Brain Serotonin Concentrations Research Articles

3 The impact of early-life cecal microbiota transplantation on injurious behaviors in egg-laying chickens

Abstract Injurious behaviors in laying hens are a critical issue facing the poultry egg industry. Recent studies have shown that the gut microbiota influences host brain function and behavioral characteristics in humans and various animals. In laying hens, it has been reported that injurious behaviors (such as aggression, feather pecking and cannibalism) are associated with dysregulation of the microbiota-gut-brain axis. To further interrogate the role of the microbiota-gut-brain axis on bird behavior, we used two inbred layer chicken lines, 63 and 72 (line 72 displays more aggressive behavior), and transferred pooled cecal contents from either line to day of hatch chicks. Cecal microbiota transplantation (CMT) from each line was conducted once daily, by gavage, from d 1 to 10, then boosted once weekly from wk 3 to 5. We hypothesized that the cecal microbiota composition and animal behavior in recipient birds would be similar to that of their donor animals because of the microbiota-gut-brain axis. Microbial communities were compared using 16S rRNA gene amplicon sequencing, behavior was recorded in home cages as well as in paired aggression tests, and physiological measurements were taken from brain tissue and blood to measure levels of neurotransmitters and immune function. When examining the differences in the donor birds, hypothalamic serotonin and tryptophan concentrations were greater for line 63 compared with line 72 birds (P < 0.05). Plasma corticosterone, heterophil/lymphocyte ratios, and central norepinephrine concentrations were less for line 63 birds (P < 0.05). Cecal microbial diversity was not statistically different between the lines, but many bacterial taxa were differentially abundant between the two lines. After cecal transplantation, 63-CMT (recipient) birds displayed less aggressive behavior with a greater hypothalamic serotonergic activity at wk 5, similar to donor birds. Correspondingly, two amplicon sequence variants (ASVs) belonging to Lachnospiraceae and one Ruminococcaceae UCG-005 ASV were positively correlated with the concentrations of brain tryptophan and serotonin, respectively. Along with greater aggression, 72-CMT birds seemed to have greater physical growth traits (increased body weight, ileal villus/crypt; P ≤ 0.05), but decreased concentrations of brain norepinephrine and dopamine, and the greatest ileal serotonin turnover in the ileum at wk 5 (P < 0.05). ASVs belonging to Mollicutes RF39 and GCA-900066225 in 72-CMT birds were negatively correlated with the brain 5-hydroxyindoleacetic acid (5-HIAA) at wk 5, and one Bacteroides ASV was negatively correlated with plasma serotonin at wk 16. Meanwhile, 63-CMT birds potentially had better gut health and immune function (greater concentrations of ileal mucosal secretory IgA, plasma IL-10; P < 0.05). These results suggest linkages among serotonergic activity, stress response, innate immunity, and gut microbiota populations and that CMT could be a novel strategy for reducing aggressive behavior through regulating signaling along the microbiota-gut-brain axis.

Novel Phytosomal Formulation of Emblica officinalis Extracts with Its In Vivo Nootropic Potential in Rats: Optimization and Development by Box-Behnken Design

Purpose. The present study aimed to improve the aqueous solubility, permeability, bioavailability, and nootropic potential of standardized Emblica officinalis extract (EOE) by developing a novel phytosomal formulation. Method. Emblica officinalis extract-loaded phytosomes (EOPs) were prepared using solvent evaporation. The EOP was prepared at different molar ratios of extract and phospholipid. Herein, the effects of phospholipid extract ratio (A), temperature (B), and reaction time (C) were systematically investigated on entrapment efficiency using Box-Behnken design. In vitro and in vivo characterizations of the optimized formulation were performed. Results. Optimized EOP formulation (89.90 ± 0.24 μg/ml) exhibited improved aqueous solubility than plain EOE (11.85 ± 0.25 μg/ml). The optimized formulation’s particle size and Zeta potential were 198.4 ± 0.20 nm and −39.0 ± 0.40 mv. DSC and XRD studies confirmed the partial amorphization of EOE in phytosomes. Optimized formulation exhibited 69.82 ± 0.17% of EOE release at 12 h and followed zero-order release kinetics. Moreover, the phytosomal formulation of EOE exhibited its rationality with an improvement of bioavailability by 2.7 folds compared with pure EOE. Compared to EOE, EOP showed significantly (p<0.05 lower escape and transfer latencies on both days in MWMT and EPMT, indicating more effective memory-enhancing activity. Furthermore, EOP-treated rats exhibited improved acetylcholine (Ach) levels than EOE. Brain tissue concentrations measured following EOP oral administration (1.06 ± 0.04 μg/ml) were substantially greater (p<0.05) than those following EOE (0.32 ± 0.07 μg/ml). The brain dopamine and serotonin concentration were found to be higher (16.27 ± 1.209 and 43.28 ± 1.550 ng/ml) in the EOP-treated group as compared to the pure extract-treated group (10.40 ± 1.185 and 32.79 ± 1.738 ng/ml). Conclusion. Improvement of aqueous solubility, permeability, dissolution, bioavailability, and narrower particle size distribution could facilitate enhancement in the nootropic potential of EOE phytosomal formulation.

