Brain Dopamine Levels Research Articles

Changes in neurotransmitter levels, brain structural characteristics, and their correlation with PANSS scores in patients with first-episode schizophrenia.

In patients with schizophrenia, the brain structure and neurotransmitter levels change, which may be related to the occurrence and progression of this disease. To explore the relationships between changes in neurotransmitters, brain structural characteristics, and the scores of the Positive and Negative Symptom Scale (PANSS) in patients with first-episode schizophrenia. The case group comprised 97 patients with schizophrenia, who were evaluated using the Canadian Neurological Scale and confirmed by laboratory tests at Ningbo Mental Hospital from January 2020 to July 2022. The control group comprised 100 healthy participants. For all participants, brain structural characteristics were explored by measuring brain dopamine (DA), glutamic acid (Glu), and gamma-aminobutyric acid (GABA) levels, with magnetic resonance imaging. The case group was divided into negative and positive symptom subgroups using PANSS scores for hierarchical analysis. Linear correlation analysis was used to analyze the correlations between neurotransmitters, brain structural characteristics, and PANSS scores. Patients in the case group had higher levels of DA and lower levels of Glu and GABA, greater vertical and horizontal distances between the corpus callosum and the inferior part of the fornix and larger ventricle area than patients in the control group (P < 0.05). Patients with positive schizophrenia symptoms had significantly higher levels of DA, Glu, and GABA than those with negative symptoms (P < 0.05). In patients with positive schizophrenia symptoms, PANSS score was significantly positively correlated with DA, vertical and horizontal distances between the corpus callosum and the infrafornix, and ventricular area, and was significantly negatively correlated with Glu and GABA (P < 0.05). In patients with negative schizophrenia symptoms, PANSS score was significantly positively correlated with DA, vertical distance between the corpus callosum and the infrafornix, horizontal distance between the corpus callosum and the infrafornix, and ventricular area, and was significantly negatively correlated with Glu and GABA (P < 0.05). In patients with first-episode schizophrenia, DA levels increased, Glu and GABA levels decreased, the thickness of the corpus callosum increased, and these variables were correlated with PANSS scores.

Piperine improves levodopa availability in the 6-OHDA-lesioned rat model of Parkinson's disease by suppressing gut bacterial tyrosine decarboxylase.

Tyrosine decarboxylase (TDC) presented in the gut-associated strain Enterococcus faecalis can convert levodopa (L-dopa) into dopamine (DA), and its increased abundance would potentially minimize the availability and efficacy of L-dopa. However, the known human decarboxylase inhibitors are ineffective in this bacteria-mediated conversion. This study aims to investigate the inhibition of piperine (PIP) on L-dopa bacterial metabolism and evaluates the synergistic effect of PIP combined with L-dopa on Parkinson's disease (PD). Metagenomics sequencing was adopted to determine the regulation of PIP on rat intestinal microbiota structure, especially on the relative abundance of E. faecalis. Then, the inhibitory effects of PIP on L-dopa conversion and TDC expression of E. faecalis were tested in vitro. We examined the synergetic effect of the combination of L-dopa and PIP on 6-hydroxydopamine (6-OHDA)-lesioned rats and tested the regulations of L-dopa bioavailability and brain DA level by pharmacokinetics study and MALDI-MS imaging. Finally, we evaluated the microbiota-dependent improvement effect of PIP on L-dopa availability using pseudo-germ-free and E. faecalis-transplanted rats. We found that PIP combined with L-dopa could better ameliorate the move disorders of 6-OHDA-lesioned rats by remarkably improving L-dopa availability and brain DA level than L-dopa alone, which was associated with the effect of PIP on suppressing the bacterial decarboxylation of L-dopa via effectively downregulating the abnormal high abundances of E. faecalis and TDC in 6-OHDA-lesioned rats. Oral administration of L-dopa combined with PIP can improve L-dopa availability and brain DA level in 6-OHDA-lesioned rats by suppressing intestinal bacterial TDC.

Obesity Impairs Cognitive Function with No Effects on Anxiety-like Behaviour in Zebrafish.

