Transcriptome Profile Changes in Mice with MPTP-Induced Early Stages of Parkinson's Disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Despite progress in the study of the molecular, genetic, and pathogenic mechanisms of PD, it is unclear which processes trigger the development of the pathology associated with PD. Models of the presymptomatic and early symptomatic stages of PD induced by MPTP have been used to analyze changes in transcriptome profile in brain tissues, to identify specific patterns and mechanisms underlying neurodegeneration in PD. The whole-transcriptome analysis in the brain tissues of the mice with MPTP-induced PD showed that striatum is involved in the pathogenesis in the earliest stages and the processes associated with vesicular transport may be altered. The expression profiles of the genes studied in the substantia nigra and peripheral blood confirm that lymphocytes from peripheral blood may reflect processes occurring in the brain. These data suggest that messenger RNA (mRNA) levels in peripheral blood may provide potential biomarkers of the neurodegeneration occurring in PD. The changes in expression at the mRNA and protein levels suggest that Snca may be involved in neurodegeneration and Drd2 may participate in the development of the compensatory mechanisms in the early stages of PD pathogenesis. Our data suggest that the brain cortex may be involved in the pathological processes in the early stages of PD, including the presymptomatic stage.

[Synthesis of monoamines by non-monoaminergic neurons: illusion or reality?]. / Synthèse de monoamines par des neurones non-monoaminergiques. Illusion ou réalité ?

In contrast to monoaminergic (MA-ergic) neurons possessing the whole set of the enzymes for MA synthesis from the precursor amino-acid, some, mostly peptidergic, neurons co-express only one of the enzymes of monoamine synthesis. They are widely distributed in the brain, being particularly numerous in ontogenesis and, in adulthood, under certain physiological conditions. Most monoenzymatic neurons possess one of the enzymes for dopamine (DA) synthesis, tyrosine hydroxylase (TH) or aromatic L-amino acid decarboxylase (AADC). TH and AADC are enzymatically active in a substantial number of monoenzymatic neurons, where they are capable of converting L-tyrosine to L-3,4-dihydroxy-phenylalanine (L-DOPA) and L-DOPA to dopamine (DA) (or 5-hydroxy-tryptophan, 5-HTP to serotonin), respectively. According to our data L-DOPA synthesized in monoenzymatic TH-neurons is released and taken up by monoenzymatic AADC-neurons for DA synthesis. Moreover, L-DOPA captured by dopaminergic neurons and serotoninergic neurons serves to stimulate dopamine synthesis in the former and to start DA synthesis in the latter. Cooperative synthesis of MAs is considered as a compensatory reaction under a failure of MA-ergic neurons, e.g. in neurodegenerative diseases like hyperprolactinemia and Parkinson's disease, which are developed primarily because of degeneration of DA-ergic neurons of the tuberoinfundibular system and the nigrostriatal system, respectively. Noteworthy, the neurotoxin-induced increase of prolactin secretion returns with time to a normal level due to the stimulation of DA synthesis by the tuberoinfundibular most probably monoenzymatic neurons. The same compensatory mechanism is supposed to be used under the failure of the nigrostriatal DA-ergic system that is manifested by an increased number of monoenzymatic neurons in the striatum of animals with neurotoxin-induced parkinsonism and in humans with Parkinson's disease. Expression of the enzymes of MA synthesis in non-monoaminergic neurons is controlled by intercellular signals such as classical neurotransmitters (catecholamines), etc. Thus, a substantial number of brain neurons express partly the monoaminergic phenotype, namely individual complementary enzymes of MA synthesis, serving to produce MAs in cooperation, which is considered as a compensatory reaction under the failure of MA-ergic neurons.

Tyrosine hydroxylase expression in the olfactory/respiratory epithelium in early sheep fetuses (Ovis aries).

Transient expression of tyrosine hydroxylase (TH, the first enzyme in catecholamine synthesis) has been shown in different brain and peripheral structures of various species. TH-immunoreactive neurons have been reported in the nasal region of human and rat fetuses migrating to the forebrain with GnRH neurons during embryogenesis. In the present study, immunohistochemical analysis and in situ hybridization were performed in fetal sheep and in vitro sheep embryo olfactory placode cultures to confirm this population in this species. On embryonic days 33 to 35, TH-immunoreactive cells as well as TH cDNA-hybridized cells were found in the olfactory and respiratory epithelium and were spatially separated from GnRH-immunoreactive neurons. In days 40 to 44 of gestation, TH-immunoreactive neurons were no longer observed in the olfactory epithelium, and TH-immunoreactive fibers were found on the trajectories of the olfactory nerves. At this stage, some TH-immunoreactive fibers were also labeled for GnRH. TH-immunoreactive cells were also found in primary cultures of olfactory placodes of fetal sheep at 10 to 18 days in vitro. Some of them coexpressed GnRH. These results imply that olfactory epithelium is also able to give rise to TH expressing cells in fetal sheep, but this expression is suppressed earlier in ontogenesis than in humans due to some unidentified factors not present in the primary cultures of olfactory placode. The role of TH expression remains unclear as in other previously described examples.

Noradrenergic regulation of galanin expression in the supraoptic nucleus in the rat hypothalamus. An ex vivo study.

Galanin is coexpressed with vasopressin and oxytocin in magnocellular neurons of the rat neuroendocrine hypothalamus. Various physiological stimuli, such as osmotic stimulation or lactation, that affect vasopressin and oxytocin expression and release also modulate galanin expression. Magnocellular neurons are highly innervated by noradrenergic inputs from the brainstem. The noradrenergic system plays a critical excitatory role in the activation of vasopressin-expressing and oxytocin-expressing neurons. Here, we have evaluated the possible regulation of Gal expression by noradrenaline in the magnocellular neurons of supraoptic nucleus in an ex vivo acute model of rat hypothalamic slices. The slices containing the supraoptic nucleus were incubated with 10(-4) M noradrenaline for 1 or 4 hr. The levels of galanin and galanin mRNA were estimated by semiquantitative immunohistochemistry and in situ hybridization, respectively. Our results show that the amount of galanin-immunopositive material in the cell bodies of the magnocellular neurons increased significantly after incubation with noradrenaline compared with control slices at the same time point and that this effect was more pronounced after 4 hr than after 1 hr. In situ hybridization showed that radiolabeling of the supraoptic nucleus with a radioactive galanin probe increased slightly after 1 hr of incubation and increased considerably after 4 hr of incubation with noradrenaline. Our study shows that galanin may be a target in the regulation of the hypothalamic magnocellular-neurohypophysial system by noradrenaline.