The anticonvulsant effect of saiga horn on febrile seizures by regulating brain serotonin content and inhibiting neuroinflammation

Ethnopharmacological relevanceSaiga antelope horn (SAH) is derived from the Saiga antelope (Saiga tatarica Linnaeus) of the bovidae family. SAH has been used for the treatment of febrile seizures (FS) in children for thousands of years in China. Due to the biological protection of Saiga antelope and its ethical reasons, the application of SAH has been widely restricted. Unfortunately, the field of artificial manufacturing of SAH is still blank at present. The mechanism of SAH in the treatment of FS is still unclear, which seriously hinders the further development of artificial antelope horns and the search for substitutes for SAH. At present, there is an urgent need to determine the mechanism of SAH in the treatment of FS, so as to provide a theoretical basis for artificial antelope horn and its substitutes. Aim of the studyTo explore the anti-FS effect of natural SAH on FS rat model and its possible mechanism, and to provide a theoretical basis for the subsequent manufacture of artificial antelope horns and the search for the best substitutes. Materials and methodsFS was induced by a warm water bath (48 ± 0.5 °C). The latency and seizure grade of FS were observed and recorded. Hematoxylin-eosin (HE) staining was used to observe the functional defect of hippocampal cells. The contents of tryptophan (TRP), serotonin (5-HT), IL-1β and TNF-a in rat brain tissue were determined by ELISA. qRT-PCR and Western blot were used to detect the expression of 5-HT synthesis related neurotransmitter receptors, catalytic enzymes and inflammatory factors in hippocampus. Immunofluorescence was used to observe the expression of TPH2 protein in the dorsal raphe nucleus of rat brain. ResultsAfter pretreating rats with SAH, the seizure grade of FS was significantly reduced and the latency was prolonged. SAH can reduce the histological damage of hippocampal tissue induced by FS in rats. Further analysis of ELISA results showed that SAH significantly increased the levels of TRP and 5-HT in the brain of FS rats, and significantly decreased the levels of IL-1β and TNF-a. The results of QPCR showed that SAH could up-regulate the expression of ER-β and TPH2 mRNA and down-regulate the expression of IL-1β and TNF-ɑ mRNA in the hippocampus of rats. In addition, WB and immunofluorescence results showed that SAH could significantly up-regulate the expression of ER-β/TPH2/5-HT pathway in the hippocampus of FS rats and the expression of TPH2 protein in the raphe nucleus, but had no significant effect on SERT protein in the hippocampus of FS rats. In addition, ER-β protein inhibitor PHTPP significantly inhibited the therapeutic effect of SAH on FS rats. ConclusionsThe present study demonstrates that SAH has a significant anticonvulsant effect on the FS rat model. The mechanism may be related to the increase of TRP content and up-regulation the expression of ER-β/TPH2/5-HT signaling pathway in the brain of FS rats, thereby increasing the content of 5-HT in the brain and reducing the content of IL-1β and TNF-a in the brain.

Unraveling the periprandial changes in brain serotonergic activity and its correlation with food intake-related neuropeptides in rainbow trout Oncorhynchus mykiss.

