Brain Monoamine Research Articles

Effects of Sex and Group Size on Behavior and Brain Biogenic Amines in Short-Lived Turquoise Killifish (Nothobranchius furzeri).

Short-lived turquoise killifish (Nothobranchius furzeri) becomes a popular model species for neuroscience. However, the effects of sex and rearing conditions on behavior and brain monoamines in N. furzeri are unknown. In this article, we study the body mass, behavior in the novel tank diving test, levels of noradrenaline (NA), dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) in the brain of 108 day-old N. furzeri males and females reared in small (one male and one or two females in 4-L tanks) and large (four males and four females in 25-L tanks) groups. Males were heavier and had a lower NA level in the brain compared with females. The behavior of males and females did not differ in the novel tank diving test. Their DA, 5-HT, DOPAC, and 5-HIAA levels in the brain did not differ too. Males from small groups spent more time near the tank's bottom. Rearing in small groups reduced the DA level in the female brain and the DOPAC level in female and male brains. However, group size did not affect body mass, 5-HT and 5-HIAA levels in the brain. Thus, group size is important for behavior and neuroscience studies of N. furzeri.

Antidepressant-like effect of dehydrozingerone from Zingiber officinale by elevating monoamines in brain: in silico and in vivo studies

BackgroundDehydrozingerone (DHZ) is an active ingredient of Zingiber officinale and structural half analogue of curcumin. In the present study, DHZ was evaluated for monoamine oxidase (MAO) inhibitory activity in silico and antidepressant activity in vivo.MethodThe binding affinity of DHZ with MAO-A (PDB ID: 2Z5Y) was assessed using Schrodinger's Maestro followed by free energy calculation, pharmacokinetic property prediction using Qikprop and Molecular dynamics simulation using Desmond. In vivo antidepressant activity of DHZ was evaluated on C57 BL/6 male mice using Escilatopram as the standard antidepressant. Open field test (OFT), forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant effect of the drugs on days 1 and 7. Following the behavioural study, neurotransmitters (noradrenaline, dopamine and serotonin) were estimated using liquid chromatography–mass spectrometry.ResultsDHZ demonstrated a greater binding affinity for the MAO-A enzyme compared to moclobemide in silico. Immobility in TST and FST were significantly (p < 0.05) reduced in vivo with 100mg/kg DHZ as compared to respective controls. DHZ treatment was more effective 1 h post treatment compared to vehicle control. A significant increase in levels of neurotransmitters was observed in mice brain homogenate in response to DHZ treatment, reassuring its antidepressant-like potential.ConclusionDHZ demonstrated MAO-A inhibition in silico, and the increased neurotransmitter levels in the brain in vivo were associated with an antidepressant-like effect.

Antidepressant-like Effects of Polygonatum humile Fisch via Serotonergic System in Mouse Model: Involvement of the Serotonin Subunit 6 Receptor

Polygonatum humile Fisch is commonly called Sookjuk in Korea. The roots of P. humile are typically used in traditional medicine as an anti-rheumatic, demulcent, and sedative agent. The aim of this study was to evaluate the potential of the P. humile extracts to treat depression. Mice were administered P. humile water extract (PH) and were subjected to the forced swim test (FST), tail suspension test (TST), and open-field test (OFT). The levels of brain monoamines including serotonin (5-HT), norepinephrine, and dopamine were evaluated. In addition, the PH antidepressant-like effects were studied based on the regulation of 5-HT-mediated Ca2+ and extracellular signal-regulated kinase 1/2 (ERK1/2) in human 1321N1 cells stably expressing the 5-HT subunit 6 receptor (5-HT6). In FST and TST, PH (300 mg/kg) significantly reduced the immobility time without changing the locomotor activity in mice. In addition, PH enhanced the level of 5-HT in the mice brain. The results further indicated an inhibitory activity of PH on both the 5-HT6 receptor expression level and the 5-HT6 receptor dependent downstream signal pathway ERK1/2.These findings indicated antidepressant-like effects of PH as evidenced by decreased immobility time in mice through a 5-HT6 receptor antagonistic mechanism.

Embryonic Thermal Manipulation Affects Ventilation, Metabolism, Thermal Control and Central Dopamine in Newly Hatched and Juvenile Chicks.

