Immunocytochemical investigations on the presence of neuron-specific antibodies in the CSF of Parkinson's disease cases

The CSF and sera of 7 patients with Parkinson's disease were investigated immunocytochemically, in order to see if antibodies were present which recognized DA-ergic cell bodies in glutaraldehyde fixed rat brain. In 2 patients a marked labeling of DA-ergic neurons in the substantia nigra was observed, identified by anti-DA antiserum and by 6-OHDA induced degeneration, but also other neurons in the ventral mesencephalon were recognized. The other patients were weakly positive or negative. Sera gave unspecific labelling of all neurons. In one patient the sub-classes of IgG were investigated and found to be of IgG₃ (labeling nerve terminals) and of IgG_1–2, low affinity type (recognizing perikarya). The epitopes recognized have not been identified, but are unlikely to be DA-like, since blocking experiments and ELISA-tests gave negative results. The possible clinical importance of the results are discussed.Special Issue dedicated to Prof. Holger Hydén.     

Attraction of the sexes inFormica lugubris Zett (Hymenoptera: Formicidae)

Summary Sexuals ofFormica lugubris fly to mating places, where females attract males by using a sex pheromone. Females collected on the nest surface before departing on a mating flight are much less attractive than those collected on the mating place after the mating flight, suggesting that the mating flight triggers the release of the sex pheromone. Olfactory cues are essential for males to locate females while they patrol. Males probably use visual cues to locate females once they have alighted nearby them. Males are also attracted by aggregations of other males on the ground, probably because one or several females are likely to be close to male aggregations.     

Enzymes Related to Monoamine Transmitter Metabolism in Brain Microvessels

The activities of tyrosine hydroxylase, aromatic L-aminoacid decarboxylase, monoamine oxidase, and catechol-O-methyltransferase were measured in microvessel (capillaries and venules), parenchymal arterioles, and pial vessels from rat brains, and the decarboxylase activity was compared in brain microvessels from rabbit, cat, dog, pig, cow, baboon, and man. Cranial sympathectomy was performed to estimate the neuronal contribution to the enzyme activities. All vascular regions had substantial activities of the various enzymes studied. The activity of aromatic L-aminoacid decarboxylase in cerebral microvessels was high in rat, dog, pig, cow, and man; intermediate in rabbit and cat; and low in baboon. In addition to this enzyme, cerebral microvessels also contained tyrosine hydroxylase and monoamine oxidase. Aromatic aminoacid decarboxylase and monoamine oxidase serve an enzymatic barrier function at the microvascular level, whereas the main function of tyrosine hydroxylase is probably to synthesize monoamines within nerve terminals that remain in close association with microvessels under the conditions used for preparation of the microvascular fraction. In larger intracerebral and pial vessels monoamine oxidase was present both in the wall itself and in perivascular sympathetic nerves; the remaining two enzymes had a primarily neuronal localization. The latter types of vessels also contained catechol-O-methyltransferase in their walls.     

Recovery of brain noradrenaline after 5,7-dihydroxytryptamine-induced axonal lesions in the rat

Time-dependent changes in regional CNS noradrenaline (NA) concentration, 3H-NA uptake and fluorescence morphology of CNS NA neurons were analysed in the adult rat up to 6 months after intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT), and compared with the time-course of changes in brain and spinal cord indolamine neurons. Following a substantial depletion of both amines in all CNS regions (telodiencephalon, brainstem and spinal cord) at 10 days after 150 mug 5,7-DHT, brain NA--but not 5-HT--levels recovered to near-normal values in brainstem and forebrain (35% below the age-matched controls) within 4 months. This was accompanied by a total restoration of the initially decreased capacity of the brain tissue to accumulate 3H-NA in vitro. Within 10 days after 5,7-DHT, there was a disappearance of NA terminals from many telencephalic, diencephalic and lower brain stem nuclei, from the cerebral and cerebellar cortices, and the grey matter of the spinal cord, concomitant with the appearance of numerous distorted, highly fluorescent swellings along the non-terminal axons of the major noradrenergic projection pathways. The recovery of the NA levels was paralleled by a re-appearance of fluorescent fibres, signifying an intense sprouting and regrowth of the drug-lesioned axons, which eventually re-innervated some of the previously denervated telodiencephalic regions. Except for a permanent loss of some surface-near perikarya in group A1 (the main source of the bulbospinal projections) there was no evidence of a retrograde degeneration of noradrenergic cell bodies in the rat CNS. The results are compatible with the idea that 5,7-DHT mainly causes a lesion of NA axons at a distance from the cell bodies, and this is followed by sprouting and regrowth of axons from the lisioned neurites, and formation of new terminal-like fibres in some previously denervated telodiencephalic regions. These findings indicate that chemical axotomy of central NA neurons induced by 5,7-DHT is--in contrast to that induced by 6-hydroxydopamine--followed by extensive axonal regeneration.     

Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy

Cancer incidences are growing and cause millions of deaths worldwide. Cancer therapy is one of the most important challenges in medicine. Improving therapeutic outcomes from cancer therapy is necessary for increasing patients’ survival and quality of life. Adjuvant therapy using various types of antibodies or immunomodulatory agents has suggested modulating tumor response. Resistance to apoptosis is the main reason for radioresistance and chemoresistance of most of the cancers, and also one of the pivotal targets for improving cancer therapy is the modulation of apoptosis signaling pathways. Apoptosis can be induced by intrinsic or extrinsic pathways via stimulation of several targets, such as membrane receptors of tumor necrosis factor-α and transforming growth factor-β, and also mitochondria. Curcumin is a naturally derived agent that induces apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing reactive oxygen species (ROS) production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of NF-κB and COX-2, which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis PI3K signaling and increase the expression of MAPKs to induce endogenous production of ROS. In this paper, we aimed to review the molecular mechanisms of curcumin-induced apoptosis in cancer cells. This action of curcumin could be applicable for use as an adjuvant in combination with other modalities of cancer therapy including radiotherapy and chemotherapy.