Decreased Serotonin Levels Research Articles

Humoral serotonin and neuropsychological status of patients with dizziness

Dizziness is often accompanied by affective disorders such as anxiety and depression, in the occurrence of which the role of the serotonergic system is discussed.Objective: to investigate the serotonin content in blood serum and neuropsychological status in patients with vestibular and non-vestibular dizziness.Material and methods. The study included 97 patients. Two observation groups were formed according to the type of dizziness complaints. The first group (n=47) comprised patients with vestibular (systemic) dizziness against a background of peripheral vestibulopathy, the second group (n=35) comprised patients with non-vestibular (non-systemic) dizziness with a diagnosis of probable persistent postural-perceptual dizziness (PPPD). The control group (n=15) consisted of patients without complaints of dizziness. Neurological and otoneurological status, psychoemotional parameters (level of anxiety and depression) and cognitive functions were analyzed, and the quantitative level of serotonin in blood serum was determined by enzyme immunoassay.Results. The study revealed a significant decrease in the serum serotonin levels in vestibular and non-vestibular dizziness; a lower serotonin level was found in non-vestibular dizziness (p<0.05). The presence of affective disorders did not correlate with a decrease in serotonin levels in vestibular dizziness against a background of peripheral vestibulopathy. It is assumed that a decrease in serotonin content plays a role in pathogenesis of vestibular dizziness on the background of peripheral part of vestibular system involvement.Conclusion. We demonstrated possibility of using the level of serotonin in peripheral blood as an objective laboratory marker of vestibular and non-vestibular dizziness in general clinical medical practice.

Kefir recovered depressive-like behaviour in CantonS lineage of Drosophila melanogaster exposed to chronic unpredictable mild stress protocol.

Chronic unpredictable mild stress (CUMS) is a widely accepted method for inducing depressive-like states in animal models. We decided to explore the effects of CUMS on the CantonS lineage of Drosophila melanogaster, which differs from the OregonR lineage in various ways. Additionally, we wanted to investigate the potential benefits of kefir in treating these chronically stressed flies, as previous research has shown promising results in using kefir components for depression treatment. To begin, we exposed male CantonS flies to a 10-day CUMS protocol and compared them to non-stressed flies. Within the stressed group, we had two subgroups: one treated with kefir (CUMS+ Kefir group) and the other treated with sertraline (positive control). We then analysed various factors including serotonin levels, brain structure, markers of oxidative damage in lipids and proteins, and behavioural manifestations such as sociability, locomotor function, and anhedonic-like behaviour. Our results showed that flies exposed to CUMS experienced a decrease in serotonin levels without any signs of degeneration. They also exhibited reduced sociability, increased motor agitation, and decreased sucrose consumption, which are all indicative of stress-induced depressive-like behaviour. However, treatment with sertraline partially reversed these effects. Interestingly, treatment with kefir not only restored serotonin levels but also improved sociability and anhedonic-like behaviours. Additionally, flies in the CUMS+ Kefir group had a longer lifespan compared to their untreated counterparts. These findings suggest that kefir has multiple advantageous effects on flies subjected to the 10-day CUMS protocol. In conclusion, our study demonstrates that the CantonS lineage of D. melanogaster displays depressive-like manifestations after exposure to CUMS. Furthermore, kefir emerges as a powerful nutritional tool capable of reversing these effects and promoting beneficial outcomes in chronically stressed flies.

Telotristat ethyl, a tryptophan hydroxylase inhibitor, enhances antitumor efficacy of standard chemotherapy in preclinical cholangiocarcinoma models.