The first third of incubation is critical for embryonic development, and environmental changes during this phase can affect the physiology and survival of the embryos. We evaluated the effects of low (LT), control (CT), and high (HT) temperatures during the first 5 days of incubation on ventilation (E), body temperature (Tb), oxygen consumption (O2), respiratory equivalent (E/O2), and brain monoamines on 3-days-old (3d) and 14-days-old (14d) male and female chickens. The body mass of LT animals of both ages and sexes was higher compared to HT and CT animals (except for 3d males). The heart mass of 14d HT animals was higher than that of CT animals. Thermal manipulation did not affect E, O2 or E/O2 of 3d animals in normoxia, except for 3d LT males E, which was lower than CT. Regarding 14d animals, the HT females showed a decrease in E and O2 compared to CT and LT groups, while the HT males displayed a lower O2 compared to CT males, but no changes in E/O2. Both sexes of 14d HT chickens presented a greater Tb compared to CT animals. Thermal manipulations increased the dopamine turnover in the brainstem of 3d females. No differences were observed in ventilatory and metabolic parameters in the 3d animals of either sexes, and 14d males under 7% CO2. The hypercapnic hyperventilation was attenuated in the 14d HT females due to changes in O2, without alterations in E. The 14d LT males showed a lower E, during hypercapnia, compared to CT, without changes in O2, resulting in an attenuation in E/O2. During hypoxia, 3d LT females showed an attenuated hyperventilation, modulated by a higher O2. In 14d LT and HT females, the increase in E was greater and the hypometabolic response was attenuated, compared to CT females, which resulted in no change in the E/O2. In conclusion, thermal manipulations affect hypercapnia-induced hyperventilation more so than hypoxic challenge, and at both ages, females are more affected by thermal manipulation than males.

High Stocking Density and Food Deprivation Increase Brain Monoaminergic Activity in Gilthead Sea Bream (Sparus aurata).

Simple SummaryFarmed fish must cope with different stressors during aquaculture procedures, such as high densities, fasting, transport, or air exposure during handling. The severity and timing of these stressors can produce important imbalances in the overall status of the animals, triggering several endocrine and physiological players. In this study, gilthead sea bream (Sparus aurata) juveniles were assigned to four experimental conditions: (1) fed at a low stocking density (LSD-F, 4 kg·m−3); (2) fed at a high stocking density (HSD-F, 40 kg·m−3); (3) food-deprived at LSD (LSD-FD); and (4) food-deprived at HSD (HSD-FD). This served to evaluate, both at the plasma and central (brain) levels, the role of several hormonal (cortisol and catecholamines) and monoamine (dopaminergic and serotonergic neurotransmitters) functionalities. Our results evidenced chronic stress exposure (i.e., a high stocking density and food deprivation) fallouts in the enhancement of the parameters related to the stress response, where monoaminergic activities in different brain regions served to reorganize the physiological response depending on the challenge applied.In teleosts, brain monoamines (dopamine and serotonin) participate in the early response to different acute stressors. However, little is known regarding their role during chronic stress. In a 2 × 2 factorial design, the influence of a high stocking density (HSD) and/or food deprivation (FD) on the brain monoaminergic activity in gilthead sea bream (Sparus aurata) was evaluated. Following a 21-day experimental design, samples from the plasma and brain regions (telencephalon, hypothalamus, and optic tectum) were collected. The dopamine (DA), serotonin (5HT), and their main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5 hydroxyindoleacetic acid (5HIAA), contents were HPLC-assessed in brain tissues, and the ratios DOPAC/DA and 5HIAA/5HT were calculated as indicators of enhanced monoaminergic activity. The plasma levels of cortisol and catecholamine were also evaluated. The cortisol levels increased in fish exposed to HSD and normally fed but, also, in all FD groups, whereas the NA levels decreased in LSD-FD animals. Within the brain, the dopaminergic and serotonergic activities in telencephalon and hypothalamus increased in fish subjected to HSD and in the telencephalon of LSD-FD fish. While DA (hypothalamus) and 5HT (telencephalon) increased in the animals submitted to a HSD, food-deprived fish did not show such an increase. Taken together, our results supported the hypothesis of brain monoaminergic activity participating in maintaining and orchestrating the endocrine response to chronic stress in fish.

