-up tilt were attenuated in all three animals with lesions affecting both dorsal and ventral portions of the uvula; in contrast, the heart rate responses were augmented in the two animals with lesions mainly confined to the nodulus. Furthermore, following subsequent removal of vestibular inputs, uvulectomized animals, but not those with nodulus lesions, experienced more severe orthostatic hypotension than has previously been reported in cerebellum-intact animals with bilateral labyrinthectomies. These data suggest that the cerebellar nodulus and uvula modulate vestibulo-cardiovascular responses, although the two regions play different roles in cardiovascular regulation.     

Dysregulation of neuronal differentiation and cell cycle control in Alzheimer's disease

Degeneration in Alzheimer's disease primarily occurs in those neurons that in the adult brain retain, a high degree of structural plasticity and, is associated with the activation of mitogenic signaling and cell cycle activation. Brain areas affected by neurofibrillary degeneration in Alzheimer's disease are structures involved in the regulation of "higher brain functions" that become increasingly predominant as the evolutionary process of encephalization progresses. The functions these areas subserve require a life-long adaptive reorganization of neuronal connectivity. With the increasing need during evolution to organize brain structures of increasing complexity, these processes of dynamic stabilization and de-stabilization become more and more important but might also provide the basis for an increasing rate of failure. The hypothesis is put forward that it is the labile state of differentiation of a subset of neurons in the adult brain that allows for ongoing morphoregulatory processes after development is completed but at the same time renders these neurons particularly vulnerable. Interferring with neuronal differentiation control might, thus, be a potential strategy to prevent neurodegeneration in Alzheimer's disease and related disorders.     

Health in a 24-h society

With increasing economic and social demands, we are rapidly evolving into a 24-h society. In any urban economy, about 20% of the population are required to work outside the regular 0800-1700 h working day and this figure is likely to increase. Although the increase in shiftwork has led to greater flexibility in work schedules, the ability to provide goods and services throughout the day and night, and possibly greater employment opportunities, the negative effects of shiftwork and chronic sleep loss on health and productivity are now being appreciated. For example, sleepiness surpasses alcohol and drugs as the greatest identifiable and preventable cause of accidents in all modes of transport. Industrial accidents associated with night work are common, perhaps the most famous being Chernobyl, Three Mile Island, and Bhopal.     

Thromboendangiitis obliterans des Gehirns im Kindesalter

Zusammenfassung Auf Grund einer erst durch die Sektion festgestellten Thromboendangiitis obliterans bei einem 8 jährigen Kinde wird auf die differential-diagnostischen Schwierigkeiten in der Abgrenzung gegen andere gefäßbedingte, entzündliche und raumfordernde Prozesse hingewiesen. Ein klinisches Syndrom läßt sich bei diesem Krankheitsbild nicht aufstellen, wenn auch die Zweiteilung von Lindenberg u. Spatz wichtige Hinweise für die Diagnosestellung geben kann. Auch bei Jugendlichen ist die Diagnose einer funktionellen Gefäßstörung nur mit Vorsicht zu stellen.Die morphologische Untersuchung der Gefäßveränderungen bei der Thromboendangiitis obliterans besonders mit Trichromfärbungen weist auf eine Störung in der Schrankenfunktion des Endothels hin. Diese geweblichen Umgestaltungen in dem System Blutflüssigkeit-Endothel-Parenchym fassen wir mit Bredt als Entzündung auf. Der durch W. W. Meyer auf Grund von Kombinationsfärbeverfahren aufgestellte Begriff der fibrinösen interstitiellen Entzündung kann bei der Thromboendangiitis obliterans am Gehirn durch die Färbung nach Cleveland-Wolfe bestätigt werden.     

Trends in neuropathology (author's transl)

Neuropathology has been originated in clinical necessity and trended progressively towards independence in the last 30 years all over the world. In the future, substance and methods in neuropathology demand a good correlation to clinical and theoretical branches of medicine and a solid integration in the manner to work and to think in modern morphology.