Cholangiocarcinoma (CCA), an aggressive biliary tract cancer, carries a grim prognosis with a 5-year survival rate of 5%-15%. Standard chemotherapy regimens for CCA, gemcitabine plus cisplatin (GemCis) or its recently approved combination with durvalumab demonstrate dismal clinical activity, yielding a median survival of 12-14 months. Increased serotonin accumulation and secretion have been implicated in the oncogenic activity of CCA. This study investigated the therapeutic efficacy of telotristat ethyl (TE), a tryptophan hydroxylase inhibitor blocking serotonin biosynthesis, in combination with standard chemotherapies in preclinical CCA models. Nab-paclitaxel (NPT) significantly enhanced animal survival (60%), surpassing the marginal effects of TE (11%) or GemCis (9%) in peritoneal dissemination xenografts. Combining TE with GemCis (26%) or NPT (68%) further increased survival rates. In intrahepatic (iCCA), distal (dCCA) and perihilar (pCCA) subcutaneous xenografts, TE exhibited substantial tumour growth inhibition (41%-53%) compared to NPT (56%-69%) or GemCis (37%-58%). The combination of TE with chemotherapy demonstrated enhanced tumour growth inhibition in all three cell-derived xenografts (67%-90%). PDX studies revealed TE's marked inhibition of tumour growth (40%-73%) compared to GemCis (80%-86%) or NPT (57%-76%). Again, combining TE with chemotherapy exhibited an additive effect. Tumour cell proliferation reduction aligned with tumour growth inhibition in all CDX and PDX tumours. Furthermore, TE treatment consistently decreased serotonin levels in all tumours under all therapeutic conditions. This investigation decisively demonstrated the antitumor efficacy of TE across a spectrum of CCA preclinical models, suggesting that combination therapies involving TE, particularly for patients exhibiting serotonin overexpression, hold the promise of improving clinical CCA therapy.

Pineapple (Ananas comosus) Ameliorates Depressant-like Behaviors in Rats Induced by Lipopolysaccharide

Background: Lipopolysaccharide (LPS) injection can lead to depression and mood disorders by reducing tryptophan availability through increased activity of the enzyme indoleamine 2,3-dioxygenase. Tryptophan, sourced from fruits such as pineapple (Ananas cosmosus), is vital for the body, especially the serotonergic system. Aim: This study aims to assess how pineapple pulp (PP) counters LPS-induced depressive behaviors in male Wistar rats. Methods: The experiment involved force-feeding PP for 28 days before LPS injection (0.5 mg/kg intraperitoneal [i.p.]) in 30 male Wistar rats, divided into five groups. Groups I (normal) and II (LPS control) received 15 ml aquadest/kg/day. Test Groups III, IV, and V were given varied doses of PP; low dose (3.75 ml/kg/day), medium dose (7.5 ml/kg/day), and high dose (15 ml/kg/day). At the study’s end, rats underwent the open field test (OFT) and the tail suspension test (TST). In addition, blood and brain samples were analyzed for neuroendocrine markers related to depression. Results: LPS triggers depressive symptoms, as evidenced by increased immobility time in the TST and altered behaviors indicative of anxiety in the OFT, especially in groups not receiving PP. This is followed by decreased serotonin levels in both plasma and brain when compared to groups given PP. In addition, higher corticosterone levels were observed in the LPS group than in the PP-treated group. Administering PP at 7.5 ml/kg/day for 28 days can alleviate the depressive effects induced by LPS injection. Conclusion: PP may have antidepressant properties, potentially by mitigating behaviors leading to depressive symptoms.

Poor Decision Making and Sociability Impairment Following Central Serotonin Reduction in Inducible TPH2-Knockdown Rats.