Activation of monoaminergic system contributes to the antidepressant- and anxiolytic-like effects of J147

Major depressive disorder (MDD) is a severe mental disorder, which is closely related to the deficiency of monoamine neurotransmitters. Our previous study suggested that acute treatment with J147, a novel curcumin derivative, produced antidepressant-like effects in mouse model of depression by regulation of 5-HT receptor subtypes. However, it is still unknown whether the antidepressant-like effects of J147 are involved in activation of central monoaminergic system. In this study, a series of classical behavior tests were employed to assess the involvement of monoaminergic system in antidepressant- and anxiolytic-like effects after sub-acute treatment of mice with J147 for 3 days. The results suggested that J147 at 10 mg/kg significantly reduced the immobility time in both the tail suspension and forced swimming tests, but didn’t show effects in the sucrose preference test. Similarly, sub-acute treatment of J147 did not induce amelioration in novelty suppressed feeding test. J147 increased duration and crossing time in the central area, but did not show significant change in rearing counts in the open field test. In neurochemical assays, studies suggested that serotonin and noradrenaline levels were significantly increased in the frontal cortex and hippocampus after treatment of J147 by the high-performance liquid chromatography (HPLC) with an electrochemical detector. Moreover, J147-induced significant inhibition of monoamine oxidase A activity. These findings suggest that the antidepressant- and anxiolytic-like effects of J147 might be related to the monoaminergic system by the evidence that high dose of J147 inhibits monoamine oxidase (MAO)-A activity and increases synaptic monoamines in the mouse brain.

Natural antioxidants enhance the power of physical and mental activities versus risk factors inducing progression of Alzheimer's disease in rats

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disease that is exacerbated by social isolation (SI) and protein malnutrition (PM). Antioxidants, physical and mental activities (Ph&M) can maintain cognitive functions and protect against dementia. ObjectiveTo investigate the impact of Epigallocatechin-3-gallate (EGCG), Vitamin E (VE), Vitamin C (VC), and Selenium (Se), in enhancing the potential effect of Ph&M versus SI&PM as risk factors in the progression of AD in rats. MethodsAluminum chloride (70 mg/kg, I.P for 5 weeks) was used to induce AD in rats that either normally fed or socially isolated and protein malnourished (SI&PM). Simultaneously, rats were weekly exposed to Ph&M either alone or in combination with EGCG (10 mg/kg, I.P), VC (400 mg/kg, P.O), VE (100 mg/kg, P.O), and Se (1 mg/kg, P.O). ResultsThe combination protocol of EGCG, VE, VC, and Se together with Ph&M significantly increased brain monoamines, superoxide dismutase (SOD), total antioxidant capacity (TAC) and brain-derived neurotrophic factor (BDNF) in AD, SI&PM and SI&PM/AD groups. Additionally, this regimen significantly mitigated brain acetylcholine esterase (ACHE), β-amyloid (Aβ), Tau protein, β-secretase, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and Interleukin 1β (IL-1β) as well as DNA fragmentation. These biochemical findings were supported by the histopathological examinations of brain tissue. ConclusionThe combination protocol of antioxidants with Ph&M activities mitigated SI&PM-induced progressive risk of AD.

Effects of caloric restriction on monoaminergic neurotransmission, peripheral hormones, and olfactory memory in aged rats

Aging is associated with a reduced ability to identify and discriminate scents, and olfactory dysfunction has been linked to preclinical stages of neurodegenerative diseases in humans. Moreover, emerging evidence suggests that smell-driven behaviors are regulated by hormones like insulin or leptin, and by metabolic parameters like glucose, which in turn may influence monoaminergic neurotransmission in brain areas related to cognition. Several studies have suggested that dietary interventions like caloric restriction (CR) can mitigate the age-induced decline in memory by modifying metabolic parameters and brain monoaminergic levels. The present study explored the effects of CR on age-dependent olfactory memory deficits, as well as their relationship with peripheral leptin, insulin and glucose levels, and brain monoamines. To this end, aged rats (24-months-old) fed on a CR diet or with ad libitum access to food, and adult rats (3–4 months), were trained in an odor discrimination task (ODT). The peripheral plasma levels of insulin, leptin, and glucose, and of monoamines and metabolites/precursors in brain areas related to olfactory learning and memory processes, such as the striatum and frontal cortex (FC), were determined. The data obtained indicated that CR attenuated the age-dependent decline in olfactory sensitivity in old animals fed ad libitum, which was correlated with the performance in ODT retention trial, as well as with leptin plasma levels. CR enhanced dopamine levels in the striatum, while it attenuated the age-related decline in serotonin levels in the striatum and FC. Such findings support a positive effect of CR on age-dependent olfactory sensitivity decline and dysfunctions in brain monoamine levels.

