Gentle handling temporarily increases c-Fos in the substantia nigra pars compacta

Abstract

Dopaminergic neurotransmission is involved in the regulation of sleep. In particular, the nigrostriatal pathway is an important center of sleep regulation. We hypothesized that dopaminergic neurons located in substantia nigra pars compacta (SNpc) could be activated by gentle handling, a method to obtain sleep deprivation (SD). Adult male C57/BL6J mice (N = 5/group) were distributed into non-SD (NSD) or SD groups. SD animals were subjected to SD once for 1 or 3 h by gentle handling. Two experiments were performed. The first determined the activation of SNpc neurons after SD, and the second examined the same parameters after pharmacologically induced dopaminergic depletion using intraperitoneal reserpine (2 mg/kg). After 1 or 3 h, SD and NSD mice were subjected to motor evaluation using the open field test. Immediately after the behavioral test, the mice were perfused intracardially to fix the brain and for immunohistochemical analysis of c-Fos protein expression within the SNpc. The open field test indicated that SD for 1 or 3 h did not modify motor behavior. However, c-Fos protein expression was increased after 1 h of SD compared with the NSD and 3-h SD groups. These immunohistochemistry data indicate that these periods of SD are not able to produce dopaminergic supersensitivity. Nevertheless, the increased expression of c-Fos within the SNpc suggests that dopaminergic nigral activation was triggered by SD earlier than motor responsiveness. Dopamine-depleted mice (experiment 2) exhibited a similar increase of c-Fos expression compared to control animals indicating that dopamine neurons are still activated in the 1-h SD group despite the exhaustion of dopamine. This finding suggests that this range (2-5-fold) of neuronal activation may serve as a marker of SD.

Eff ect of a single asenapine treatment on Fos expression in the brain catecholamine-synthesizing neurons: impact of a chronic mild stress preconditioning

“…Th ese data demonstrate that the cell bodies of the mesocortical dopaminergic system origin are activated by stress in contrast to DA neurons innervating the striatum, indicating that the mesocortical dopaminergic neurons exhibit diff erent regulatory features than mesolimbic or nigrostriatal neurons (Deutch et al 1985). Similarly, selective increases in Fos protein expression in response to stressor has been reported in the ventral mesencephalon, where restraint stress for 30 min increased the number of DA neurons exhibiting Foslike immunoreactivity in the ventral tegmental area (VTA), but not in the substantia nigra or retrorubral fi eld (Deutch et al 1991) In the present study, however, the 21 days lasting CMS preconditioning alone had no signifi cant eff ect on the Fos expression in the SNC, SNR, and VTA, which might be explained by the possible adaptation of animals to the daily repeated mild disturbances, since increased Fos expression has been reported in the SNC of adult male C57/BL6J mice aft er a gentle handling used for the introducing of a sleep deprivation (Santos et al 2008).…”

“…In the SNC, Fos expression increase has been demonstrated aft er 60 min of sleep deprivation induced by gentle handling, suggesting that dopaminergic nigral activation may be triggered by sleep deprivation (SD) earlier than motor responsiveness (Santos et al 2008 (Bontempi and Sharp 1997). Expression of Fos in transmitters-characterized neurons aft er stress (corticotropin-releasing factor/ catecholamine neurons/paraventricular nucleus/medulla oblongata/colchicine) has also been monitored (Ceccatelli et al 1989).…”

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus

“…Furthermore, our data demonstrated that the pathological mechanisms involved in locomotor hyperactivity in rats submitted to pilocarpine-induced SE were not affected by acute sleep deprivation. In fact, TSD did not induce hyperactivity in mice and longer periods of PSD were required to produce behavioral alterations [1,19]. It is important to mention that, even with the absence of effect of sleep deprivation; locomotor activity is a final parameter resulting from a complex process and may not be sufficiently sensitive for this approach.…”