Serotonin is an essential neuromodulator for mental health and animals' socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here, we investigated how a mild and acute decrease in brain serotonin would affect rats' cognitive abilities. Using a novel rat model of inducible serotonin depletion via the genetic knockdown of tryptophan hydroxylase 2 (TPH2), we achieved a 20% decrease in serotonin levels in the hypothalamus after three weeks of non-invasive oral doxycycline administration. Decision making, cognitive flexibility, and social recognition memory were tested in low-serotonin (Tph2-kd) and control rats. Our results showed that the Tph2-kd rats were more prone to choose disadvantageously in the long term (poor decision making) in the Rat Gambling Task and that only the low-serotonin poor decision makers were more sensitive to probabilistic discounting and had poorer social recognition memory than other low-serotonin and control individuals. Flexibility was unaffected by the acute brain serotonin reduction. Poor social recognition memory was the most central characteristic of the behavioral network of low-serotonin poor decision makers, suggesting a key role of social recognition in the expression of their profile. The acute decrease in brain serotonin appeared to specifically amplify the cognitive impairments of the subgroup of individuals also identified as poor decision makers in the population. This study highlights the great opportunity the Tph2-kd rat model offers to study inter-individual susceptibilities to develop cognitive impairment following mild variations of brain serotonin in otherwise healthy individuals. These transgenic and differential approaches together could be critical for the identification of translational markers and vulnerabilities in the development of mental disorders.

The effect of 4 week-long swimming exercise intervention on increased serotonin levels in male mice (Mus musculus)

Abstract Being overweight can be caused by an imbalance between calorie intake and energy expenditure over a long period, and the brain plays an important role in controlling overeating responses. Serotonin is a neurotransmitter involved in regulating food intake and weight. Being overweight is associated with decreased serotonin levels. Decreased serotonin levels have an impact on increased health disorders and depression. The study aimed to analyse the effect of 4 week-long swimming exercise intervention on increased serotonin levels in male mice (Mus musculus). A total of 18 male mice (20-40 g), aged eight weeks with (Lee index (LI) ≥0.3) randomly assigned to three groups: COG (n = 6; control group without intervention), MEG (n = 6; moderate-intensity morning exercise group), and AEG (n = 6; moderate-intensity afternoon exercise group). Morning and afternoon exercise was carried out with a load of 5% of the total body weight of mice. Four weeks of exercise with a frequency of three times a week and were performed for 70% of the maximum duration per session. Blood collection was done 2 × 24 h after the last intervention. Measurement of serum serotonin levels using ELISA. Data analysis techniques using the one-way ANOVA test with SPSS version 17 software. The average levels of serum serotonin of COG were (56.29 ± 3.59 ng/ml), MEG (86.21 ± 18.44 ng/ml), AEG (82.73 ± 25.15 ng/ml), and (). The results of this study show that moderate-intensity exercises in the morning and afternoon increase serum serotonin levels in male mice. Therefore, moderate-intensity morning and afternoon swimming exercises can be used in controlling and inhibiting the over-eating response mediated by the serotonin.

An AI-powered patient triage platform for future viral outbreaks using COVID-19 as a disease model

Over the last century, outbreaks and pandemics have occurred with disturbing regularity, necessitating advance preparation and large-scale, coordinated response. Here, we developed a machine learning predictive model of disease severity and length of hospitalization for COVID-19, which can be utilized as a platform for future unknown viral outbreaks. We combined untargeted metabolomics on plasma data obtained from COVID-19 patients (n = 111) during hospitalization and healthy controls (n = 342), clinical and comorbidity data (n = 508) to build this patient triage platform, which consists of three parts: (i) the clinical decision tree, which amongst other biomarkers showed that patients with increased eosinophils have worse disease prognosis and can serve as a new potential biomarker with high accuracy (AUC = 0.974), (ii) the estimation of patient hospitalization length with ± 5 days error (R2 = 0.9765) and (iii) the prediction of the disease severity and the need of patient transfer to the intensive care unit. We report a significant decrease in serotonin levels in patients who needed positive airway pressure oxygen and/or were intubated. Furthermore, 5-hydroxy tryptophan, allantoin, and glucuronic acid metabolites were increased in COVID-19 patients and collectively they can serve as biomarkers to predict disease progression. The ability to quickly identify which patients will develop life-threatening illness would allow the efficient allocation of medical resources and implementation of the most effective medical interventions. We would advocate that the same approach could be utilized in future viral outbreaks to help hospitals triage patients more effectively and improve patient outcomes while optimizing healthcare resources.