Over the last decade, the zebrafish has emerged as an important model organism for behavioural studies and neurological disorders, as well as for the study of metabolic diseases. This makes zebrafish an alternative model for studying the effects of energy disruption and nutritional quality on a wide range of behavioural aspects. Here, we used the zebrafish model to study how obesity induced by overfeeding regulates emotional and cognitive processes. Two groups of fish (n = 24 per group) were fed at 2% (CTRL) and 8% (overfeeding-induced obesity, OIO) for 8 weeks and tested for anxiety-like behaviour using the novel tank diving test (NTDT). Fish were first tested using a short-term memory test (STM) and then trained for four days for a long-term memory test (LTM). At the end of the experiment, fish were euthanised for biometric sampling, total lipid content, and triglyceride analysis. In addition, brains (eight per treatment) were dissected for HPLC determination of monoamines. Overfeeding induced faster growth and obesity, as indicated by increased total lipid content. OIO had no effect on anxiety-like behaviour. Animals were then tested for cognitive function (learning and memory) using the aversive learning test in Zantiks AD units. Results show that both OIO and CTRL animals were able to associate the aversive stimulus with the conditioned stimulus (conditioned learning), but OIO impaired STM regardless of fish sex, revealing the effects of obesity on cognitive processes in zebrafish. Obese fish did not show a deficiency in monoaminergic transmission, as revealed by quantification of total brain levels of dopamine and serotonin and their metabolites. This provides a reliable protocol for assessing the effect of metabolic disease on cognitive and behavioural function, supporting zebrafish as a model for behavioural and cognitive neuroscience.

Designing lisuride intranasal nanocarrier system for reduction of oxidative damage with enhanced dopamine level in brain for Parkinsonism

In the present study, nanoemulsion (NE) loaded with lisuride were formulated for delivering drug to brain via intranasal route. Dopamine levels, pharmacokinetic, and antioxidant activity were estimated. Antioxidant effect of lisuride NE was assessed in-vivo using oxidative stress models revealing symptoms like those of Parkinson's disease. Intranasally administered lisuride NE-treated group revealed a greater number of antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione (GSH) as compared to the intravenously administered lisuride suspension in haloperidol rat model. Additionally, it was observed that lisuride NE can decrease dopamine loss. When lisuride NE was administered intranasally resulted in considerably higher dopamine concentrations (17.48 ± 0.05 ng/mL) in comparison to rats receiving haloperidol (7.28 ± 0.02 ng/mL). From study, it is suggested that NE is a possible strategy to deliver lisuride intranasally to lower free radical damage and prevent the biochemical alterations associated with Parkinson's disease.

Patterns of ethanol intake in male rats with partial dopamine transporter deficiency.

Mesolimbic dopamine signaling plays a major role in alcohol and substance use disorders as well as comorbidities such as anxiety and depression. Growing evidence suggests that alcohol drinking is modulated by the function of the dopamine transporter (DAT), which tightly regulates extracellular dopamine concentrations. Adult male rats on a Wistar Han background (DAT+/+) and rats with a partial DAT deletion (DAT+/-) were used in this study. First, using fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens core from ethanol-naïve subjects, we measured greater evoked dopamine concentrations and slower dopamine reuptake in DAT+/- rats, consistent with increased dopamine signaling. Next, we measured ethanol drinking using the intermittent access two-bottle choice paradigm (20% v/v ethanol vs. water) across 5 weeks. DAT+/- rats voluntarily consumed less ethanol during its initial availability (the first 30 min), especially after longer periods of deprivation. In addition, DAT+/- males consumed less ethanol that was adulterated with the bitter tastant quinine. These findings suggest that partial DAT blockade and concomitant increase in brain dopamine levels has potential to reduce drinking and ameliorate alcohol use disorder (AUD).

CSF dopamine is elevated in first-episode psychosis and associates to symptom severity and cognitive performance.

