Brain DA Levels Research Articles

α-Mangostin exhibits antidepressant-like effects mediated by the modification of GABAergic, serotonergic and dopaminergic systems

The present study explored the antidepressant-like activity of α-mangostin (α-MG) and the possible mechanism in this process in the tail suspension test (TST) in mice. The results revealed that α-MG (5 mg/kg, i.p.) exhibited markedly antidepressant-like activity, which could be reversed by pretreatment with haloperidol (a non-selective D2 receptor antagonist), bicuculline (a competitive GABA antagonist), p-chlorophenylalanine (an inhibitor of 5-HT synthesis). Meanwhile, α-MG also effectively increased the brain DA, 5-HT and GABA levels in mice exposed to TST, indicating that the antidepressant-like effect of α-MG might be mediated by the GABAergic, serotonergic and dopaminergic systems.

Updates in the pathophysiological mechanisms of Parkinson's disease: Emerging role of bone marrow mesenchymal stem cells.

To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson's disease (PD) pathophysiology. MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done. BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs. The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.

Interactions of Gonadal Steroids with Brain Dopamine and Gonadotropin-Releasing Hormone in the Control of Gonadotropin-II Secretion in the Goldfish

In goldfish it is known that intraperitoneal implantation with testosterone (T) or estradiol (E 2) potentiates the serum gonadotropin-II (GtH-II) response to gonadotropin-releasing hormone (GnRH) without affecting basal GtH-II levels. Since the release of GtH-II in goldfish is under a tonic dopaminergic inhibitory tone, the possibility of sex steroids modulating brain and pituitary dopamine was examined in vivo and in vitro. Implantation of females with either T or E 2 (100 μg/g in solid silastic pellets) also potentiated the increase in serum GtH-II in response to the dopamine antagonist, domperidone (10 μg/g). High-performance liquid chromatography measurements showed that steroid implantation had no effect on dopamine content in the telencephalon including preoptic area, hypothalamus, and pituitary. However, the present study demonstrates that T or E 2 can increase pituitary dopamine turnover rates following tyrosine hydroxylase inhibition with α-methyl- p-tyrosine (240 μg/g). In vitro perifusion of pars distalis fragments from E 2- or T-treated fish also showed a potentiation of salmon GnRH (sGnRH)-induced GtH-II release compared to controls. However, exposure to pituitary fragments from control and steroid-treated fish to increasing doses of the dopamine agonist LY 171555 did not demonstrate a significant difference in the sensitivity of the gonadotrophs to dopamine. Testosterone-induced alterations in DA turnover are dissociable from the positive action of T on pituitary responsiveness, since the potentiating effect of T implantation was not affected by severe depletion of brain and pituitary DA levels by α-methyl- p-tyrosine pretreatment. These data demonstrate that in gonad-intact goldfish, sex steroids enhance pituitary responsiveness to GnRH but basal serum GtH-II levels are maintained by a concomitant increase in DA turnover in the pituitary.

Nicotinic acid or N-methyl nicotinamide prolongs elevated brain dopa and dopamine in L-dopa treatment.

A peripheral dopa decarboxylase inhibitor, benserazide, was given ip, followed by intubation with L-dopa. Brain dopa and DA levels were elevated maximally between 0.5-2.5 hr and 1.0-2.5 hr, respectively. Dopa in serum, liver, and brain were at control values after 4 hr. Supplementation of dopa with NAM or NAC, as possible methyl group acceptors to lower catabolism of DA, showed that NAM had no effect on DA levels or on SAM. However, with both NAC and N-methyl NAM (a methylated compound intended as a control) at time periods where dopa and DA were normally decreasing, the brain levels were increased over control values with benserazide and dopa alone. NAC or N-methyl NAM appeared to extend the period of elevated brain DA levels with L-dopa treatment. The mechanism responsible for these results is uncertain.