This study explored changes in brain serotonin content and activity together with hypothalamic neuropeptide mRNA abundance around feeding time in rainbow trout, as well as the effect of one-day fasting. Groups of trout fed at two (ZT2) and six (ZT6) hours after lights on were sampled from 90 minutes before to 240 minutes after feeding, while additional groups of non-fed trout were also included in the study. Changes in brain amine and metabolite contents were measured in hindbrain, diencephalon and telencephalon, while in the diencephalon the mRNA abundance of tryptophan hydroxylase (tph1, tph2), serotonin receptors (5htr1a, 5htr1b and 5htr2c) and several neuropeptides (npy, agrp1, cartpt, pomca1, crfb) involved in the control of food intake were also assessed. The results showed changes in the hypothalamic neuropeptides that were consistent with the expected role for each in the regulation of food intake in rainbow trout. Serotonergic activity increased rapidly at the time of food intake in the diencephalon and hindbrain and remained high for much of the postprandial period. This increase in serotonin abundance was concomitant with elevated levels of pomca1 mRNA in the diencephalon, suggesting that serotonin might act on brain neuropeptides to promote a satiety profile. Furthermore, serotonin synthesis and neuronal activity appear to increase already before the time of feeding, suggesting additional functions for this amine before and during food intake. Exploration of serotonin receptors in the diencephalon revealed only small changes for gene expression of 5htr1b and 5htr2c receptors during the postprandial phase. Therefore, the results suggest that serotonin may play a relevant role in the regulation of feeding behavior in rainbow trout during periprandial time, but a better understanding of its interaction with brain centers involved in receiving and processing food-related signals is still needed.

ANTIMIGRAINE ACTIVITY OF METHANOLIC EXTRACT OF ABROMA AUGUSTA L. IN LABORATORY ANIMALS

Objective: The present study aimed to evaluate of antimigraine activity of methanolic extract of Abroma augusta L. leaves in laboratory animals. Methods: The antimigraine activity was evaluated against nitroglycerine (NTG, 10 mg·kg−1, i. p.) and bradykinin (BK, 10 µg, intra-arterial) induced hyperalgesia in rats. Rats were divided randomly into six groups: normal, control, standard (sumatriptan, 42 mg·kg−1, s. c.), and Abroma augusta L. (100,200 and 400 mg·kg−1, p. o.). In the nitroglycerin (NTG) induced hyperalgesia model, rats were pre-treated with standard drug sumatriptan and Abroma augusta L. for 0, 7 and 14 d and tail flick latency were recorded separately in 0-day, 7-day and 14-day pretreatment study. Brain serotonin concentration was also estimated by HPLC method at the end of the study. In bradykinin induced hyperalgesia model the number of vocalizations were recorded as a measure of hyperalgesia in rats. Results: Abroma augusta L. showed a significant (P<0.001) elevation in the tail-flick latency (at dose 400 mg·kg−1) and body weight (at doses 100, 200, and 400 mg·kg−1) in NTG-induced hyperalgesia model in rats. Further, A. augusta L. (400 mg/kg) showed a significant (P<0.001) increase in brain serotonin concentration compared to NTG control group animal. It showed a significant (P<0.01, P<0.001) reduction in the elevated number of vocalizations at doses (200 and 400 mg·kg−1) in the bradykinin-induced hyperalgesia model in rats. Conclusion: We concluded that the methanolic extract of Aroma augusta L. possessed an anti-migraine effect in nitroglycerine and bradykinin-induced hyperalgesia model in rats.

An Early Disturbance in Serotonergic Neurotransmission Contributes to the Onset of Parkinsonian Phenotypes in Drosophila melanogaster.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor symptoms and dopaminergic cell loss. A pre-symptomatic phase characterized by non-motor symptoms precedes the onset of motor alterations. Two recent PET studies in human carriers of mutations associated with familial PD demonstrate an early serotonergic commitment—alteration in SERT binding—before any dopaminergic or motor dysfunction, that is, at putative PD pre-symptomatic stages. These findings support the hypothesis that early alterations in the serotonergic system could contribute to the progression of PD, an idea difficult to be tested in humans. Here, we study some components of the serotonergic system during the pre-symptomatic phase in a well-characterized Drosophila PD model, Pink1B9 mutant flies. We detected lower brain serotonin content in Pink1B9 flies, accompanied by reduced activity of SERT before the onset of motor dysfunctions. We also explored the consequences of a brief early manipulation of the serotonergic system in the development of motor symptoms later in aged animals. Feeding young Pink1B9 flies with fluoxetine, a SERT blocker, prevents the loss of dopaminergic neurons and ameliorates motor impairment observed in aged mutant flies. Surprisingly, the same pharmacological manipulation in young control flies results in aged animals exhibiting a PD-like phenotype. Our findings support that an early dysfunction in the serotonergic system precedes and contributes to the onset of the Parkinsonian phenotype in Drosophila.

Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain.

Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six weeks of chronic unpredictable stress (depression group: n = 9, Lactobacillus intervention group: n = 7). L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly reduced depressive behaviour in the forced swimming test and tail suspension test, significantly reduced anxiety behaviour in the open field test, and reduced anxiety behaviour in the marble burying test and light/dark box test. L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly increased the brain serotonin and brain-derived neurotrophic factor concentrations, and CCFM1229 significantly decreased the serum corticosterone concentration, all of which are closely associated with the relief of depressive symptoms. Furthermore, CCFM1229 and CCFM1228 were shown to regulate purine metabolism in mice, as indicated by decreases in brain xanthine oxidase activity and an increase in liver adenosine deaminase activity. Anxiety- and depression-related indicators were significantly associated with xanthine oxidase activity in the cerebral cortex. The strains CCFM1229 and CCFM1228 reduced anxiety- and depression-related behaviour in a mouse model of chronic stress-induced depression, which may be achieved by regulating the activity of brain xanthine oxidase.

Comparative Neuroprotective Effect of Energy Drinks

Objective: The objective of this research was Comparative neuroprotective effect of energy drinks inmice using various experimental animal models.Method: The Tail suspension test (TST), Forced swim test (FST) and Y-maze test were used to assessthe antidepressant activity of the Energy drinks (Red bull, monster and enerzal) in mice. In addition,attempts have been conducted to explore the level of brain monoamine neurotransmitters like Dopamineand Serotonin using flame fluorimeter.Result: The study of energy drinks on the gross behaviour of mice indicated their CNS antidepressanteffect. Furthermore, their significant (p<0.0001) antidepressant property was estimated by obtainingits decreased immobility time of mice in tail suspension and forced swim tests. It has also exhibitedsignificant cognitive property performed in Y-maze apparatus. Biochemical study showed theirpotentiation in the brain dopamine and serotonin concentration significantly (p<0.001) in mice whichconcludes the mechanism behind their CNS depressant and cognitive propertiesConclusion: The gross behavioural study indicated their antidepressant potentiality which was furtherconfirmed by conducting FST and TST. Further the study showed the memory enhancement by theEDs using Y-maze apparatus but in lesser extent. Antidepressant drugs are well evident with propertyto increase dopamine and serotonin level and EDs were observed to potentiate significantly the braindopamine and serotonin concentration in mice.

Simultaneous administration of coffee and rasagiline/l-dopa protects against paraquat-induced neurochemical and motor behavior impairments in vivo

BackgroundCaffeine is a natural alkaloid present in a variety of highly consumed popular drinks such as coffee, tea and soft drinks as well as chocolate. Its consumption elicits beneficiary psychostimulant that has been linked to a reduced risk of developing Parkinson’s disease (PD). The aim of the present study is to investigate the possible synergistic neuroprotective effects of co-administration of caffeine (CAF) or coffee (COF) with rasagiline (R) or l-dopa against paraquat (PQ)-induced neurochemical and motor behavior impairments in mice.ResultsIn behavioral tests, R + COF increased the locomotor activity in rotarod test compared to l-dopa + COF. l-Dopa combinations decreased the immobility time in FST compared to rasagiline combinations; l-dopa + CAF provided a similar increase in locomotor activity compared to R + CAF. Combination of CAF or COF with l-dopa or rasagiline resulted in a substantial improvement in brain neurotransmitter and antioxidant levels as they significantly increased dopamine and super oxide dismutase but significantly decreased nitric oxide levels as compared to l-dopa or rasagiline, respectively. Furthermore, they also exerted a protective effect against the neurodegenerative histopathological changes induced by PQ.ConclusionsOur findings demonstrated co-administration of COF or CAF, adenosine 2A receptor antagonists, along with l-dopa or rasagiline possesses a new therapeutic strategy for the management of PD neurochemical disturbances and motor behavior impairments through preservation of the brain dopamine and serotonin content, antioxidants level and histological features.

