Neuroanatomical Study of the A11 Diencephalospinal Pathway in the Non-Human Primate

BACKGROUND: The A11 diencephalospinal pathway is crucial for sensorimotor integration and pain control at the spinal cord level. When disrupted, it is thought to be involved in numerous painful conditions such as restless legs syndrome and migraine. Its anatomical organization, however, remains largely unknown in the non-human primate (NHP). We therefore characterized the anatomy of this pathway in the NHP. METHODS AND FINDINGS: In situ hybridization of spinal dopamine receptors showed that D1 receptor mRNA is absent while D2 and D5 receptor mRNAs are mainly expressed in the dorsal horn and D3 receptor mRNA in both the dorsal and ventral horns. Unilateral injections of the retrograde tracer Fluoro-Gold (FG) into the cervical spinal enlargement labeled A11 hypothalamic neurons quasi-exclusively among dopamine areas. Detailed immunohistochemical analysis suggested that these FG-labeled A11 neurons are tyrosine hydroxylase-positive but dopa-decarboxylase and dopamine transporter-negative, suggestive of a L-DOPAergic nucleus. Stereological cell count of A11 neurons revealed that this group is composed by 4002±501 neurons per side. A 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) intoxication with subsequent development of a parkinsonian syndrome produced a 50% neuronal cell loss in the A11 group. CONCLUSION: The diencephalic A11 area could be the major source of L-DOPA in the NHP spinal cord, where it may play a role in the modulation of sensorimotor integration through D2 and D3 receptors either directly or indirectly via dopamine formation in spinal dopa-decarboxylase-positives cells

Influence de la serotonine sur la différenciation des neurones à GnRH chez le rat et la souris pendant l'ontogenèse

PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

The influence of catecholamine on the migration of gonadotropin-releasing hormone-producing neurons in the rat foetuses

atecholamines (CA) play an important role inthe regulation of GnRH neurons in adults, and it is probablethat they control GnRH-neuron development. Migration ofGnRH neurons was evaluated in male and female rats at the17th embryonic day (E17) and E21, following the dailytreatment of their pregnant mothers from the 11th to the16th and 20th day of gestation witha-methyl-para-tyrosine(aMPT), an inhibitor of catecholamine synthesis. High-performance liquid chromatography with electrochemicaldetection (HPLC-ED) was used to specify theaMPT-induced CA depletion. There was a 50–70% decrease indopamine and noradrenaline content in the nose and in thebrain ofaMPT-treated foetuses, proving the efficacy of thispharmacological model. Immunohistochemistry was usedto evaluate the percentage (%) of GnRH neurons alongtheir migration pathway from the vomeronasal organ(VNO) in the nose to the septo-preoptic area in the fore-brain which is considered as an index of neuron migration.Special attention was paid to the topographic relationshipsof GnRH neurons with catecholaminergic fibres. Thesewere observed in apposition with GnRH neurons in theentrance to the forebrain. In CA-deficient foetuses, thepercentage of GnRH neurons located in the rostral regionsextending from the VNO to the septum was greater than incontrols. However, no statistically significant differencewas found in the forebrain which extended from the septumto the retrochiasmatic area. In conclusion, these data sug-gest that endogenous catecholamines stimulate the GnRHneuron migration in ontogenesis

Expression précoce de la tyrosine hydroxylase dans l'épithélium olfactif et respiratoire chez le foetus de mouton (Ovis aries)

National audienc

Plasma catecholamine levels in the early stages of treatment-naïve Parkinson’s disease

Rationale: Parkinson's disease (PD) is a neurodegenerative disorder with predominant involvement of catecholamine-producing neurons of the central and peripheral nervous system. Taking into account the relative availability and low costs of plasma catecholamine measurements, it is worthwhile to study these parameters as biomarkers of the early stages of PD.Aim: To determinate whether plasma levels of dopamine (DA), norepinephrine (NE), L-3,4-dihydroxyphenylalanine (DOPA) and dihydroxyphenylacetic acid (DOPAC) in patients with early stages of PD are related with akinetic-rigid and tremor-dominant variants and to compare the results to healthy volunteers.Materials and methods: This was an observational cross-sectional cohort study performed from 2012 to 2015. The main study group included unselected outpatients who attended the Republican Consultative and Diagnostic Center of Movement Disorders and Botulinotherapy (Kazan, Russia) with newly diagnosed early PD (Hoehn and Yahr stages I and II, 1967), of various ages and both genders, who had not been given any specific antiparkinsonian treatment. The control group included healthy volunteers with no clinical signs of PD (they could have other chronic diseases of the non-extrapyramidal origin). Plasma catecholamine levels were measured by gas liquid chromatography.Results: One hundred and thirty (130) treatment-naïve patients with newly diagnosed PD (mean age 59.34 ± 8.42 years, male gender 45.38%) were enrolled into the main study group. The control group included 56 healthy volunteers matched for age and gender. The distribution of various PD forms and stages was as follows: PD tremor-dominant variant 56.9%, PD akinetic-rigid variant 43.1%; PD stage I 76.9%, PD stage II 23.1%. Irrespective of the variant and stage, the PD patients demonstrated decreased NE levels, compared to the controls (95% confidence intervals 124–216 and 248–428 pg/mL, respectively, р < 0.026). DOPA plasma level was reduced only in the patients with akinetic-rigid PD variant (р = 0.017), while DOPAC level in the patients with PD stage II (р = 0.008). The average DA:NE:DOPA:DOPAC ratio was 1:32:105:64 in the control group, 1:62:238:88 in the patients with PD tremor-dominant variant (the difference is significant for NE and DOPA, р < 0.05), and 1:29:96:32 in those with PD akinetic-rigid variant (p > 0.05). In the healthy controls the changes in DOPA levels account for 84% of the DA and NE variability; no correlation between DOPAC and other catecholamines was found. On the contrary, in the PD patients regardless of the stage and the disease variant, DOPAC levels directly correlated with DA (p < 0.04). The PD tremor-dominant variant patients demonstrated a direct correlation between plasma NE and DOPA levels (p < 0.05).Conclusion: The results obtained on absolute and relative parameters catecholamine turnover in the patients with early PD stages support the hypothesis on different pathophysiology of the tremor-dominant and akinetic-rigid variants of PD