Effect of short- and long-term heat exposure on brain monoamines and emotional behavior in mice and rats

Heat exposure affects several physiological, neuronal, and emotional functions. Notably, monoaminergic neurotransmitters in the brain such as noradrenaline, dopamine, and serotonin, which regulate several basic physiological functions, such as thermoregulation, food intake, and energy balance, are affected by heat exposure and heat acclimation. Furthermore, cognition and emotional states are also affected by heat exposure and changes in brain monoamine levels. Short-term heat exposure has been reported to increase anxiety in some behavioral tests. In contrast, there is a possibility that long-term heat exposure decreases anxiety due to heat acclimation. These changes might be due to adaptation of the core body temperature and/or brain monoamine levels by heat exposure. In this review, we first outline the changes in brain monoamine levels and thereafter focus on changes in emotional behavior due to heat exposure and heat acclimation. Finally, we describe the relationships between emotional behavior and brain monoamine levels during heat acclimation.

Protocatechuic acid attenuates chronic unpredictable mild stress induced-behavioral and biochemical alterations in mice

Amelioration of oxidative stress via promoting the endogenous antioxidant system and enhancement of monoamines in brain were the important underlying antidepressant mechanism of protocatechuic acid (PCA). The aim of the present study is to explore the potential antidepressant mechanism(s) PCA in chronic unpredictable mild stress (CUMS) mice. Mice were subjected to CUMS protocol for 4 weeks, and administered with PCA (100 and 200 mg/kg) and fluoxetine (20 mg/kg) for 24 days (from day 8th to 31st). Behavioral (sucrose preference, immobility time, exploratory behavior), and biochemical alterations such as serum corticosterone, brain derived neurotrophic factor (BDNF), inflammatory cytokines, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), and antioxidants parameters were investigated. Experimental findings revealed that CUMS subjected mice exhibited significant impairment in behavioral alterations, such as increased immobility time, impaired preference to the sucrose solution, BDNF levels and, serum corticosterone, cytokines, malondialdehyde (MDA) formation with impaired antioxidants in the hippocampus and cerebral cortex. Administration of PCA to CUMS mice attenuated the immobility time, serum corticosterone, cytokines TNF-α, and IL-6, MDA formation and improved sucrose preference, including restoration of BDNF level. Thus, the present findings demonstrated the antidepressant potential of PCA which is largely achieved probably through maintaining BDNF level, and by modulation of the oxidative stress response, cytokines systems, and antioxidant defense system in mice.

Amphetamine Modulation of Long-Term Object Recognition Memory in Rats: Influence of Stress.

Amphetamine is a potent psychostimulant that increases brain monoamine levels. Extensive evidence demonstrated that norepinephrine is crucially involved in the regulation of memory consolidation for stressful experiences. Here, we investigated amphetamine effects on the consolidation of long-term recognition memory in rats exposed to different intensities of forced swim stress immediately after training. Furthermore, we evaluated whether such effects are dependent on the activation of the peripheral adrenergic system. To this aim, male adult Sprague Dawley rats were subjected to an object recognition task and intraperitoneally administered soon after training with amphetamine (0.5 or 1 mg/kg), or its corresponding vehicle. Rats were thereafter exposed to a mild (1 min, 25 ± 1°C) or strong (5 min, 19 ± 1°C) forced swim stress procedure. Recognition memory retention was assessed 24-h after training. Our findings showed that amphetamine enhances the consolidation of memory in rats subjected to mild stress condition, while it impairs long-term memory performance in rats exposed to strong stress. These dichotomic effects is dependent on stress-induced activation of the peripheral adrenergic response.

Behavioural and biochemical indications of the antidepressant activities of essential oils from Monodora myristica (Gaertn) seed and Xylopia aethiopica (Dunal) fruit in rats.

Monodora myristica and Xylopia aethiopica are two underutilised spices that are hypothesized to be important in the management and treatment of certain stress-induced diseases such as depression. The present study was designed to test the anti-depressant effects of the essential oils of Monodora myristica (EOMM) and Xylopia aethiopica (EOXA) and the possible underlying mechanisms in a chronic unpredictable mild stress (CUMS) - induced depression in the rat. Forty-two male Wistar rats were assigned to seven groups (n = 6); group I received corn oil (p.o, unstressed control), group II (stressed control) administered corn oil, groups III-IV received EOMM (150 & 300 mg/kg, p.o), groups V – VI received EOXA (150 & 300 mg/kg, p.o) whereas group VII had fluoxetine (10 mg/kg, p.o in d/w). Corn oil served as the vehicle for the delivery of the essential oils and the doses were administered via gastric intubation to rat once daily for six consecutive weeks from the 2nd week. Open-field, tail suspension (TST), and forced swimming (FST) tests were used to evaluate the behavioural activity in addition to the biochemical parameters (catalase, superoxide dismutase, reduced glutathione, monoamine oxidase, corticosterone, protein carbonyl compound, malondialdehyde and nitric oxide). The result showed that the administration of EOMM (150 and 300 mg/kg b.wt.) and EOXA (150 and 300 mg/kg b.wt.) during CUMS significantly ameliorated these behavioural activities and some biochemical parameters in rats. EOMM and EOXA exhibited significant antidepressant-like effects in a rat model of CUMS. At treatment doses of especially 300 mg/kg b.wt, the antidepressant effects of EOMM and EOXA are comparable to a standard antidepressant drug, fluoxetine (Prozac ™). The EOXA especially at a dose of 300 mg/kg b.wt is more effective than EOMM even at 300 mg/kg dose level in ameliorating depression in stressed rats. In conclusion, the study revealed that both the EOXA and EOMM relieved depression-like states through the mitigation of oxidative stress with a reduction in serum Corticosterone (CORT) and brain Monoamine Oxidase-A (MAO-A) levels.