The hypothesis of dopamine dysfunction in psychosis has evolved since the mid-twentieth century. However, clinical support from biochemical analysis of the transmitter in patients is still missing. The present study assessed dopamine and related metabolites in the cerebrospinal fluid (CSF) of first-episode psychosis (FEP) subjects. Forty first-episode psychosis subjects and twenty healthy age-matched volunteers were recruited via the Karolinska Schizophrenia Project, a multidisciplinary research consortium that investigates the pathophysiology of schizophrenia. Psychopathology, disease severity, and cognitive performance were rated as well as cerebrospinal fluid concentrations of dopamine and related metabolites were measured using a sensitive high-pressure liquid chromatography assay. CSF dopamine was reliably detected in 50% of healthy controls and in 65% of first-episode psychosis subjects and significantly higher in first-episode psychosis subjects compared to age-matched healthy controls. No difference in CSF dopamine levels was observed between drug-naive subjects and subjects with short exposure to antipsychotics. The dopamine concentrations were positively associated with illness severity and deficits in executive functioning. Dopamine dysfunction has long been considered a cornerstone of the pathophysiology of schizophrenia, although biochemical support for elevated brain dopamine levels has been lacking. The results of the present study, showing that FEP subjects have increased CSF dopamine levels that correlate to disease symptoms, should fill the knowledge gap in this regard.

Fluorescence microscopy-based sensitive method to quantify dopaminergic neurodegeneration in a Drosophila model of Parkinson's disease.

Death of dopaminergic (DAergic) neurons in the substantia nigra pars compacta of the human brain is the characteristic pathological feature of Parkinson's disease (PD). On exposure to neurotoxicants, Drosophila too exhibits mobility defects and diminished levels of brain dopamine. In the fly model of sporadic PD, our laboratory has demonstrated that there is no loss of DAergic neuronal number, however, a significant reduction in fluorescence intensity (FI) of secondary antibodies that target the primary antibody-anti-tyrosine hydroxylase (TH). Here, we present a sensitive, economical, and repeatable assay to characterize neurodegeneration based on the quantification of FI of the secondary antibody. As the intensity of fluorescence correlates with the amount of TH synthesis, its reduction under PD conditions denotes the depletion in the TH synthesis, suggesting DAergic neuronal dysfunction. Reduction in TH protein synthesis is further confirmed through Bio-Rad Stain-Free Western Blotting. Quantification of brain DA and its metabolites (DOPAC and HVA) using HPLC-ECD further demonstrated the depleted DA level and altered DA metabolism as evident from enhanced DA turnover rate. Together all these PD marker studies suggest that FI quantification is a refined and sensitive method to understand the early stages of DAergic neurodegeneration. FI quantification is performed using ZEN 2012 SP2, a licensed software from Carl Zeiss, Germany. This method will be of good use to biologists, as it with few modifications, can also be implemented to characterize the extent of degeneration of different cell types. Unlike the expensive and cumbersome confocal microscopy, the present method using fluorescence microscopy will be a feasible option for fund-constrained neurobiology laboratories in developing countries.

Cecal microbiota transplantation: unique influence of cecal microbiota from divergently selected inbred donor lines on cecal microbial profile, serotonergic activity, and aggressive behavior of recipient chickens

