Tumors in invertebrates

Tumors are ectopic masses of tissue formed by due to an abnormal cell proliferation. In this review tumors of several invertebrate species are examined. The description of tumors in invertebrates may be a difficult task, because the pathologists are usually inexperienced with invertebrate tissues, and the experts in invertebrate biology are not familiar with the description of tumors. As a consequence, the terminology used in defining the tumor type is related to that used in mammalian pathology, which can create misunderstandings in some occasions

Lymnaea stagnalis as model of neuropsychiatric disorders

This paper describes the advantages of adopting a molluscan model for studying the biological basis of some central nervous system pathologies affecting humans. In particular, I will focus on the freshwater snail Lymnaea stagnalis, which is already the subject of electrophysiological studies related to learning and memory, as well as ecotoxicological studie

Circulating phagocytes: The ancient and conserved interface between immune and neuroendocrine function

Immune and neuroendocrine functions display significant overlap in highly divergent and evolutionarily distant models such as molluscs, crustaceans, insects and mammals. Fundamental players in this crosstalk are professional phagocytes: macrophages in vertebrates and immunocytes in invertebrates. Although they have different developmental origins, macrophages and immunocytes possess comparable functions and differentiate under the control of evolutionarily conserved transcription factors. Macrophages and immunocytes share their pools of receptors, signalling molecules and pathways with neural cells and the neuro-endocrine system. In crustaceans, adult transdifferentiation of circulating haemocytes into neural cells has been documented recently. In light of developmental, molecular and functional evidence, we propose that the immune-neuroendocrine role of circulating phagocytes pre-dates the split of protostomian and deuterostomian superphyla and has been conserved during the evolution of the main groups of metazoans

Molecular changes associated with escitalopram response in a stress-based model of depression

Converging evidence points at hypothalamus-pituitary-adrenal (HPA) axis hyperactivity and neuroinflammation as important factors involved in the etiopathogenesis of major depressive disorder (MDD) and in therapeutic efficacy of antidepressants. In this study, we examined the molecular effects associated with a response to a week-long treatment with escitalopram in the chronic escape deficit (CED) model, a validated model of depression based on the induction of an escape deficit after exposure of rats to an unavoidable stress. We confirmed our previous result that a treatment with escitalopram (10 mg/kg) was effective after 7 days in reverting the stress-induced escape deficit in approximately 50% of the animals, separating responders from non-responders. Expression of markers of HPA axis functionality as well as several inflammatory mediators were evaluated in the hypothalamus, a key structure integrating signals from the neuro, immune, endocrine systems. In the hypothalamus of responder animals we observed a decrease in the expression of CRH and its receptors and an increase in GR protein in total and nuclear extracts; this effect was accompanied by a significant decrease in circulating corticosterone in the same cohort. Hypothalamic IL-1\uce\ub2 and TNF\uce\ub1 expression were increased in stressed animals, while CXCL2, IL-6, and ADAM17 mRNA levels were decreased in escitalopram treated rats regardless of the treatment response. These data suggest that efficacy of a one week treatment with escitalopram may be partially mediated by a decrease HPA axis activity, while in the hypothalamus the drug-induced effects on the expression of immune modulators did not correlate with the behavioural outcome

Disease-induced neuroinflammation and depression

Progression of major depression, a multifactorial disorder with a neuroinflammatory signature, seems to be associated with the disruption of body allostasis. High rates of comorbidity between depression and specific medical disorders, such as, stroke, chronic pain conditions, diabetes mellitus, and human immunodeficiency virus (HIV) infection, have been extensively reported. In this review, we discuss how these medical disorders may predispose an individual to develop depression by examining the impact of these disorders on some hallmarks of neuroinflammation known to be impaired in depressed patients: altered permeability of the blood brain barrier, immune cells infiltration, activated microglia, increased cytokines production, and the role of inflammasomes. In all four pathologies, blood brain barrier integrity was altered, allowing the infiltration of peripheral factors, known to activate resident microglia. Evidence indicated morphological changes in the glial population, increased levels of circulating pro-inflammatory cytokines or increased production of these mediators within the brain, all fundamental in neuroinflammation, for the four medical disorders considered. Moreover, activity of the kynurenine pathway appeared to be enhanced. With respect to the inflammasome NLRP3, a new target whose role in neuroinflammation is emerging as being important, accumulating data suggest its involvement in the pathogenesis of brain injury following stroke, chronic pain conditions, diabetes mellitus or in HIV associated immune impairment. Finally, data gathered over the last 10 years, indicate and confirm that depression, stroke, chronic pain, diabetes, and HIV infection share a combination of underlying molecular, cellular and network mechanisms leading to a general increase in the neuroinflammatory burden for the individual