The Effect of Forced Exercise on Striatal and Serum Serotonin Levels in a Parkinson’s Mouse Model

Objective: The general treatment approach for Parkinson's disease (PD) is L-dopa administration. While L-dopa only relieves dopaminergic deficiency, it has no effect on the serotonergic system, which is thought to be impaired in the disease. The limitations of current treatment methods have made it necessary to discover new approaches to the treatment of the disease. Studies conducted in recent years report that different types of exercises applied lead to improvement in the symptoms of PD. Exercising decreases serotonin levels and increases dopamine levels. However, the effect of exercise on serotonin levels together with dopamine in PD and its effect on non-motor symptoms such as anxiety and depression are unknown.
 Methods: PD is created using MPTP. The exercise groups were given challenging treadmill exercises for 6 weeks. Serotonin and dopamine levels were measured in the striatum and serum. Parkinson's symptoms were examined with pole test and behavioral tests.
 Results: Exercise significantly reduced bradykinesia, increased motor activity, and decreased anxiety behaviors in the exercise groups. While exercise increased striatal dopamine levels in all exercise groups, there was no difference in striatal serotonin levels. However, the serotonin serum level was decreased in the PD model group. While treadmill exercise increased striatal dopamine levels in the Parkinson's mouse model, it did not cause any change in striatal serotonin levels. However, the decrease in serum serotonin level was determined only in the MPTP group.
 Conclusion: The fact that the decrease in serotonin level was only in the disease group and the lower level of anxiety observed in behavioral experiments suggested that regular treadmill exercise was the reason. However, this improvement was not observed in cases where the anxiety level was very high.

Experimental Increase and Decrease in Serotonin Level of Females Regulate the Developmental Trajectory of Their Offspring in Fish with Embryonic Diapause

Experimental Increase and Decrease in Serotonin Level of Females Regulate the Developmental Trajectory of Their Offspring in Fish with Embryonic Diapause

Distinct serotonergic pathways to the amygdala underlie separate behavioral features of anxiety.

Anxiety-like behaviors in mice include social avoidance and avoidance of bright spaces. Whether these features are distinctly regulated is unclear. We demonstrate that in mice, social and anxiogenic stimuli, respectively, increase and decrease serotonin (5-HT) levels in basal amygdala (BA). In dorsal raphe nucleus (DRN), 5-HT∩vGluT3 neurons projecting to BA parvalbumin (DRN5-HT∩vGluT3-BAPV) and pyramidal (DRN5-HT∩vGluT3-BAPyr) neurons have distinct intrinsic properties and gene expression and respond to anxiogenic and social stimuli, respectively. Activation of DRN5-HT∩vGluT3→BAPV inhibits 5-HT release via GABAB receptors on serotonergic terminals in BA, inducing social avoidance and avoidance of bright spaces. Activation of DRN5-HT∩vGluT3→BA neurons inhibits two subsets of BAPyr neurons via 5-HT1A receptors (HTR1A) and 5-HT1B receptors (HTR1B). Pharmacological inhibition of HTR1A and HTR1B in BA induces avoidance of bright spaces and social avoidance, respectively. These findings highlight the functional significance of heterogenic inputs from DRN to BA subpopulations in the regulation of separate anxiety-related behaviors.

An In Vivo Definition of Brain Histamine Dynamics Reveals Critical Neuromodulatory Roles for This Elusive Messenger.