BackgroundAccumulating evidence from human trials and rodent studies has indicated that modulation of gut microbiota affects host physiological homeostasis and behavioral characteristics. Similarly, alterations in gut microbiota could be a feasible strategy for reducing aggressive behavior and improving health in chickens. The study was conducted to determine the effects of early-life cecal microbiota transplantation (CMT) on cecal microbial composition, brain serotonergic activity, and aggressive behavior of recipient chickens.MethodsChicken lines 63 and 72 with nonaggressive and aggressive behavior, respectively, were used as donors and a commercial strain Dekalb XL was used as recipients for CMT. Eighty-four 1-d-old male chicks were randomly assigned to 1 of 3 treatments with 7 cages per treatment and 4 chickens per cage (n = 7): saline (control, CTRL), cecal solution of line 63 (63-CMT), and cecal solution of line 72 (72-CMT). Transplantation was conducted via oral gavage once daily from d 1 to 10, and then boosted once weekly from week 3 to 5. At weeks 5 and 16, home-cage behavior was recorded, and chickens with similar body weights were assigned to paired aggression tests between the treatments. Samples of blood, brain, and cecal content were collected from the post-tested chickens to detect CMT-induced biological and microbiota changes.Results63-CMT chickens displayed less aggressive behavior with a higher hypothalamic serotonergic activity at week 5. Correspondingly, two amplicon sequence variants (ASVs) belonging to Lachnospiraceae and one Ruminococcaceae UCG-005 ASV were positively correlated with the levels of brain tryptophan and serotonin, respectively. 72-CMT chickens had lower levels of brain norepinephrine and dopamine at week 5 with higher levels of plasma serotonin and tryptophan at week 16. ASVs belonging to Mollicutes RF39 and GCA-900066225 in 72-CMT chickens were negatively correlated with the brain 5-hydroxyindoleacetic acid (5-HIAA) at week 5, and one Bacteroides ASV was negatively correlated with plasma serotonin at week 16.ConclusionResults indicate that CMT at an early age could regulate aggressive behavior via modulating the cecal microbial composition, together with central serotonergic and catecholaminergic systems in recipient chickens. The selected CMT could be a novel strategy for reducing aggressive behavior through regulating signaling along the microbiota-gut-brain axis.

Neuroethology: Perceived danger inhibits the wanting system of bees

A dopaminergic wanting system drives foraging in honey bees. A new study shows that encounters with the Asian hornet, a fierce bee predator, decrease brain dopamine levels and thus foraging. Stop signals, used to terminate the waggle dances of receivers, have the same effect, showing the power of bee communication.

An inhibitory signal associated with danger reduces honeybee dopamine levels

Positive and negative experiences can alter animal brain dopamine levels.1 When first arriving at a rewarding food source or beginning to waggle dance and recruit nestmates to food, honeybees have increased brain dopamine levels, indicating a desire for food.2 We provide the first evidence that an inhibitory signal, the stop signal, which counters waggle dancing and is triggered by negative events at the food source, can decrease head dopamine levels and dancing, independent of the dancer having any negative experiences. The hedonic value of food can therefore be depressed simply by the receipt of an inhibitory signal. Increasing the brain dopamine levels reduced the aversive effects of an attack, increasing the time that bees spent subsequently feeding and waggle dancing and decreasing their stop signaling and time spent in the hive. Because honeybees regulate food recruitment and its inhibition at the colony level, these results highlight the complex integration of colony information with a basic and highly conserved neural mechanism in mammals and insects.2 VIDEO ABSTRACT.

Amphetamine-induced prolonged disturbances in tissue levels of dopamine and serotonin in the rat brain

BackgroundA hallmark of psychostimulants is the persistence of neurobiological changes they produce. The difficulty in reversing long-time effects of psychostimulants use is why addiction therapy is so ineffective. This study aimed to look for such drug-induced changes that can be detected even after many weeks of abstinence.MethodsRats were given 12 doses of amphetamine (Amph) at 1.5 mg/kg. The rewarding effect of Amph was assessed using ultrasonic vocalization. After 14 and 28 days of abstinence, tissue levels of dopamine (DA), serotonin (5-HT), and their metabolites were measured in the prefrontal cortex (PFC), nucleus accumbens (Acb), dorsomedial (CPuM), and dorsolateral (CPuL) striatum.ResultsAfter 28 days of abstinence, DA levels were increased in the dorsal striatum while 5-HT levels were decreased in all brain regions studied. The opposite direction of changes in DA and 5-HT tissue levels observed in the dorsal striatum may be related to the changes in the emotional state during abstinence and may contribute to the incubation of craving and relapses. Tissue levels of 5-HT and DA showed intra- and inter-structural correlations, most pronounced after 14 days of abstinence. Most of them were absent in the control group (ctrl), which may indicate that their appearance was related to the changes induced by earlier Amph administration. We did not find any associations between reward sensitivity and the persistence of Amph-induced neurochemical disturbances.ConclusionsAdministration of 12 moderate doses of Amph causes prolonged changes in DA and 5-HT tissue levels. The direction and severity of the changes are dependent on the brain region and the neurotransmitter studied.