Correlations of blood and brain biochemistry in phenylketonuria: Results from the Pah-enu2 PKU mouse

BackgroundIn phenylketonuria (PKU), treatment monitoring is based on frequent blood phenylalanine (Phe) measurements, as this is the predictor of neurocognitive and behavioural outcome by reflecting brain Phe concentrations and brain biochemical changes. Despite clinical studies describing the relevance of blood Phe to outcome in PKU patients, blood Phe does not explain the variance in neurocognitive and behavioural outcome completely. MethodsIn a PKU mouse model we investigated 1) the relationship between plasma Phe and brain biochemistry (Brain Phe and monoaminergic neurotransmitter concentrations), and 2) whether blood non-Phe Large Neutral Amino Acids (LNAA) would be of additional value to blood Phe concentrations to explain brain biochemistry. To this purpose, we assessed blood amino acid concentrations and brain Phe as well as monoaminergic neurotransmitter levels in in 114 Pah-Enu2 mice on both B6 and BTBR backgrounds using (multiple) linear regression analyses. ResultsPlasma Phe concentrations were strongly correlated to brain Phe concentrations, significantly negatively correlated to brain serotonin and norepinephrine concentrations and only weakly correlated to brain dopamine concentrations. From all blood markers, Phe showed the strongest correlation to brain biochemistry in PKU mice. Including non-Phe LNAA concentrations to the multiple regression model, in addition to plasma Phe, did not help explain brain biochemistry. ConclusionThis study showed that blood Phe is still the best amino acid predictor of brain biochemistry in PKU. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain Phe concentrations, necessitating a search for other additional parameters. Take-home messageBlood Phe is still the best amino acid predictor of brain biochemistry in PKU. Nevertheless, neurocognitive and behavioural outcome cannot fully be explained by blood or brain Phe concentrations, necessitating a search for other additional parameters.

Dietary tryptophan supplementation does not affect growth but increases brain serotonin level and modulates the expression of some liver genes in zebrafish (Danio rerio).

This study aimed at assessing the effects of the dietary tryptophan (Trp) supplementation on growth and feed utilization, brain serotonin content, and expression of selected liver genes (involved in the liver serotonin pathway, protein synthesis degradation, and antioxidant activity) in zebrafish. A growth trial was conducted with zebrafish juveniles fed five experimental isoproteic (40%DM) and isolipidic (8%DM) fishmeal-based diets containing graded levels of Trp: a Trp-non-supplemented diet (diet Trp0, with 0.22% Trp) and four Trp-supplemented diets containing 2-16 times higher Trp content (diets Trp2, Trp4, Trp8, and Trp16 with 0.40, 0.91, 2.02, and 3.34% Trp, respectively). Diets were tested in quadruplicate, with fish being fed twice a day, 6days a week for 6weeks to apparent visual satiation. At the end of the trial, growth performance and feed utilization were assessed, and fish from all experimental groups were sampled for whole-body composition analysis. In addition, fish fed low (Trp0), medium (Trp4), and high (Trp16) Trp diets were also sampled for analysis of brain serotonin content and liver gene expression. Tested tryptophan levels did not influence growth performance nor feed intake. However, values of energy and nitrogen retention as well as body energy content indicate a better feed utilization with diets containing around 0.9% and 2.0% DM Trp. Brain serotonin content increased with increasing dietary tryptophan levels. In addition, regarding liver genes, dietary treatment had a modulatory effect on the expression of Htr1aa and Htr2cl1 genes (encoding for serotonin receptors), TPH1a gene (encoding for tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of serotonin from tryptophan), TOR gene (involved in protein synthesis), and Keap1 gene (involved in antioxidant responses).

Disruption of brain conductivity and permittivity and neurotransmitters induced by citrate-coated silver nanoparticles in male rats.