The Effect of LPS and Ketoprofen on Cytokines, Brain Monoamines, and Social Behavior in Group-Housed Pigs.

Poor health is a risk factor for damaging behaviors, but the mechanisms behind this link are unknown. Injection of pigs with lipopolysaccharide (LPS) can be used to model aspects of poor health. Recent studies have shown that LPS-injected pigs perform more tail- and ear-directed behavior compared to saline-injected pigs and suggest that pro-inflammatory cytokines may play a role in these behaviors. The aims of this study were to test the effect of LPS on the social behavior of pigs and the neurotransmitters and modulators in their brains and to test the effect of a nonsteroidal anti-inflammatory drug on the effects of LPS. Fifty-two female pigs (11–12 weeks) were allocated to four treatments comprising two injections: saline–saline (SS), saline–LPS (SL), ketoprofen–saline (KS), and ketoprofen–LPS (KL). Activity was scan-sampled every 5 min for 6 h after the last injection in the pen. Social behavior was observed continuously in 10 × 15-min bouts between 8 a.m. and 5 p.m. 1 day before (baseline) and 1 and 2 days after the injection. Saliva was analyzed for cortisol and plasma for tryptophan and kynurenine. The frontal cortex, hippocampus, hypothalamus, and brain stem were sampled 72 h after the injection and analyzed for cytokines and monoamines. LPS activated the HPA axis and decreased the activity within 6 h after the injection. Ketoprofen lowered the effect of LPS on cortisol release and attenuated the behavioral signs of sickness in challenged pigs. SL pigs manipulated the ears of their pen mates significantly longer than SS pigs 2 days after the injection. LPS had no observed effect on IFN-γ, TNF-α, and IL-18. At 72 h after the injection, plasma tryptophan was depleted in SL pigs, and tryptophan and kynurenine concentrations in the frontal cortex and brain stem of SL pigs were significantly lower compared to those in SS pigs. Dopamine concentrations in the hypothalamus of SL pigs were significantly lower compared to those in SS pigs. Serotonin concentrations in the hypothalamus and noradrenaline concentrations in the hippocampus of SL pigs were significantly lower compared to those in KL pigs. In conclusion, LPS influenced the different neurotransmitters and modulators in the brain that are hypothesized to play an important role in the regulation of mood and behavior.

Dokosaheksaenoična kiselina moduliše oksidativni stres i nivo monoamina u mozgu miševa sa dijabetesom izazvanim streptozotocinom

The prevalence of diabetes mellitus (DM) is increasing in many countries. A lower prevalence of DM type 2 and other glucose metabolism disorders was observed in populations consuming larger amounts of n-3 polyunsaturated fatty acids, existing mainly in fish. Docosahexaenoic acid (DHA) is an important signaling molecule required for the central nervous system continuous maintenance of brain functioning. The aim of this research is to highlight the role of DHA in controlling glycemic measures and modulating the oxidant/antioxidant status and levels of neurotransmitters in brains of diabetic rats. Diabetes was induced with a single s.c. injection of streptozotocin (STZ) (6.0 mg/0.5 ml/100 g body weight). Experimental male Wister rats (n=40) were randomly divided into four groups: control group, DHA, STZ-diabetic, and STZ + DHA. All rats were decapitated after 30 days to evaluate glucose and insulin levels, brain oxidative stress and also to estimate monoamines levels. DHA administration significantly improved fasting blood glucose and insulin levels compared to the DHA+STZ group and decreased 8-hydroxy-2'-deoxyguanosine level in their urine. In addition, DHA treatment to STZ-treated rats showed a decrease in malondialdehyde content and advanced oxidation protein product and significantly increased glutathione content in brains of DHA + STZ-treated rats, and decreased the level of monoamines in rat's brain. To conclude: DHA modulated the elevated oxidative stress and neurotransmitters levels, and also acetylcholinesterase activity in diabetic rat brain via enhancing insulin level in serum

Adipose-derived mesenchymal stem cells rescue rat hippocampal cells from aluminum oxide nanoparticle-induced apoptosis via regulation of P53, Aβ, SOX2, OCT4, and CYP2E1.