α-Melanocyte-stimulating hormone and behavior

Melanocyte-stimulating hormone (MSH) has putative adaptive significance in all forms of species where it is present. In mammals the polypeptide chain influences learning, memory and attention. Chemically MSH shares the first 13 (α-MSH) or the first 18 or 22 (β-MSH) amino acids with adrenocorticotropic hormone (ACTH), even though the mechanisms of secretion and behavioral effects are often quite different. The still shorter peptide chain MSH/ACH 4–10 demonstrates significant melanotropic and behavioral actions of α-MSH without showing any steroidogenic effect. Behaviorally, α-MSH and MSH/ACTH analogues (MSH/ACTH 4–9 and MSH/ACTH 4–10) influence the parameters of learning, attention and memory in both human and infrahuman subjects. α-MSH has also been reported to increase sensitivity and augment arousal mechanisms in the CNS. α-MSH has been observed to increase and sustain novelty-induced defecation, and this behavior was found to be accompanied by a concomitant decrease in whole brain DA and NE levels in both intact and hypophysectomized rats exposed daily to a test box. The behavioral effects of α-MSH may be partially modulated by the enhanced cyclic-AMP activity in the CNS observed after MSH administration. MSH also seems to be working in conjunction with the hypothalamic tripeptide MIF-1 and the pineal hormone melatonin, both of which can affect the release of MSH from the pituitary. Recent evidence suggests that MSH is counterbalancing against and complementing with the effects of endorphins, specifically β-endorphin (61–91 chain of β-LPH), in maintaining learning and attentive behaviors.

Age-related motor and catecholomine alterations in mice on levodopa supplemented diet

Old mice reared on regular diet show reduced motor activity, decreased basal adenylate cyclase, and increased MAO activities compared to adults. Brain DDC and COMT activities, DA, NE levels and DA-stimulated adenylate cyclase remained unchanged. By contrast, mice fed levodopa for life did not develop decreased motor activity with aging, lived about 50% longer, had slightly elevated whole brain DA and NE levels and failed to develop the expected rise in MAO activity with aging. Levodopa did not alter the number of dopaminergic and muscarinic cholinergic receptors or the adenylate cyclase activity in the striatum during aging. On levodopa, hepatic and renal DA, dopa, and HVA increased but the latter two returned to basal levels by mid life. In liver, DDC was unchanged but MAO tended to be higher in levodopa-fed mice. Thus, motor impairment is an age-related phenomenon in mice associated with selective alterations in brain dopaminergic systems, which may be prevented by dietary levodopa. Extracerebral tissues, through possibly adaptive metabolic mechanisms, play a significant role in regulating brain catecholamines during chronic administration of large doses of levodopa.

α-MSH, MIF-I and melatonin: Effects on novelty-induced defecation, plasma 11-OHCS and central catecholamines in rats

The pituitary-hypothalamo-pineal complex involving MSH, MIF-I and melatonin has been strongly emphasized in the adaptive mechanism of the animal. A series of experiments was conducted to investigate the effects of α-MSH, MIF-I and melatonin on novelty-induced defecation, step-down activity, plasma 11-OHCS levels and whole brain DA and NE concentrations over days of novelty×drug treatment. α-MSH consistently enhanced and sustained novelty-induced defecation, increased plasma 11-OHCS levels in the resting intact rats and in the novelty exposed hypophysectomized (hypox) rats, and decreased brain DA and NE levels in intact, hypox and sham-hypox rats. MSH did not increase plasma 11-OHCS in intact and sham-hypox rats during exposure to novelty. MIF-I significantly habituated novelty-induced defecation and increased brain DA and NE levels over 5 days of drug×novelty treatment. Melatonin, on the other hand, inhibited novelty-induced defecation, decreased plasma 11-OHCS and increased brain DA level over 5 days of melatonin×novelty treatment. MSH, MIF-I or melatonin did not show any significant effect on the step-down activity of the rats. The results suggest the possibility that central CAs may be implicated in the behavioral changes observed after α-MSH, MIF-I and melatonin administration and in the interaction of the pituitary-hypothalamo-pineal complex involving MSH, MIF-I and melatonin.

