Graybowers3771

Perinatal depression (PND) affects approximately 15% of women, and de novo postpartum depression affects approximately 40% of PND cases. Selective serotonin reuptake inhibitors (SSRIs) are a common class of antidepressants prescribed to treat PND. However, the safety and efficacy of SSRIs have been questioned in both clinical and preclinical research. Here, using a preclinical rodent model of de novo postpartum depression, we aim to better understand neuroinflammatory cytokines and tryptophan mechanisms that may be related to SSRI efficacy. Rat dams were treated with high corticosterone (CORT; 40 mg/kg, s.c.) for 22 days in the postpartum period to simulate a depressive-like endophenotype. Concurrently, a subset of dams was treated with the SSRI, fluoxetine (FLX; 10 mg/kg, s.c.), in the postpartum period. We showed, consistent with previous studies, that although maternal FLX treatment prevented CORT-induced disturbances in maternal care behavior during the early postpartum, it failed to prevent the expression of CORT-induced passive coping behavior in the late postpartum. Furthermore, FLX treatment, regardless of CORT treatment, increased maternal hippocampal IL-1β, plasma CXCL1, and decreased maternal plasma tryptophan, 4'-pyridoxic acid, and pyridoxal concentrations. Maternal CORT treatment reduced maternal hippocampal IFN-γ, and both hippocampal and plasma TNF-α. Our work suggests that the limited efficacy of FLX in the late postpartum may be associated with elevated levels of the proinflammatory cytokine IL-1β in the maternal hippocampus, elevated plasma CXCL1, decreased plasma tryptophan concentration, and changes in vitamin B6 dependent tryptophan-kynurenine pathway. These findings suggest novel pathways for improving SSRI efficacy in alleviating perinatal depression.Alcohol use disorder (AUD) places a tremendous burden on society, with approximately two billion alcohol users in the world. While most people drink alcohol recreationally, a subpopulation (3-5%) engages in reckless and compulsive drinking, leading to the development of AUD and alcohol dependence. The Ventral Tegmental Area (VTA)-Nucleus Accumbens (NAc) circuit has been shown to encode rewarding stimuli and drive individual alcohol drinking behavior. Our previous work successfully separated C57BL/6J isogenic mice into high or low alcohol drinking subgroups after a 12-day, two-bottle choice voluntary alcohol access paradigm. Electrophysiological studies revealed that low alcohol drinking mice exhibited elevated spontaneous and burst firing properties of their VTA dopamine (DA) neurons and specifically mimicking this pattern of activity in VTA-NAc neurons in high alcohol drinking mice using optogenetics decreased their alcohol preference. It is also known that VTA DA neurons encode the salience and rewarding properties of external stimuli while also regulating downstream dopamine concentrations. Here, as a follow-up to this study, we utilized Fast Scan Cyclic Voltammetry (FSCV) to examine dopamine release in the NAc shell and core between alcohol drinking groups. We observed dynamic changes of dopamine release in the core of high drinking mice, but failed to see widely significant differences of dopamine release in the shell of both groups, when compared with ethanol-naive controls. Overall, the present data suggest subregion-specific differences of evoked dopamine release in the NAc of low and high alcohol drinking mice, and may provide an anatomical substrate for individual alcohol drinking behavior.Parkinson's disease (PD) is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to motor symptoms. Despite the remarkable improvements in the management of PD in recent decades, many patients remain significantly disabled. Metformin is a primary medication for the management of type 2 diabetes. We previously showed that co-treatment with metformin and 3,4-dihydroxyphenyl-l-alanine (l-DOPA) prevented the development of l-DOPA-induced dyskinesia in a 6-hydroxydopamine (6-OHDA)-lesioned animal model of PD. However, effects of metformin on PD- and aging-induced genes in reactive astrocytes remain unknown. In this study, we assessed the effect of metformin on motor function, neuroprotection, and reactive astrocytes in the 6-OHDA-induced PD animal model. In addition, the effects of metformin on the genes expressed by specific types of astrocytes were analyzed in PD model and aged mice. Here, we showed that metformin treatment effectively improves the motor symptoms in the 6-OHDA-induced PD mouse model, whereas metformin had no effect on tyrosine hydroxylase-positive neurons. The activation of AMPK and BDNF signaling pathways was induced by metformin treatment on the 6-OHDA-lesioned side of the striatum. Metformin treatment caused astrocytes to alter reactive genes in a PD animal model. Moreover, aging-induced genes in reactive astrocytes were effectively regulated or suppressed by metformin treatment. Taken together, these results suggest that metformin should be evaluated for the treatment of Parkinson's disease and related neurologic disorders characterized by astrocyte activation.The popularity of e-cigarettes has skyrocketed in recent years, and most vapers use flavored e-cigarette products. Consumption of flavored e-cigarettes exceeds that of combustible cigarettes and other tobacco products among adolescents, who are particularly vulnerable to becoming nicotine dependent. Flavorings have been used by the tobacco industry since the 17th century, but the use of flavors by the ecigarette industry to create products with "characterizing" flavors (i.e. flavors other than tobacco or menthol) has sparked a public health debate. This review addresses the possibility that characterizing flavors make nicotine more appealing, rewarding and addictive. It also discusses ways in which preclinical and clinical studies could improve our understanding of the mechanisms by which flavors may alter nicotine reward and reinforcement.In arid conditions, the African Clawed frog Xenopus laevis enters a state of estivation dormancy as an adaptive survival strategy. Under estivation, X. Selleckchem Iadademstat laevis experience severe dehydration stress as 25-35% of total body water is lost. Dehydration in X. laevis can lead to periods of hypoxia due to elevated blood viscosity that impedes tissue perfusion. To understand how X. laevis survives under such stress, we studied the regulation pattern of key mitogen-activated protein kinases (MAPK) and their downstream transcription factors, along with several heat shock proteins in the oxygen sensitive brain and heart tissue of X. laevis under dehydration stress. Our study revealed that the activation phosphorylation residues of MAPK including JNK and MSK and their downstream transcription factors c-Jun and ATF2 are significantly decreased in the heart under dehydration. Given that JNK, c-Jun, and ATF2 are known positive regulators of apoptosis, this regulatory pattern suggest that a state of pro-survival signals may be established in the dehydrated heart.