Mesenchymal stem cells (MSCs) possess a preventive capacity against free radical toxicity in various tissues. The present study aimed to demonstrate the reformative and treatment roles of adipose-derived MSCs (AD-MSCs) against severe toxicity in the hippocampal cells of the brain caused by aluminum oxide nanoparticles (Al2O3-NPs). Rats were divided into five experimental groups: an untreated control group, a control group receiving NaCl, a group receiving Al2O3-NPs (6 mg/kg) for 20 days, a group that was allowed to recover (R) for 20 days following treatment with Al2O3-NPs, and a Al2O3-NPs + AD-MSCs group, where each rat was injected with 0.8 × 106 AD-MSCs via the caudal vein. Oral administration of Al2O3-NPs increased the protein levels of P53, cleaved caspase-3, CYP2E1, and beta-amyloid (Aβ); contrarily, AD-MSCs transplantation downregulated the levels of these proteins. In addition, the AD-MSCs-treated hippocampal cells were protected from Al2O3-NPs-induced toxicity, as detected by the expression levels of Sox2 and Oct4 that are essential for the maintenance of self-renewal. It was also found that AD-MSCs injection significantly altered the levels of brain total peroxide and monoamine oxidase (MAO)-A and MAO-B activities. Histologically, our results indicated that AD-MSCs alleviated the severe damage in the hippocampal cells induced by Al2O3-NPs. Moreover, the role of AD-MSCs in reducing hippocampal cell death was reinforced by the regulation of P53, cleaved caspase-3, Aβ, and CYP2E1 proteins, as well as by the regulation of SOX2 and OCT4 levels and MAO-A and MAO-B activities.

Brain Plasma Membrane Monoamine Transporter in Health and Disease.

Precise control of monoamine neurotransmitter levels in the central nervous system (CNS) is crucial for proper brain function. Dysfunctional monoamine signaling is associated with several neuropsychiatric and neurodegenerative disorders. The plasma membrane monoamine transporter (PMAT) is a new polyspecific organic cation transporter encoded by the SLC29A4 gene. Capable of transporting monoamine neurotransmitters with low affinity and high capacity, PMAT represents a major uptake2 transporter in the brain. Broadly expressed in multiple brain regions, PMAT can complement the high-affinity, low-capacity monoamine uptake mediated by uptake1 transporters, the serotonin, dopamine, and norepinephrine transporters (SERT, DAT, and NET, respectively). This chapter provides an overview of the molecular and functional characteristics of PMAT together with its regional and cell-type specific expression in the mammalian brain. The physiological functions of PMAT in brain monoamine homeostasis are evaluated in light of its unique transport kinetics and brain location, and in comparison with uptake1 and other uptake2 transporters (e.g., OCT3) along with corroborating experimental evidences. Lastly, the possibility of PMAT's involvement in brain pathophysiological processes, such as autism, depression, and Parkinson's disease, is discussed in the context of disease pathology and potential link to aberrant monoamine pathways.

Effect of fluoxetine on seizures in rats with high susceptibility to audiogenic stress

The seizures, triggered by a loud sound in laboratory animals, are associated with the imbalance of the brain monoamines. Serotonin (5-HT) is regarded as one of the principal neurotransmitters to be involved in regulation of wide variety of physiological and psychological processes. Among the drugs that affect 5-HT synaptic transmission, the leading role is given to selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine. The aim of the study is to investigate the effects of fluoxetine on seizures in Wistar rats with high susceptibility to audiogenic stress. The study was performed on male Wistar rats. Before the experiments, the animals were tested for susceptibility to audiogenic seizures by exposure to a sound of 90-110 dB for 2 min in the soundproof box. The difference between congenital susceptibility to seizures served as a basis for dividing animals into two groups: Seizure-susceptible (SS) and seizure-tolerant (ST) rats. One hour before the experiment, the experimental animals were orally administered with fluoxetine, while the control rats were treated with distilled water. The effect of fluoxetine on the level of the biogenic amines in different regions of the brain was determined by enzyme-linked immunosorbent assay (ELISA). It has been shown that in 100% of the cases, the control SS rats, exposed to audiogenic stimulus, exhibited wild running around in circles and jumping as some of the signs of seizure responses that evolved into tonic-clonic seizures in 70% of the cases. As regards the experimental SS animals: Only in 60% of the cases (P<0.05), they exhibited wild running and flinch, which did not evolve into the tonic-clonic phase. Decreased manifestation of seizures in the experimental SS rats under acute administration of fluoxetine may be explained by highly distinctive repertoire and spatial distribution of 5-HT receptors in their brain structures in comparison to the ST rats. The study of the monoaminergic mechanisms of seizure generation is of practical importance due to the existence of pharmacological agents, which selectively affect the activity of the monoaminergic systems of the brain, as well as the metabolism of the monoamines synthesized by them.