Histamine is well known for mediating peripheral inflammation; however, this amine is also found in high concentrations in the brain where its roles are much less known. In vivo chemical dynamics are difficult to measure, thus fundamental aspects of histamine's neurochemistry remain undefined. In this work, we undertake the first in-depth characterization of real time in vivo histamine dynamics using fast electrochemical tools. We find that histamine release is sensitive to pharmacological manipulation at the level of synthesis, packaging, autoreceptors and metabolism. We find two breakthrough aspects of histamine modulation. First, differences in H3 receptor regulation between sexes show that histamine release in female mice is much more tightly regulated than in male mice under H3 or inflammatory drug challenge. We hypothesize that this finding may contribute to hormone-mediated neuroprotection mechanisms in female mice. Second, a high dose of a commonly available antihistamine, the H1 receptor inverse agonist diphenhydramine, rapidly decreases serotonin levels. This finding highlights the sheer significance of pharmaceuticals on neuromodulation. Our study opens the path to better understanding and treating histamine related disorders of the brain (such as neuroinflammation), emphasizing that sex and modulation (of serotonin) are critical factors to consider when studying/designing new histamine targeting therapeutics.

Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease

RationaleThe pharmacological effects of antidepressants in modulating noradrenergic transmission as compared to serotonergic transmission in a rat model of Parkinson’s disease under chronic L-DOPA therapy are insufficiently explored.ObjectivesThe aim of the present study was to investigate the effect of the tricyclic antidepressant desipramine administered chronically alone or jointly with L-DOPA, on motor behavior and monoamine metabolism in selected brain structures of rats with the unilateral 6-OHDA lesion.MethodsThe antiparkinsonian activities of L-DOPA and desipramine were assessed behaviorally using a rotation test and biochemically based on changes in the tissue concentrations of noradrenaline, dopamine and serotonin and their metabolites, evaluated separately for the ipsi- and contralateral motor (striatum, substantia nigra) and limbic (prefrontal cortex, hippocampus) structures of rat brain by HPLC method.ResultsDesipramine administered alone did not induce rotational behavior, but in combination with L-DOPA, it increased the number of contralateral rotations more strongly than L-DOPA alone. Both L-DOPA and desipramine + L-DOPA significantly increased DA levels in the ipsilateral striatum, substantia nigra, prefrontal cortex and the ipsi- and contralateral hippocampus. The combined treatment also significantly increased noradrenaline content in the ipsi- and contralateral striatum, while L-DOPA alone decreased serotonin level on both sides of the hippocampus.ConclusionsThe performed analysis of the level of monoamines and their metabolites in the selected brain structures suggests that co-modulation of noradrenergic and dopaminergic transmission in Parkinson’s disease by the combined therapy with desipramine + L-DOPA may have some positive implications for motor and psychiatric functions but further research is needed to exclude potential negative effects.

Luteolin reduces fear, anxiety, and depression in rats with post-traumatic stress disorder

ABSTRACT Exposure to severe stress can lead to the development of neuropsychiatric disorders, including post-traumatic stress disorder (PTSD). The cause of PTSD is dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and an imbalance of monoamines. Fruits and vegetables contain large amounts of luteolin (LU; 3′,4′,5,7-tetrahydroxylflavone), which has various pharmacological activities such as anti-inflammatory, antioxidant, and anti-allergic effects. We investigated the effects of LU on fear, depression, and anxiety following monoamine imbalance and hyperactivation of the HPA axis in rats exposed to single prolonged stress (SPS). Male rats were dosed with LU (10 and 20 mg/kg) once daily for 14 days after exposure to SPS. Administration of LU reduced fear freezing responses to extinction recall and depression- and anxiety-like behaviors, and suppressed increases in plasma corticosterone and adrenocorticotropic hormone levels. Also, administration of LU restored the increased norepinephrine and decreased serotonin levels in the structures within the fear circuit, medial prefrontal cortex, and hippocampus. Our results showed that administration of LU improved freezing behavior according in a situation-dependent manner, and showed anti-depressant and anxiolytic effects. Thus, LU may be a useful therapeutic agent to prevent traumatic stress such as PTSD.