The proinflammatory cytokine interleukin 18 regulates feeding by acting on the bed nucleus of the stria terminalis

The proinflammatory cytokine IL-18 has central anorexigenic effects and was proposed to contribute to loss of appetite observed during sickness. Here we tested in the mouse the hypothesis that IL-18 can decrease food intake by acting on neurons of the bed nucleus of the stria terminalis (BST), a component of extended amygdala recently shown to influence feeding via its projections to the lateral hypothalamus (LH). We found that both subunits of the heterodimeric IL-18 receptor are highly expressed in the BST and that local injection of recombinant IL-18 (50 ng/ml) significantly reduced c-fos activation and food intake for at least 6 h. Electrophysiological experiments performed in BST brain slices demonstrated that IL-18 strongly reduces the excitatory input on BST neurons through a presynaptic mechanism. The effects of IL-18 are cell-specific and were observed in Type III but not in Type I/II neurons. Interestingly, IL-18-sensitve Type III neurons were recorded in the juxtacapsular BST, a region that contains BST-LH projecting neurons. Reducing the excitatory input on Type III GABAergic neurons, IL-18 can increase the firing of glutamatergic LH neurons through a disinhibitory mechanism. Imbalance between excitatory and inhibitory activity in the LH can induce changes in food intake. Effects of IL-18 were mediated by the IL-18R because they were absent in neurons from animals null for IL-18R\u3b1 (Il18ra-/-), which lack functional IL-18 receptors. In conclusion, our data show that IL-18 may inhibit feeding by inhibiting the activity of BST Type III GABAergic neurons

Cellular mechanisms and second messengers: relevance to the psychopharmacology of bipolar disorders

The discovery of lithium's efficacy as a mood-stabilizing agent revolutionized the treatment of patients with bipolar disorder and after five decades, lithium continues to be the mainstay of treatment for bipolar disorder. Recent research on the molecular mechanism underlying the therapeutic effect of lithium has focused on how it changes the activities of cellular signal transduction systems, especially the cyclic AMP and phosphomositide second-messenger systems. Considerable data suggest that carbamazepine and valproate (VPA) are an alternative or adjunctive treatment to lithium. VPA, despite being dissimilar structurally to lithium, shares most of the effects of lithium at the level of protein kinase C (PKC). Like lithium, VPA reduces the activity of PKC and reduces the protein levels of different PKC isoforms, however the effects of VPA appear to be largely independent of inositol. The ton-term efficacy of VPA and lithium in bipolar disorder suggested that modulation of gene expression might be an important target for these drugs. Both VPA and lithium altered the expression of the early inducible genes for c-fos and cjun thus promoting the expression of specific proteins. The genes known to be regulated by the AP-1 family of transcription factors include genes for various neuropeptides, neurotrophins, receptors, transcription factors, enzymes, proteins that bind to cytoskeletal elements, and cytoprotective proteins such as bcl-2. In conclusion chronic treatment with lithium and other mood stabilizers, by regulating transcriptional factors, may modulate the expression of a variety of genes that compensate for aberrant signalling associated with the pathophysiology of bipolar disorder

Transcriptional effect of serotonin in the ganglia of Lymnaea stagnalis

The serotonin system (5HT) is highly conserved in both vertebrates and invertebrates, and numerous evidence supports a biological link between 5HT and numerous animal function. In the present paper we evaluated the transcriptional effects of a serotonergic stimulation on selected targets involved in 5HT signalling and neurotransmission in the central nervous system of the great pond snail Lymnaea stagnalis. Adult snails were treated acutely (6 h) or chronically (48 h) with either 5-hydroxytrypthophan (5-HTP 1mM), the immediate precursor of serotonin, fluoxetine (FLX 1μM), a selective serotonin reuptake inhibitor, or a combination of two. The central ring ganglia were dissected and used for q-PCR gene expression analysis. Transcription was strongly induced following a chronic, but not an acute, exposure to 5-HTP in the ganglia of Lymnaea. In particular, LymCREB1 and LymP2X mRNA levels were decreased following a 6 h exposure and increased in snails receiving 5-hydroxytryptophan for 48 h. Interestingly, this effect was reduced when snails were exposed chronically to both 5-HTP and FLX, suggesting a role for SERT in mediating the effect of 5-hydroxytryptophan. These data suggest that L. stagnalis is suited to unravel the complexity of the serotonin signaling pathway