Medicinal Properties of Asparagus

Asparagus ia a vegetable and a medicinal or traditional herb. It has many health benefits because of its pharmacological properties and the active ingredients responsible for its effectiveness against various illnesses. A few medicinal Properties are discussed below:&#x0D; Anti-Inflammation Property of Asparagus&#x0D; Anti-inflammation can be defined as “It acts on body responses and reduce the inflammation, without directly counteracting the active agent such as glucocorticoids and aspirin”. One of these saponins has been of unique exuberance for relationship to amyotrophic horizontal sclerosis, otherwise called Lou Gehrig's Disease [1]. Even however amyotrophic parallel sclerosis is delegated a perpetual, neurodegenerative illness and isn't right now acknowledged as an immune system issue, over the top, undesirable irritation may assume an imperative part in the passing of certain nerve cells in amyotrophic sidelong sclerosis. In this mitigating setting, it is important that current research on the shatavarins in asparagus has uncovered another assemblage of saponins that impact aggravation through cytokine informing [2].&#x0D; Asparagus as the Best Antioxidant&#x0D; Analysts in Brazil has estimated the general reinforcement limit of asparagus. These specialists broke down twenty three ordinarily eaten vegetables in Brazil including asparagus. Their general outcomes demonstrated turmeric, watercress, lettuces, and broccoli to give the best general cancer prevention agent limit. Be that as it may, in a portion of the vegetables testing, asparagus turned out in the best ten among each of the twenty three vegetables for general cancer prevention agent limit. This finding isn't astonishing, given thenumerous customary and offbeat cell reinforcements show in asparagus. It merits recollecting here that asparagus positions as an astounding wellspring of both vitamin E and vitamin C two spotlight antioxidantas well as the mineral selenium, which assumes a key part in the capacity of glutathione peroxidase a standout amongst the most-examined cell reinforcement proteins in the body [3].The impact of methanolic concentrate of Asparagus pubescens was explored on compound, warm actuated agony and new egg whites incited aggravation. The concentrate measurement conditionally pent-up acidic corrosive incited wiggling, formalin-initiated torment licking and hot plate-actuated agony in mice. The concentrate essentially hindered the new egg whites prompted irritation in rats also. These hindrances were measurably critical [4].&#x0D; Antidepressant Activity&#x0D; The methanolic extract of asparagus demonstrated a decrease in immobility time in FST and TST in mice, which was comparable to imipramine and increase the levels of dopamine in vitro [5]. Futhermore, it was found to significantly brain monoamine oxidase levels as compared to control in a study focusing on finding the underlying mechanism of action, it was seen that methanolic extracts significantly inhibited cholinesterase and MAO activities [6]. In another study, antidepressant like activity was seen with methanolic root extract in FST and learned helplessness model [7].&#x0D; Anti Amnesic Activity&#x0D; Ethanolic root extract of asparagus was observed to produce a significant dose dependent enhancement of memory in the elevated plus maze model in mice [8]. The effect being significantly higher then the produced by piracetam [9]. Also there was an increase in the acetylcholinestrease levels in hippocampus areas associated with learning and memory [10]. In another study, methanolic exracts was found to reverse amnesia produced by scopolamine and sodium nitrate in the EPM and Morris water maze model in mice [11].&#x0D; Analgesic Action&#x0D; Aqueous and alcohalic root extracts of asparagus has been found to produce indicative analgesic action in heat conduction model. In another study, ethanolic extracts of asparagus was found to inhibit writing reflex in acetic acid induced writing model in mice [12].&#x0D; Antipyretic Action&#x0D; The ethanolic extracts of asparagus showed significant more antipyretic activity in albino Wistar rats than the aqueous extract in the yeast-derived pyrexia model, an effect comparable to normal antipyretic paracetamol [13]. Asparagus root extract which contains highest amount of flavonoids, polyphenols and vitamin-C exhibits the greatest antioxidant activity. Asparagus is likewise rich in flavonoid rutin&#x0D; REFERENCES