THE VALUES AND THE DIFFERENCES OF THE SEROTONIN LEVELS IN SERUM AND BRAIN TISSUE IN AN INDUCED DIABETIC NEPHROPATHY WHITE LABORATORY RAT UNDER THE IMPACT OF PERINDOPRIL AND CANDESARTAN

Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system (RAAS) and plays a role in the pathophysiology of hypertension, heart failure, renal failure and other cardiovascular disorders. RAAS is activated in diabetic nephropathy (DN) and leads to more renal damage. Angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers suppress this (ARBs). A large body of evidence demonstrates that, in addition to its typical activity as a hormone, Ang II is a neuropeptide produced by the central nervous system (CNS) that acts as a regulator of neurotransmission and nerve cell excitability. Peripheral serotonin is an endocrine component that promotes energy storage efficiency. Serotonin also enters the bloodstream and interacts with multiple organs, priming the body for energy storage by promoting insulin secretion and de novo lipogenesis in the liver and white adipose tissue. However, the actions of serotonin extend beyond neuronal communication in the CNS and enteric nervous system (ENS) to peripheral tissues. Serotonin mediates numerous nonneuronal processes such as bladder function, respiratory drive, hemostasis, vascular tone, immune function, and intestinal inflammation . The goal of this study is to see how the ACE inhibitor perindopril and the ARB AT1 candesartan, taken singly and in combination (double blockade), affect serotonin levels in the serum and brain tissue of Wistar rats with DN caused by streptozotocin (STZ). The levels of serotonin in the serum and brain of four experimental groups of animals were measured using an enzyme-linked immunosorbent assay (ELISA): a control group with DN, a group with DN treated with perindopril, a group with DN treated with candesartan, and a DN group treated with a combination of perindopril and candesartan. Perindopril (6 mg/Kg/day), candesartan (5 mg/Kg/day), and dual therapy with perindopril (3 mg/Kg/day) and candesartan (2,5 mg/Kg/day) were given orally every day for eight weeks, beginning four weeks after STZ was given, whereas the control group received just water. The rats were slaughtered at the end of the therapy so that the serum and brain tissue could be used to test serotonin levels. The results showed that blocking the renin-angiotensin system (RAS) with perindopril, candesartan, or their combination considerably decreased serotonin levels in the serum but dramatically elevated serotonin levels in the brain tissue in all groups.

Psikoneuroimunologi Depresi pada Polycystic Ovary Syndrome (PCOS)

<p><strong><em>Introduction</em></strong><em>: Polycystic ovary syndrome (PCOS) is heterogeneous, complex endocrine disorder with unknown etiology, affecting 4%−18% of reproductive age women and associated with reproductive, metabolic and psychological dysfunction. Along with physical disorders, many mental disorders are also associated with PCOS, about 40% of women with PCOS have depression. This literature review aims to explore how PCOS can lead to depression in term of psychoneuroimmunology aspects.</em></p><p><strong><em>Method</em></strong><em>: Literature review was conducted through search engine from Google Scholar and Clinical Key with keywords “Polycystic ovary syndrome”, “depression”, “psychoneuroimmunology”, “distress”, and “inflammation” from 2015-2020.</em></p><p><strong><em>Result</em></strong><em>: The important role of the HPG axis in the pathophysiology of mood disorder has concluded that high comorbidity between depression and PCOS are caused by hyperandrogenism and insulin resistance mediated by low grade chronic inflammation. The activation of HPA by stress exerts an inhibitory effect on the female reproductive system. CRH can inhibit GnRH secretion from the hypothalamus. The anti-reproductive action of CRH in the ovaries of women with high psychosocial stress lead to early ovarian failure. In addition, the pathophysiology of depression and mental stress in PCOS is associated with various changes including high activity of pro-inflammation markers and the body's immune system during stress, it has also been linked to increased cortisol levels, increased sympathetic activity and decreased serotonin levels in the central nervous system.</em></p><p><strong><em>Result</em></strong><em>: There’s close relationship between PCOS and depression in terms of psychoneuroimmunology aspects, by HPG axis role. Comprehensive management of depression is improving outcome strategy in women with PCOS by involving CLP.</em></p><p><strong><em>Keywords</em></strong><em>: <strong>Polycystic ovary syndrome (PCOS), Depression, Psychoneuroimmunology, HPG axis</strong></em></p>

Involvement of serotonergic neurotransmission in the antidepressant-like effect elicited by cholecalciferol in the chronic unpredictable stress model in mice.