Food restriction and hyperactivity induce changes in corticolimbic brain dopamine and serotonin levels in female rats

Compelling data support altered dopamine (DA) and serotonin (5-HT) signaling in anorexia nervosa (AN). However, their exact role in the etiopathogenesis of AN has yet to be elucidated. Here, we evaluated the corticolimbic brain levels of DA and 5-HT in the induction and recovery phases of the activity-based anorexia (ABA) model of AN. We exposed female rats to the ABA paradigm and measured the levels of DA, 5-HT, the metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and the dopaminergic type 2 (D2) receptors density in feeding- and reward-implicated brain regions (i.e., cerebral cortex, Cx; prefrontal cortex, PFC; caudate putamen, CPu; nucleus accumbens, NAcc; amygdala, Amy; hypothalamus, Hyp; hippocampus, Hipp). DA levels were significantly increased in the Cx, PFC and NAcc, while 5-HT was significantly enhanced in the NAcc and Hipp of ABA rats. Following recovery, DA was still elevated in the NAcc, while 5-HT was increased in the Hyp of recovered ABA rats. DA and 5-HT turnover were impaired at both ABA induction and recovery. D2 receptors density was increased in the NAcc shell. These results provide further proof of the impairment of the dopaminergic and serotoninergic systems in the brain of ABA rats and support the knowledge of the involvement of these two important neurotransmitter systems in the development and progression of AN. Thus, providing new insights on the corticolimbic regions involved in the monoamine dysregulations in the ABA model of AN.

Bile duct ligation increased dopamine levels in the cerebral cortex of rats partly due to induction of tyrosine hydroxylase.

Liver failure is associated with psychiatric alterations, partly resulting from the increased brain dopamine levels. We investigated the relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and the mechanism by which liver failure increased dopamine levels in SH-SY5Y cells. Behavioural tests were carried out on day 13 and 27 following BDL, along with measurements of dopamine and metabolites, expressions of enzymes and transporters related to dopamine metabolism, and its transport into the cortex and the hippocampus. SH-SY5Y cells were used to investigate whether NH4 Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase or not. Tyrosine hydroxylase (TH) expression in SH-SY5Y cells co-incubated with bilirubin and signal pathway inhibitors was measured. Open-field test results demonstrated BDL rats showed anxiety-like behaviour, accompanied by increased dopamine levels and expression of TH protein in the cortex. Membrane bound long form (MB)-COMT, slightly but significantly decreased. SH-SY5Y cells indicated that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF-κB pathway BAY 11-7082 and silencing NF-κB p65 reversed bilirubin-induced upregulation of TH protein. NF-κB activator TNF-α increased expression of TH protein. Roles of bilirubin in increases of TH protein expressions and dopamine levels were measured using hyperbilirubinemia rats. Anxiety-like behaviour, was associated with increased dopamine levels and TH protein expressions in hyperbilirubinemia rats. BDL significantly increased dopamine levels in rat cortex partly due to bilirubin-mediated TH induction. Increased bilirubin induced TH expression via activating NF-κB signalling pathway.

Short-Term Effect of Spiritual Music on Heart Rate Variability in Medical Students: A Single-Group Experimental Study.

There are ancient texts and modern studies alluding to the therapeutic benefits obtained from listening to music. Studies have shown that chanting "OM" has a relaxing effect by causing parasympathetic dominance, limbic deactivation, and decreasing the brain's dopamine levels. This research aims to study the effect of listening to OM chanting on the cardiovascular system and heart rate variability and its possible use as a stress buster among medical students. Fifty medical undergraduates were selected for the study. After a 20-minute relaxation, a lead 2 electrocardiogram (EKG) was recorded for 10 minutes. Their blood pressure (BP) and heart rate were measured. The subjects were then made to listen to OM chanting for 20 minutes, immediately after which their BP and heart rate were measured. This was followed by another 10-minute lead 2 EKG. The EKGs recorded were then used to calculate the standard deviation in N-N interval (SDNN), total power, high-frequency power, and low-frequency power. The study reported a significant decrease in blood pressure and heart rate and a significant increase in SDNN and total power. There was also an insignificant increase in low frequency and an insignificant decrease in high frequency. This study provides insight into the importance of spiritual music therapy in the maintenance of mental as well as cardiovascular health among medical students.