As one of the most exonerative, competitive, and abundant nanoparticles in curative uses, silver nanoparticles (AgNPs) play a growing important role in developing global neurodegeneration. Herein, we inspected the neurotoxic and histopathological effects of the oral dose of 26.9 nm citrate-coated AgNPs (100 and 1000 mg/kgbw, 28 days) on the brain conductivity and permittivity combined with neurotransmitter assays. While male mice in the control group were given deionized water. In terms of biophysical levels, the brain electric conductivity and relative permittivity were significantly decreased in the 26.9 nm citrate-coated AgNP treated groups versus the controls. Besides, 26.9 nm citrate-coated AgNP treatment resulted in a significant deficiency in the concentrations of brain acetylcholine esterase, dopamine, and serotonin. Total brain contents of silver ion significantly increased in a dose-dependent manner. Further, light and electron microscopy revealed a progressive disruption in the lamellar pattern of the myelinated axons of the nerve fibers, in addition to the accumulation of nanosilver in lysosomes and swollen mitochondria in axoplasm. In conclusion, 26.9 nm citrate-coated AgNPs are capable of gaining access to the brain of mice and causing electric conductivity and relative permittivity damage along with a high degree of cellular toxicity in the brain tissue. Therefore, the present study highlights, for the first time, the adverse effects of the citrate-coated AgNPs to the brain of mice and raises the concern of their probable neurotoxic impacts which is helpful for conclusive interpretation of future behavioral and potential neurodegeneration-based aspects. It would be of interest to investigate citrate-coated AgNPs mediated axonal relevant-signal transduction levels in future studies.

Effects of supplementing different chromium histidinate complexes on glucose and lipid metabolism and related protein expressions in rats fed a high-fat diet

BackgroundThe objective of this study was to investigate the effects of different chromium histidinate (CrHis) complexes added to the diet of rats fed a high-fat diet (HFD) on body weight changes, glucose and lipid metabolism parameters, and changes in biomarkers such as PPAR-γ, IRS-1, GLUTs, and NF-κB proteins. MethodsForty-two Sprague–Dawley rats were divided equally into six groups and fed either a control, an HFD, or an HFD supplemented with either CrHis1, CrHis2, CrHis3, or a combination of the CrHis complexes as CrHisM. ResultsFeeding an HFD to rats increased body weights, HOMA-IR values, fasting serum glucose, insulin, leptin, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and MDA concentrations as well as AST activities, and decreased serum and brain serotonin concentrations compared with rats fed a control diet (P < 0.0001). The levels of the PPAR-γ, IRS-1, and GLUTs in the liver and brain decreased, while NF-κB level increased, with feeding an HFD (P < 0.05). Although all the CrHis supplements reversed the negative effects of feeding an HFD (P < 0.05), the CrHis1 complex was most effective in changing the protein levels, while CrHisM was most effective in influencing certain parameters such as body weight and serum metabolites. ConclusionThe results of the present work suggest that the CrHis1 complex is most potent for alleviating the negative effects of feeding an HFD. The efficacy of CrHisM is likely due to the presence of the CrHis1 complex.

Neonatal Serotonin Depletion Induces Hyperactivity and Anxiolytic-like Sex-Dependent Effects in Adult Rats.

The serotoninergic system plays an important role in the ontogeny of the mammalian central nervous system, and changes in serotonin production during development may lead to permanent changes in brain cytoarchitecture and function. The present study investigated the programming effects of neonatal serotonin depletion on behavior and molecular components of the serotoninergic system in adult male and female rats. Subcutaneous para-chlorophenylalanine (pCPA) administration (100mgkg-1) was performed daily on postnatal days 8-16 to deplete brain serotonin content. During adulthood, elevated plus-maze, open field, social interaction, forced swimming, and food, saline, and sucrose intake tests were performed. Relative expression of serotonin neurotransmission components in several brain areas was determined by qPCR. Additionally, serotonin immunofluorescence and neuropeptide mRNA expression were assessed in dorsal raphe (DRN) and paraventricular (PVN) nuclei, respectively. Rat performance in behavioral tests demonstrated a general increase in locomotor activity and active escape behavior as well as decreased anxiety-like behavior after neonatal brain serotonin depletion. The behavioral programming effects due to neonatal serotonin depletion were more pronounced in females than males. At the gene expression level, the mRNA of Tph1 and Tph2 were lower in DRN while Htr2c was higher in the amygdala of pCPA-treatedmales, while Htr1a, Htr2c, Oxt, Avp, Crh, and Trh were not different in any treatments or sex in PVN. The results indicate that neonatal serotonin depletion has long-term consequences on locomotion and anxiety-like behavior associated with long-lasting molecular changes in the brain serotoninergic system in adult rats.