Cholecalciferol deficiency has been associated with stress-related psychiatric disorders, particularly depression. Therefore, the present study investigated the antidepressant-like effect of cholecalciferol in female mice and the possible role of the serotonergic system in this response. The ability of cholecalciferol to elicit an antidepressant-like effect and to modulate serotonin levels in the hippocampus and prefrontal cortex of mice subjected to chronic unpredictable stress (CUS) was also investigated. The administration of cholecalciferol (2.5, 7.5, and 25µg/kg, p.o.) for 7days, similar to fluoxetine (10mg/kg, p.o., serotonin reuptake inhibitor), reduced the immobility time in the tail suspension test, without altering the locomotor performance in the open-field test. Moreover, the administration of p-chlorophenylalanine methyl ester (PCPA - 100mg/kg, i.p., for 4days, a selective inhibitor of tryptophan hydroxylase, involved in the serotonin synthesis) abolished the antidepressant-like effect of cholecalciferol and fluoxetine in the tail suspension test, demonstrating the involvement of serotonergic system. Additionally, CUS protocol (21days) induced depressive-like behavior in the tail suspension test and decreased serotonin levels in the prefrontal cortex and hippocampus of mice. Conversely, the administration of cholecalciferol and fluoxetine in the last 7days of CUS protocol completely abolished the stress-induced depressive-like phenotype. Cholecalciferol was also effective to abrogate CUS-induced reduction on serotonin levels in the prefrontal cortex, but not in the hippocampus. Our results indicate that cholecalciferol has an antidepressant-like effect in mice by modulating the serotonergic system and support the assumption that cholecalciferol may have beneficial effects for the management of depression.

Postnatal depletion of serotonin affects the morphology of neurons and the function of the hippocampus in male rats.

Serotonin (5-HT) is an essential neurotransmitter for the refined organization of the cerebral cortex. Studies have suggested that altered serotonin signaling contributes to cognitive impairment and psychiatric disorders. However, the exact role of this neurotransmitter on the development of hippocampal neurons is not recognized. Here we aimed to examine the effects of the para-chlorophenylalanine (PCPA; 100 mg/kg/daily, s.c. during the postnatal days 10-20), a reversible inhibitor of 5-HT synthesis, on the serotonin level of the hippocampal and prefrontal cortex. We also focused on the morphology of the neurons in the hippocampus and spatial learning and memory. Our results indicated that the administration of PCPA led to a decrease in serotonin levels in the hippocampus and prefrontal cortex. Postnatal serotonin depletion also induced subtle alterations in the neuronal populations of the hippocampus and impaired spatial memory in the adulthood period of life. We found that critical developmental periods of serotonin depletion caused degeneration and swelling of neurons as well as significant neuronal loss in the hippocampal CA1, CA3, and dentate gyrus (DG) areas. Thus, serotonin, a strikingly important neurotransmitter, can affect neuronal morphology, development, and hippocampal-dependent memory.