Effects of walnut (Juglans regia L.) kernel extract and juglone on dopamine levels and oxidative stress in rats

3,4-dihydroxyphenethylamine (dopamine) is a neurotransmitter that has vital functions in the nervous system. Dopamine metabolism and reactive oxygen species (ROS) production are highly related processes. The present study aims to evaluate the effects of walnut (Juglans regia L.) extract (WE) and 5-hydroxy-1,4 naphthoquinone (juglone) on dopamine levels and oxidative stress. For this purpose, WE and juglone were administered to rats. Serum and brain dopamine levels, total oxidant status (TOS), and total antioxidant status (TAS) were measured after 21 days. The oxidative stress index (OSI) was calculated. WE (300 mg/kg) significantly increased brain dopamine levels. WE and juglone reduced oxidative stress in liver and brain tissues compared to serum. Our results revealed that WE and juglone might have a neuroprotective effect. Further studies are needed to extensively investigate the molecular mechanism of the effects of herbal extracts and phenolic compounds on brain health.

Neuroprotective Effects of P-Coumaric Acid on Haloperidol-Induced Catalepsy Through Ameliorating Oxidative Stress and Brain Dopamine Level

Objective To evaluate the effect of p-coumaric acid (p-CA) on haloperidol-induced catalepsy in Swiss albino male mice. Methods To induce catalepsy, haloperidol (1 mg/kg i.p.) was administered for 21 consecutive days. p-CA (50, 75, and 100 mg/kg, PO) was administered 30 min before haloperidol injection for 21 consecutive days. For catalepsy, locomotor activity and motor coordination scores were recorded on the 17, 14, and 21 days of drug treatment, while the gait analysis score was recorded on day 21. After behavioral testing, animals were sacrificed, and various biochemical and histopathology tests of the brain were conducted. Dopamine, malondialdehyde, reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activity were examined in the brain. Results Chronic administration of haloperidol significantly increased catalepsy in mice. It also produced hypolocomotion, motor coordination, and gait disturbance in mice. p-CA significantly inhibited haloperidol-induced catalepsy. Haloperidol significantly increased malondialdehyde levels in the brain. While dopamine levels in the brain dropped along with GSH, SOD, and catalase activity levels, which also had an impact on the histology of the brain. p-CA significantly reduced haloperidol-induced increases in brain oxidative stress, dopamine levels in the brain, and brain histology in mice. Discussion p-CA significantly reduced haloperidol-induced catalepsy, possibly through reducing oxidative stress and increasing brain dopamine levels. It can be a good candidate drug for extrapyramidal symptoms in Parkinson’s disease and adjuvant therapy with antipsychotic drugs.