α-MSH effects on novelty-induced defecation, plasma 11-OHCS and whole brain catecholamines in hypophysectomized rats

The effect of hypophysectomy on novelty-induced defacation was found to be inhibitory in nature, but this effect was reversed by treatment with α-MSH. MSH-treated hypox rats maintained, over days, novelty-induced defecation and showed a significant elevation in plasma 11-OHCS levels, compared with the levels of control-injected counterparts. MSH treatment also reduced over Days 1 to 5 the whole brain DA and whole brain NE levels in hypox animals. Control-treated hypox rats, however, showed an increase in brain NE concentration which was significantly reduced by MSH treatment. Sham-hypox animals also sustained novelty-induced defecation after MSH treatment but did not show a significant rise in plasma 11-OHCS level. Whole brain DA and whole brain NE levels in sham-hypox rats were also reduced significantly by MSH treatment. The behavioral maintenance of defecation in hypox and sham-hypox rats seem to be concomitant with significant reductions in whole brain catecholamines.

Effects of MIF-I and melatonin on novelty-induced defecation and associated plasma 11-OHCS and brain catecholamines

In two experiments the effects were investigated of MSH-inhibiting factor-I (MIF-I) and of Melatonin on step-down latencies, defection, plasma 11-OHCS levels, whole brain DA and whole brain NE concentrations on Days 1, 3 and 5 of novelty exposure. Treatment with MIF-I led to a significant habituation of novelty-induced defecation over 5 days, whereas plasma 11-OHCS level was reduced only on Day 1. The concentrations of whole brain DA and whole brain NE also showed a significant increase over days of MIF-I and novelty treatment. Melatonin treatment, on the other hand, significantly inhibited novelty-induced defecation and reduced plasma 11-OHCS level on Day 5 of novelty exposure. Melatonin treatment led to a significant increase of whole brain DA in animals exposed to novelty for 5 days. Neither MIF-I nor Melatonin was found to significantly affect the step-down activity of treated animals. The overall results suggested a possible relationship between novelty-induced defecation and brain DA levels of MIF-I and Melatonin treated animals.

Neuronal degeneration in rat brain induced by 6-hydroxydopamine; a histological and biochemical study

6-OHDA injected into the cerebrospinal fluid of the rat causes a fall in brain NE and DA levels, accompanied by degeneration of neuronal perikarya in SN and in adjacent VTA and lateral tegmentum, and terminal degeneration in CP, NAcc and OT demonstrable by the Nauta-Gygax and Fink-Heimer silver methods. NE levels fell to 5% of normal 14 days after a high dose (200 μg + 400 μg) of 6-OHDA, and DA levels to 17%. Even the more moderate declines in catecholamine levels following 200 μg 6-OHDA were accompanied by florid argyrophilic neuronal degeneration. The location of the terminal degeneration is very similar to that of DA-containing terminals identified by use of the histofluorescence method for monoamines. The location of degenerating cell bodies in SN closely corresponds to that of perikarya found by the histofluorescence method to contain dopamine, but the distribution in tegmentum and VTA is more restricted. Occasional cell bodies were seen to degenerate in the locus coeruleus and a few other areas after high doses of 6-OHDA. A group of degenerating axons of unusual appearance was found, probably afferent to NAcc and OT. No degeneration was seen in areas in which NE-containing terminals have been reported, despite reports of electron microscopic evidence of bouton degeneration in such areas elicited by 6-OHDA, and despite the severe decline in brain NE content in the higher-dose group. Nor was any change seen in the infundibular nucleus and median eminence, regions in which DA-containing neurons have been reported. Electrolytic SN lesions cause dense terminal degeneration in CP indistinguishable from that caused by 6-OHDA injection into the CSF. Only sparse terminal degeneration appeared in CP if electrolytic SN lesions were placed in rats that had received 6-OHDA several weeks prior to surgery. Large SN lesions in such pretreated animals induce a tendency to turn in circles away from the lesioned side.