Semax, synthetic ACTH(4–10) analogue, attenuates behavioural and neurochemical alterations following early-life fluvoxamine exposure in white rats

Selective serotonin reuptake inhibitors (SSRI) are commonly used to treat depression during pregnancy. SSRIs cross the placenta and may influence the maturation of the foetal brain. Clinical and preclinical findings suggest long-term consequences of SSRI perinatal exposure for the offspring. The mechanisms of SSRI effects on developing brain remain largely unknown and there are no directional approaches for prevention of the consequences of maternal SSRI treatment during pregnancy. The heptapeptide Semax (MEHFPGP) is a synthetic analogue of ACTH(4–10) which exerts marked nootropic and neuroprotective activities. The aim of the present study was to investigate the long-term effects of neonatal exposure to the SSRI fluvoxamine (FA) in white rats. Additionally, the study examined the potential for Semax to prevent the negative consequences of neonatal FA exposure. Rat pups received FA or vehicle injections on postnatal days 1–14, a time period equivalent to 27–40 weeks of human foetal age. After FA treatment, rats were administered with Semax or vehicle on postnatal days 15–28. During the 2nd month of life, the rats underwent behavioural testing, and monoamine levels in brain structures were measured. It was shown that neonatal FA exposure leads to the impaired emotional response to stress and novelty and delayed acquisition of food-motivated maze task in adolescent and young adult rats. Furthermore, FA exposure induced alterations in the monoamine levels in brains of 1- and 2- month-old rats. Semax administration reduced the anxiety-like behaviour, improved learning abilities and normalized the levels of brain biogenic amines impaired by the FA exposure. The results demonstrate that early-life FA exposure in rat pups produces long-term disturbances in their anxiety-related behaviour, learning abilities, and brain monoamines content. Semax exerts a favourable effect on behaviour and biogenic amine system of rats exposed to the antidepressant. Thus, peptide Semax can prevent behavioural deficits caused by altered 5-HT levels during development.

Changes in Aggressive Behavior, Cortisol and Brain Monoamines during the Formation of Social Hierarchy in Black Rockfish (Sebastes schlegelii).

Simple SummaryBlack rockfish (Sebastes schlegelii) are naturally solitary animals. Under a high stocking density in aquaculture, juvenile black rockfish frequently show aggressive interactions, resulting in welfare issues (e.g., body injury). Aggressive interactions can lead to a social hierarchy and influence the responses of animal behavior and physiology. However, the responses of fish behavior and physiology to social hierarchy is limited. This study examined the differences in the growth performance, aggression, cortisol level, brain serotonergic activity, and brain dopamine activity between the dominant individuals and the subordinate individuals in the short-term contest and in the long-term contest. Ultimately, our results suggest that subordinate hierarchy inhibits aggression but does not impact growth in black rockfish. The cortisol-related change in brain monoaminergic activity could be a potential indicator to predict aggressive behavior in black rockfish in captivity with an obvious social hierarchy. This study has provided new insight into the understanding of the regulatory mechanisms between social hierarchy and aggressive behavior in black rockfish, and contributed to building the theoretical basis for behavioral management to solve the welfare issues in captive fish.Aggressive interactions can lead to a social hierarchy and influence the responses of animal behavior and physiology. However, our understanding on the changes of fish behavior and physiology during the process of social hierarchical formation is limited. To explore the responses of fish behavior and physiology to social hierarchy, we examined the differences in the growth performance, aggression, cortisol level, brain serotonergic activity, and brain dopamine activity between the dominant individuals and the subordinate individuals of black rockfish (Sebastes schlegelii) in two time scenarios. In the short-term contest, the cortisol level and the ratio of telencephalic 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) was significantly higher in subordinate individuals than in dominant individuals. In the long-term contest, the ratios of 5-HIAA/5-HT in all brain regions were significantly higher, and the frequency of aggressive acts were significantly lower in subordinate individuals than in dominant individuals. In contrast, no difference was detected in growth performance. Significant positive correlations between the cortisol level and serotonergic activity were observed in the short-term contest, but the serotonergic activity was negatively correlated with the aggressive behavior in the long-term contest. These results suggest that subordinate hierarchy inhibits aggression but does not impact growth in black rockfish. The cortisol-related change in brain monoaminergic activity could be a potential indicator to predict aggressive behavior in black rockfish in captivity with an obvious social hierarchy.