I. inflexus (Thunb.) Kudo extract improves atopic dermatitis and depressive-like behavior in DfE-induced atopic dermatitis-like disease

BackgroundAtopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease, which is caused by several genetic, immunological, and environmental factors. In addition to skin manifestations, AD is associated with an increased risk of depression and suicidal ideation. Furthermore, this association is underappreciated and therefore insufficiently studied. Hypothesis/PurposeWe investigated the association between AD and depression and the effect of I. inflexus (Thunb.) Kudo extract (IIE) treatment in a Dermatophagoides farinae extract (DfE)-induced mouse model of AD. Study DesignWe evaluated the effects of IIE on depressive behavior in AD mice using four experimental groups: normal (untreated), AD mice (untreated Dfe-induced), IIE-treated (Dfe-induced AD mice), and positive control (tacrolimus-treated Dfe-induced AD mice). MethodsAn AD model was established by the application of 4% sodium dodecyl sulfate to the shaved dorsal neck skin and ears of NC/Nga mice 1 h before application of 100 mg DfE twice per week for 3 weeks. After the first week of DfE application, mice were treated with IIE every day for the remaining 2 weeks. We performed behavioral testing, histology, ELISA, and western blotting to assess depressive-like behavior and neuroinflammatory responses and to measure IgE, histamine, corticosterone, and serotonin levels. ResultsCompared with normal mice, AD mice showed more scratching behavior, increased ear swelling, and higher serum levels of IgE and histamine. AD mice also exhibited evidence of depressive-like behavior in the open-field and sucrose preference tests as well as altered serum corticosterone and brain serotonin concentrations. Histopathological analyses revealed increased infiltration of inflammatory cells and mast cells into the skin and ear tissue and elevated microglia activation and neuroinflammatory response in the brains of AD mice. Topical application of IIE reversed the effects of AD on scratching behavior, ear swelling, open-field locomotion, sucrose preference, and levels of IgE, histamine, corticosterone, serotonin, and inflammatory markers. Moreover, IIE treatment reduced inflammatory cytokine responses in keratinocyte cells. ConclusionIIE is a candidate anti-AD therapy due to its ability to exert neuroprotective and antidepressant effects.

Detection of a High-Turnover Serotonin Circuit in the Mouse Brain Using Mass Spectrometry Imaging.

SummaryMonoamine neurotransmitters are released by specialized neurons regulating behavioral, motor, and cognitive functions. Although the localization of monoaminergic neurons in the brain is well known, the distribution and kinetics of monoamines remain unclear. Here, we generated a murine brain atlas of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels using mass spectrometry imaging (MSI). We found several nuclei rich in both 5-HT and a catecholamine (DA or NE) and identified the paraventricular nucleus of the thalamus (PVT), where 5-HT and NE are co-localized. The analysis of 5-HT fluctuations in response to acute tryptophan depletion and infusion of isotope-labeled tryptophan in vivo revealed a close kinetic association between the raphe nuclei, PVT, and amygdala but not the other nuclei. Our findings imply the existence of a highly dynamic 5-HT-mediated raphe to PVT pathway that likely plays a role in the brain monoamine system.

Citalopram and Tianeptine: Pharmacological Interventions in alcohol withdrawal-induced negative mood states and serotonin insufficiency in Albino Wistar male rats

ABSTRACT The present study aims to investigate the neurochemical and behavioural effects of tianeptine and citalopram to block alcohol withdrawal-induced audiogenic seizures in alcohol withdrawal (AW) rats. Citalopram and tianeptine were administered sub-chronically to block AW-induced audiogenic seizures. Brain regional tryptophan (TRP), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined using high-performance liquid chromatography connected to the fluorimetric detector. Citalopram increased brain TRP concentration in all the regions, however, tianeptine increased brain TRP concentration only in amygdala and hippocampus. Increased brain serotonin concentration was seen by citalopram but not by tianeptine in all the regions. Further, tianeptine was shown to increase 5-HT turnover in all the regions, however, citalopram appeared to increase 5-HT turnover only in the hippocampus. It is concluded that the citalopram and tianeptine behave differently on the intrinsic pathway of serotonin metabolism that appeared to be compensated by the release pattern of serotonin. Further, chronic exposure of serotonergic agents causes restoration and structural reforming of serotonin reuptake mechanism that is desensitized following chronic alcohol exposure. Thus the inclusive approach of the serotonergic system plays an undoubted role in the pharmacological management of AW syndrome.

