Serotonin (5-HT) and its receptors have been implicated in various neuropsychiatric disorders. Altered serotonergic neurotransmission and interactions between 5-HT and dopamine (DA) systems may ...contribute to the pathophysiology of idiopathic psychotic or manic disorders. Interactions with 5-HT receptors may also contribute to special properties of modern antipsychotic drugs not yet evaluated for long-term effects on 5-HT receptors.
We surveyed effects of newer atypical antipsychotics on 5-HT receptor types 1A, 2A, and 2C in rat forebrain regions by quantitative receptor autoradiography with selective radioligands following 28 days of continuous infusion of drugs or control vehicle.
Infusion of olanzapine, risperidone, and quetiapine increased 1A, but decreased 2A receptor labeling in frontal cerebral cortex. Olanzapine decreased binding at 2C receptors in hippocampal CA(1) and CA(3) regions and perhaps entorhinal cortex; olanzapine, but neither risperidone nor quetiapine, also decreased 2C labeling in caudate-putamen.
The findings suggest that altered 5-HT(1A) and 5-HT(2A)receptor levels in frontal cortex, and 5-HT(2C) receptors in other forebrain regions, may contribute to psychopharmacological properties of these novel atypical antipsychotic agents, perhaps including their antipsychotic or antimanic actions, and low risk of adverse extrapyramidal effects.
Changes in members of the dopamine (DA) D(1)-like (D(1), D(5)) and D(2)-like (D(2), D(3), D(4)) receptor families in rat forebrain regions were compared by quantitative in vitro receptor ...autoradiography after prolonged treatment (28 days) with the atypical antipsychotics olanzapine, risperidone, and quetiapine. Olanzapine and risperidone, but not quetiapine, significantly increased D(2) binding in medial prefrontal cortex (MPC; 67% and 34%), caudate-putamen (CPu; average 42%, 25%), nucleus accumbens (NAc; 37%, 28%), and hippocampus (HIP; 53%, 30%). Olanzapine and risperidone, but not quetiapine, produced even greater up-regulation of D(4) receptors in CPu (61%, 37%), NAc (65%, 32%), and HIP (61%, 37%). D(1)-like and D(3) receptors in all regions were unaltered by any treatment, suggesting their minimal role in mediating actions of these antipsychotics. The findings support the hypothesis that antipsychotic effects of olanzapine and risperidone are partly mediated by D(2) receptors in MPC, NAc, or HIP, and perhaps D(4) receptors in CPu, NAc, or HIP, but not in cerebral cortex. Selective up-regulation of D(2) receptors by olanzapine and risperidone in CPu may reflect their ability to induce some extrapyramidal effects. Inability of quetiapine to alter DA receptors suggests that nondopaminergic mechanisms contribute to its antipsychotic effects.
Depression is a major mental health condition and is expected be the most debilitating and widespread health disorder by 2030. Tuberculosis (TB) is also a leading cause of morbidity and mortality ...worldwide and interestingly, is a common comorbidity of depression. As such, much attention has been paid to the association between these 2 pathologies. Based on clinical reports, the association between TB and depression seems to be bidirectional, with a substantial overlap in symptoms between the 2 conditions. TB infection or reactivation may precipitate depression, likely as a consequence of the host's inflammatory response and/or dysregulation of the hypothalamic–pituitary–adrenal axis. Nevertheless, few studies have considered whether patients with depression are at a higher risk for TB. In this review, we discuss the hypotheses on the association between depression and TB, highlighting the immuno‐inflammatory response and lipid metabolism as potential mechanisms. Improving our understanding of the interplay between these 2 disorders should help guide TB clinical care and prevention both in patients with comorbid depression and in the general population.
Review on the association between depression and tuberculosis, includes a potential mechanism underlying depression's role in increasing the risk for tuberculosis.
Levels of ionotropic glutamate (Glu) N-methyl-d-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainic acid (KA) receptors in rat forebrain regions were ...compared by quantitative in vitro receptor autoradiography after continuous treatment for 28 days with the atypical antipsychotics olanzapine, risperidone, and quetiapine, or vehicle controls. All three treatments significantly decreased NMDA binding in caudate-putamen (CPu; by 30, 34, and 26%, respectively) but increased AMPA receptor levels in same region (by 22, 30, and 28%). Olanzapine and risperidone, but not quetiapine, also reduced NMDA receptor labeling in hippocampal CA1 (21 and 19%) and CA3 (23 and 22%) regions. KA receptors were unaltered by any treatment in the brain regions examined. These findings suggest that the antipsychotic effects of olanzapine and risperidone may be mediated in part by NMDA receptors in hippocampus, and perhaps AMPA receptors in CPu. The findings also support the hypothesis that down-regulation of NMDA receptors by atypical antipsychotic agents in CPu contributes to their low risk of extra-pyramidal side effects. Inability of olanzapine, risperidone, and quetiapine to alter KA receptors suggests their minimal role in mediating the central nervous system actions of these drugs.
Attention-deficit hyperactivity disorder (ADHD) involves clinically heterogeneous dysfunctions of sustained attention, with behavioral overactivity and impulsivity, of juvenile onset. Experimental ...models, in addition to mimicking syndromal features, should resemble the clinical condition in pathophysiology, and predict potential new treatments. One of the most extensively evaluated animal models of ADHD is the spontaneously hypertensive rat. Other models include additional genetic variants (dopamine transporter gene knock-out mouse, coloboma mouse, Naples hyperexcitable rat, acallosal mouse, hyposexual rat, and population-extreme rodents), neonatal lesioning of dopamine neurons with 6-hydroxydopamine, and exposure to other neurotoxins or hippocampal irradiation. None is fully comparable to clinical ADHD. The pathophysiology involved varies, including both deficient and excessive dopaminergic functioning, and probable involvement of other monoamine neurotransmitters. Improved models as well as further testing of their ability to predict treatment responses are required.
Tuberculosis (TB) is a chronic infectious disease caused by mycobacterium tuberculosis (Mtb) that poses a major threat to human health.
Herein, we aim to review the alteration of the microbiota in ...gut and respiratory during TB development, the potential function and mechanisms of microbiota in the pathogenesis of Mtb infection, and the impact of antibiotic treatment on the microbiota. In addition, we discuss the potential new paradigm for the use of microbiota-based treatments such as probiotics and prebiotics in the treatment of TB.
Studies have shown that trillions of micro-organisms live in the human gut and respiratory tract, acting as gatekeepers in maintaining immune homeostasis and respiratory physiology and playing a beneficial or hostile role in the development of TB. Anti-TB antibiotics may cause microecological imbalances in the gut and respiratory tract, and microbiome-based therapeutics may be a promising strategy for TB treatment. Appropriate probiotics and prebiotics supplementation, along with antimycobacterial treatment, will improve the therapeutic effect of TB treatment and protect the gut and respiratory microbiota from dysbiosis.
Using two-dimensional Langevin dynamics simulations, we investigate the dynamics of polymer translocation into a confined space under a driving force through a nanopore, with particular emphasis on ...the chain stiffness and the shape of the confinement. We observe that with increasing the chain stiffness κ, the translocation time τ always increases for different shapes of confinements. For an ellipse, τ is different for the translocation through its minor and major axis directions. Under the weak confinement, the translocation through the minor axis direction is faster than that through the major axis direction for different κ, while this is true only for high κ under strong confinement. Particularly, for both weak and strong confinements we find that packaging into an ellipse through its minor axis direction is faster than that for a circle of the same area for high κ. These results are interpreted by the chain conformation during the translocation process and the time of an individual segment passing through the pore.
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