Effects of mitophagy on aerobic exercise intervention for depression in rats

Objective: This experiment was designed to observe the effects of aerobic exercise on depressive behavior in rats induced by chronic unpredictable mild stress (CUMS), and to explore the possible mechanism by detecting the proteins related to mitochondrial autophagy. Methods: SD rats were randomly divided into three groups: blank control group (C, n=12), depression model group (D, n=12) and post-depression exercise group (D+E, n=12). Group D and D+E were modeled with CUMS for 28 days, and group D+E underwent aerobic exercise intervention for 4 weeks after model establishment. Then the behavior of rats was evaluated. The concentrations of whole brain dopamine and norepinephrine were determined by ELISA kits. The morphology and structure of mitochondria in the frontal lobe were observed with the transmission electron microscope (TEM). Mitochondrial autophagy lysosomes were localized by immunofluorescence colocalization. The expressions of LC3 and P62 proteins in the frontal lobe were measured with Western Blotting. The relative content of mitochondrial DNA was detected using Real-time PCR. Results: ①Compared with group C, the sucrose preference ratio in group D was decreased significantly(P＜0.01); Compared with group D, the sucrose preference ratio in group D+E was increased significantly (P＜0.01). ②In the open field experiment, compared with group C, group D had a significant decrease in activity, average speed and total distance (P＜0.05); Compared with group D, the average rate of activity in group D+E was significantly higher (P＜0.05). ③ELISA results showed that the levels of whole brain dopamine and norepinephrine were significantly lower in group D rats than those in group C (P＜0.05). ④Under transmission electron microscopy, compared with group C, group D had different degrees of mitochondrial swelling, decreased crest density, and intermembrane space dilation.; Compared with group D, a significant increase in mitochondrial autophagosomes and autophagic lysosomes was observed in neurons in group D+E. Increased co-localization of mitochondria with lysosomes in the D+E group could be observed under fluorescence microscopy. ⑤Compared with group C, the expression of P62 was increased significantly(P＜0.05), and LC3II/LC3I ratio was decreased significantly (P＜0.05) in group D; Compared with group D, LC3II/LC3I ratio was significantly higher in group D+E than that in group D (P＜0.05). ⑥Compared with group C, the relative number of mitochondrial DNA in the frontal lobe of group D was increased significantly (P＜0.05). Conclusion: Aerobic exercise has a significant improvement effect on depression induced by CUMS in rats, and its mechanism may be related to the upregulation of the level of linear autophagy.

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains.

Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio.

Alhagi maurorum Ethanolic Extract Rescues Hepato-Neurotoxicity and Neurobehavioral Alterations Induced by Lead in Rats via Abrogating Oxidative Stress and the Caspase-3-Dependent Apoptotic Pathway.

This work investigated the probable protective effect of an Alhagi maurorum ethanolic extract on the hepatotoxicity and neurotoxicity accompanied by neurobehavioral deficits caused by lead in rats. Rats in four groups were orally administered distilled water, ethanolic extract of A. maurorum (300 mg/kg BW daily), lead (100 mg/kg BW daily for 3 months), and lead + A. maurorum extract. The results demonstrated that lead exposure resulted in elevated locomotor activities and sensorimotor deficits associated with a decrease in brain dopamine levels. Moreover, lead exposure significantly increased liver function markers. In addition, the lead-treated rats exhibited extensive liver and brain histological changes and apoptosis. The lead treatment also triggered oxidative stress, as demonstrated by the increase in malondialdehyde (MDA) concentrations with a remarkable reduction in the activities of antioxidant enzymes, reduced glutathione (GSH) levels, and transcriptional mRNA levels of antioxidant genes in the liver and brain. Nevertheless, co-treatment with the A. maurorum extract significantly ameliorated the lead-induced toxic effects. These findings indicate that the A. maurorum extract has the ability to protect hepatic and brain tissues against lead exposure in rats through the attenuation of apoptosis and oxidative stress.

EFFECT OF HALOPERIDOL ON SELECTED OXIDATIVE STRESS PARAMETERS AND DOPAMINE LEVEL IN RATS BRAIN

The present study was conducted to assess the effects of haloperidol (psychiatric drug ) on some oxidative stress parameters (GSH and lipid peroxidation product MDA) and it's relation to the dopamine level in rats' brain.Twenty-four male Sprague- Dawely rats were enrolled in this study. They were randomly separated into three groups, eight rats in each group: Group 1, (normal control group), eight rats were put on normal chow diet for 45 days from which the baseline value of selected parameters were measured. Group 2 (self control group) on distilled water orally administered by stomach tube for 45 days. Group 3 on Haloperidol 1 mg/kg orally administered by stomach tube for 45 days.After decapitation, brain were removed from rats and homogenized from which GSH, MDA, and dopamine levels were measured. This study revealed the following results.1- Administration of haloperidol was highly significant (P value &lt; 0.01) decreased the GSH and dopamine level in rats' brain.2- Administration of haloperidol was highly significant (P value &lt; 0.01) increased the MDA levels in rats' brain.It was concluded that haloperidol is a potent inducer of oxidative stress and highly decreased the levels of dopamine in rats' brain.