Low cholesterol is not always good: low cholesterol levels are associated with decreased serotonin and increased aggression in fish.

ABSTRACTThe inverse relationship between serum cholesterol and levels of aggression led to the cholesterol-serotonin hypothesis. According to this hypothesis, low dietary cholesterol intake leads to depressed central serotonergic activity, which is associated with increased aggression. Here we present the hypothesis about the evolutionary origins of low cholesterol and aggressive behavior, investigating the relationship between low levels of plasma cholesterol and aggressive behavior in fish. We used Nile tilapia (Oreochromis niloticus), a species of aggressive fish with a clear dominant subordinate relation, as an experimental model. The fish were treated with statin, a cholesterol-lowering drug. Aggressive behavior, brain serotonin (5-HT) concentrations, 5-hydroxyindoleacetic acid (5-HIAA, the major 5-HT metabolite) and plasma cholesterol were analyzed after chronic administration of statin. Our results show that fish treated with statin exhibited reduced plasma cholesterol, reduced telencephalic indexes of 5-HIAA/5-HT and increased aggressive behavior compared to control fish. These results indicate that changes in plasma cholesterol may affect neurochemical processes underlying aggressive behavior in fish, suggesting an evolutionary mechanism conserved among vertebrates. Such mechanisms may be important for the control of aggression in many vertebrate species, not just mammals, as has been demonstrated so far.

Consumption of plantain suppresses pain and enhances social behavior in mice

PurposePlantain (Musa paradisiaca), a staple food source for many people especially in the tropics, contains the neurotransmitter, serotonin which has analgesic and antidepressant effects. Therefore, this study aims to investigate the effects of chronic consumption of plantain diet on pain perception and social behavior in mice.Design/methodology/approachIn the first set of experiments, three groups of mice were either fed rodent chow (control) or 50 or 100 per cent plantain diet, while in a second set of experiments, another three groups of mice were fed either rodent chow (control) or 100 per cent plantain or plantain + ritanserin (serotonin antagonist) for 30 days. Response to pain stimuli was studied by hot plate and formalin tests. Also, the ability of the mice to fluff up suitable beds to build nestle from nesting material was used as an index for social behavior. Serotonin concentration in mice brain was measured using high performance liquid chromatography.FindingsThe results showed that plantain diet-fed mice consumed less food but gained more body weight than control mice. Pain perception was significantly reduced in the plantain diet-fed mice compared to the control. Social behavior was enhanced in the plantain diet-fed mice when compared to control (p < 0.05). There was significant increase in serotonin concentration in the brains of 100 per cent diet-fed mice. Administration of serotonin blocker, ritanserin reversed the effects observed in pain and social behavior tests.Originality/valueChronic consumption of plantain diet increases serotonin concentration in the brain, suppresses spontaneous perception of pain and improves social behavior in mice. These actions may involve serotonergic pathway.

Tetrahydrobiopterin treatment reduces brain L-Phe but only partially improves serotonin in hyperphenylalaninemic ENU1/2 mice.

Hyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH4) treatment in Pahenu1/enu2 (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type. We found that brain L-tyrosine, L-tryptophan, BH4 cofactor and catecholamine concentrations, and brain tyrosine hydroxylase (TH) activity were normal in these mice but that brain serotonin, 5-hydroxyindolacetic acid (5HIAA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) content, and brain TH protein, as well as tryptophan hydroxylase type 2 (TPH2) protein levels and activity were reduced in comparison to wild-type mice. Parenteral L-Phe loading conditions did not lead to significant changes in brain neurometabolite concentrations. Remarkably, enteral BH4 treatment, which normalized brain L-Phe levels in ENU1/2 mice, lead to only partial recovery of brain serotonin and 5HIAA concentrations. Furthermore, indirect evidence indicated that the GTP cyclohydrolase I (GTPCH) feedback regulatory protein (GFRP) complex may be a sensor for brain L-Phe elevation to ameliorate the toxic effects of HPA. We conclude that BH4 treatment of HPA toward systemic L-Phe lowering reverses elevated brain L-Phe content but the recovery of TPH2 protein and activity as well as serotonin levels is suboptimal, indicating that patients with mild HPA and mood problems (depression or anxiety) treated with the current diet may benefit from supplementation with BH4 and 5-OH-tryptophan.