Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Effect of Fluoxetine Hydrochloride on Routine Metabolism of Lambari (Deuterodon iguape, Eigenmann, 1907) and Phantom Shrimp (Palaemon pandaliformis, Stimpson, 1871)

HIGHLIGHTS Fluoxetine increases the metabolic rate and excretion of ammonia in both species. O:N ratio in fish showed higher values in the highest concentrations of fluoxetine. The LC50 - 96 hour values of Palaemon pandaliformis represented greater toxicity. Both species are a good biological model for fluoxetine exposure studies.

Abstract Fluoxetine is an emerging pollutant that acts as a selective serotonin reuptake inhibitor (SSRI) and being a hydrolytic molecule that is photolytically stable and accumulaties in biological tissues, its disposal in the aquatic environment can interfere with the physiology of fish and shrimp. Thus, the objective of this study was to analyze the effects of fluoxetine on routine metabolism (metabolic rate, specific ammonia excretion and O:N ratio) of Deuterodon iguape and Palaemon pandaliformis. For this, five groups of each species, were exposed to different concentrations of fluoxetine for 24 hours (D. iguape) and 2 hours (P. pandaliformis). The results demonstrated that in D. iguape exposure to fluoxetine significantly increased both the metabolic rate by 75%, 85%, 55% and 50% for concentrations of 0.05; 0.1; 0.5 and 1.0 mgL-1, respectively, and the specific ammonia excretion by 40%, 48% and 20% for concentrations of 0.05; 0.1 and 0.5 mgL-1, respectively, when compared with their control. The O:N ratio was statistically greater in concentrations of 0.5 and 1.0 mgL-1. Concerning P. pandaliformis, exposure to fluoxetine increased metabolic rate at concentrations 30.0 and 60.0 µgL-1, and also increased specific ammonia excretion at concentrations 10.0, 30.0 and 60.0 µgL-1, when compared with the control group. It was concluded that exposure to fluoxetine increases the routine metabolism of both species and that at the concentration 1.0 mgL-1, Deuterodon iguape required different energy substrates.

Expressão neuroanatômica de c-Fos em ratos alimentados e em jejum após administração periférica aguda de fluoxetina / Neuroanatomical expression of c-Fos in fed and fasted rats after acute periferical fluoxetine administration

A fluoxetina é um inibidor seletivo de recaptação de serotonina que rapidamente promove aumento da disponibilidade sináptica deste neurotransmissor. A ativação do sistema serotoninérgico central pela fluoxetina, por sua vez, pode ser diferencialmente afetada pelo estado metabólico do animal. No presente estudo investigamos os efeitos da administração aguda de fluoxetina na expressão de c-Fos no cérebro de ratos em duas condições metabólicas distintas: alimentados e em jejum. DESENHO DO ESTUDO: Estudo tipo experimental. Ratos machos Wistar, pesando 220 ::t 30 g, foram sacrificados 2 horas após injeções intraperitoneais de salina (1 mVkg) ou fluoxetina (10 mg/kg). Após perfusão intracardíaca com solução tampão salina fosfato, seguida de paraformaldeído, os cérebros dos animais foram removidos, sendo posteriormente processada a imuno-histoquímica. A imunorreatividade para c-Fos foi quantificada por um sistema computadorizado (Image-Pro, Discovery). Tanto os animais tratados com fluoxetina no estado de jejum quanto no estado alimentado, apresentaram aumento significativo na expressão de c-Fos, comparados ao tratamento com salina, em algumas áreas hipotalâmicas, límbicas, circunventriculares, romboencefálicas e mesencefálicas. A comparação quantitativa dos dados obtidos dos animais alimentados e em jejum tratados com fluoxetina revelou que ratos no estado de jejum apresentaram expressão de c-Fos significativamente maior no hipotálamo ventromedial e núcleo paraventricular, comparados aos animais no estado alimentado...

Inhibition of tryptophan-pyrrolase activity and elevation of brain tryptophan concentration by fluoxetine in rats

To investigate in-vitro as well as in-vivo effects of various doses of fluoxetine [SSRI] on tryptophan metabolism in rats. Design: A pre-clinical study. Place and Duration of Study: Clinical Biochemistry Research Laboratory, Department of Biochemistry, University of Karachi. The investigation was carried out during 2000 to 2001. Subjects and Male Wistar rats [150-200 g body wt] were selected and divided into control and test groups [n = 5] for comparison. In in-vitro [10 - 1000mM] as well in-vivo [0.5 ' 30 mg/kg body wt.] studies, fluoxetine showed a statistically significant inhibition of rat liver tryptophan pyrrolase [tryptophan-2,3-dioxygenase; EC 1.13.11.11] activity. Significant increases were noted at 10 and 30 mg/kg doses in brain, serum [total and free] and liver L-tryptophan concentrations. Similarly, serum non-estrified free fatty acids showed a significant increase at both doses. There was no effect on serum glucose and albumin concentrations. It is suggested that major mechanism of action of fluoxetine is that of elevating brain tryptophan concentration and hence 5-HT synthesis by increasing the availability of circulating tryptophan to the brain secondarily to inhibition of major tryptophan degrading enzyme, hepatic tryptophan pyrrolase. It is assumed that fluoxetine inhibits the binding of apoenzyme form of tryptophan pyrrolase with its cofactor haem. The results are discussed in relation to possible involvement of disturbed hepatic tryptophan metabolism in depressive illness