Evaluation of the antidepressant-like activity of the aqueous extract of Crataegus aronia

Background: Crataegus aronia L. Syn: Azarolus (C. aronia) is a hawthorn species and a perennial bush native to Mediterranean regions. It is recognized for its high polyphenol content and potent antioxidant effects. Research was conducted to test the antidepressant activities of an aqueous extract of C. aronia in a chronic, unpredictable, mild stress-induced rat model. Materials and Methods: Thirty-two adult Wistar male rats were divided into four groups: A control group (no stress and no treatment), stress-model group (stress and no treatment), fluoxetine-treated stress group (stress and fluoxetine treatment), and C. aronia-treated stress group (stress and C. aronia treatment). Urine samples were collected at 0, 21, 36, and 51 days. Enzyme-linked immunosorbent assay kits were used to assess serotonin, norepinephrine (NE), and dopamine (DA) levels. Results: There was a decrease in serotonin levels 3 weeks after stress exposure, but urinary NE and DA levels increased. C. aronia significantly (P < 0.001) reversed the depressive-like symptoms in the rats according to the increased urinary levels of serotonin. Moreover, C. aronia also reduced urinary levels of urinary NE and DA. The neuromodulatory effects of C. aronia were comparable to that of fluoxetine. Conclusion: With its active ingredients of anthocyanins and procyanidins, C. aronia exhibits significant antidepressant-like activity in validated stressed rats, which may be related to its neuromodulatory effects on central monoamines.

Premenstrual Syndrome Factors in Reproductive Women 18 – 40 Years Old

Premenstrual syndrome (PMS) is a collection of symptoms in reproductive women that appear on the 7-14 days before menstruation, such as physical, psychological, and behavioral disorders. Symptoms that often occur include excessive anxiety, irritability, breast pain, increased or decreased appetite, nausea, vomiting, acne, lumbago and back pain which can reduce productivity. Some experts say that PMS occur due to decreased serotonin levels caused by low physical activity, less or excess BMI, and hypertension. This research aims to analyze the relationship between PMS with physical activity, BMI, and hypertension in women 18-40 years old. This research was an observational analytic study with a cross sectional approach. The total sample was 54 reproductive women in Tuban District according to the inclusion criteria and using purposive sampling. Chi square statistical test was used to determine the significant level of data obtained level of significant α=0,05. After the chi square test was carried out, it was obtained physical activity with ρ = 0,012, BMI with ρ = 0,002, and hypertension with ρ = 0,003. This means there are relationship between physical activity, BMI, and hypertension with PMS. The conclusion is habits in proper and routine physical activity, normal BMI, and no history of hypertension can reduce the PMS complaints.

Impact of chronic sub-lethal methylparaben exposure on cardiac hypoxia and alterations in neuroendocrine factors in zebrafish model.

Endocrine-disrupting chemicals have been shown to cause toxicity in different systems of the body including the endocrine, cardiovascular and nervous systems. This study aims to analyze the adverse effects of Methylparaben (MP) on cardiac functions, neurodevelopment, and behavior of zebrafish. Adult male and female zebrafish were exposed to MP for 30 days to study the toxicity effects. Zebrafish were grouped into control, solvent control, 1/10th (110 ppb), 1/100th, and 1/1000th (1 ppb) lethal concentration 50 of MP. Neurobehavioral assays, acetylcholinesterase (AChE) activity, serotonin levels, and expression of genes-Hypoxia-inducible factor 1 alpha, Neurotrophic Receptor Tyrosine Kinase, Paired box protein Pax-6, and tnnt2 were investigated in zebrafish. Results of the study showed more anxiety-like behavior in MP-treated female zebrafish when compared to males on chronic exposure. There was a dose-dependent reduction of AChE activity in both male and female zebrafish. Female zebrafish showed a dose-dependent increase in serotonin level on MP exposure while male zebrafish showed a dose-independent decrease in serotonin level. On MP exposure, there was also a dose-dependent dysregulation in the expression of cardiac hypoxia and neuronal differentiation-related genes in female zebrafish while a dose-independent change was observed in male zebrafish. Chronic MP exposure affects cardiac functions, neuronal functions, and behavior of zebrafish by exhibiting changes in AChE activity, serotonin levels, and altering the expression of genes related to cardiac hypoxia and neuronal differentiation even at sub-lethal doses.