Numerous studies suggest that the dopamine transporter (DAT), responsible for dopamine reuptake, may act as a vulnerability factor in the pathogenesis of Parkinson's disease (PD) and the vesicular monoamine transporter (VMAT2), responsible for its vesicular storage, as a neuroprotective factor. However, the relevance of each on the differential vulnerability of midbrain DA cells remains unknown. Here we studied the relationship between the expression pattern (mRNA and protein) of both transporters and the differential vulnerability of midbrain DA cells in a model of PD (intracerebroventricular injection of 6-OHDA in rats) and in monkey and human midbrain. Our results revealed that the expression patterns for VMAT2 mRNA and protein and DAT mRNA are similar, with the highest levels in the rostromedial region of substantia nigra (SNrm), followed by the caudoventral region of SN (SNcv), the ventral tegmental area and pigmented parabrabraquial nucleus (VTA/PBP), and finally the linear and interfascicular nuclei (Li/IF). In contrast, the expression of DAT protein in rats, monkeys, and humans followed a caudoventrolateral-to-rostrodorsomedial decreasing gradient (SNcv > SNrm > VTA/PBP > Li/IF), matching the degeneration profile observed after intracerebroventricular injection of 6-OHDA and in PD. In addition, DAT blockade made all midbrain DA cells equally resistant to 6-OHDA. These data indicate that DAT protein levels, but not DAT mRNA levels, are closely related to the differential vulnerability of midbrain DA cells and that this relationship is unaffected by the relative levels of VMAT2. Furthermore, the difference between DAT mRNA and protein profiles suggests internuclear differences in its posttransductional regulation.

Nitric oxide synthase (NOS) and interleukin-6 (IL-6) are constitutively expressed in hypothalamic cells. However, phenotypic and functional aspects of these cells remain unknown. We have studied the expression pattern of these two molecules in hypothalamic cells expressing corticotropin-releasing factor (CRF) and arginin-vasopressin (AVP), two major regulatory peptides in the hypothalamus-pituitary system, using immunofluorescence, intracerebroventricular injection of colchicine, and the study in parallel of the labeling pattern of axons in the median eminence. Within AVP cells, we distinguished two different populations: large, intensely stained AVP cells coexpressing IL-6; and large, intensely stained AVP cells coexpressing IL-6 and NOS. Within the CRF cells, we distinguished three different populations: large, intensely stained CRF cells immunonegative for AVP, NOS, and IL-6; large cells weakly stained for CRF and AVP, immunopositive for NOS and immunonegative for IL-6; and small cells intensely stained for CRF and AVP and immunonegative for IL-6 and NOS. In addition, we also found AVP cells containing IL-6 in the suprachiasmatic nucleus. These results suggest that neuronal NOS and IL-6 may be involved in different modulatory processes in hypophysiotropic and non-hypophysiotropic cells.

The fact that NOS upregulation is more evident in patients with a long seizure history suggests that this is a consequence of seizures, acting probably as an adaptative response to the sustained release of excitatory amino acids.

Proximal separation (PS) refers to isolating pups in small cages so dams can hear, smell, and see pups but have very limited physical contact with them. Six days of PS diminished the number of discernible oxytocin- (OT) immunostaining perikarya in forebrain areas of rat dams compared with 6 days of total separation (TS) or no separation (NS) from pups. Dams exhibited a more rapid resurgence of maternal behavior after 4-6 days of PS than after 4-6 days of TS. Bilateral infusion of the OT antagonist (OTA; 1 microgram/microliter/side) into the ventral tegmental area blocked the resurgence of maternal behavior after 3-6 days of PS but not after 2 days of PS or 4-6 days of NS. The conclusion was that PS for 3 or more days reinstates OT as necessary and sufficient for the activation of maternal behavior in experienced rat mothers. These findings suggest that some aspects of somatosensory stimulation from pups regulate the role of OT in the control of maternal behavior.