Proteomic evidence of depression-associated astrocytic dysfunction in the human male olfactory bulb.

The olfactory bulb (OB), a major structure of the limbic system, has been understudied in human investigations of psychopathologies such as depression. To explore more directly the molecular features of the OB in depression, a global comparative proteome analysis was carried out with human post-mortem OB samples from 11 males having suffered from depression and 12 healthy controls. We identified 188 differentially abundant proteins (with adjusted p < 0.

Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain.

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns.

Striatal projection neurons coexpressing dopamine D1 and D2 receptors modulate the motor function of D1- and D2-SPNs.

The role of the striatum in motor control is commonly assumed to be mediated by the two striatal efferent pathways characterized by striatal projection neurons (SPNs) expressing dopamine (DA) D1 receptors or D2 receptors (D1-SPNs and D2-SPNs, respectively), without regard to SPNs coexpressing both receptors (D1/D2-SPNs). Here we developed an approach to target these hybrid SPNs in mice and demonstrate that, although these SPNs are less abundant, they have a major role in guiding the motor function of the other two populations. D1/D2-SPNs project exclusively to the external globus pallidus and have specific electrophysiological features with distinctive integration of DA signals.

Chondroitin sulfate glycan sulfation patterns influence histochemical labeling of perineuronal nets: a comparative study of interregional distribution in human and mouse brain.

Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan (CS-GAG) side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns.

Psychiatric Comorbidities of Inflammatory Bowel Disease: It Is a Matter of Microglia's Gut Feeling.

Inflammatory bowel disease (IBD), a common term for Crohn's disease and ulcerative colitis, is a chronic, relapse-remitting condition of the gastrointestinal tract that is increasing worldwide. Psychiatric comorbidities, including depression and anxiety, are more prevalent in IBD patients than in healthy individuals. Evidence suggests that varying levels of neuroinflammation might underlie these states in IBD patients.

Persistent extrasynaptic hyperdopaminergia in the mouse hippocampus induces plasticity and recognition memory deficits reversed by the atypical antipsychotic sulpiride.

Evidence suggests that subcortical hyperdopaminergia alters cognitive function in schizophrenia and antipsychotic drugs (APD) fail at rescuing cognitive deficits in patients. In a previous study, we showed that blocking D2 dopamine receptors (D2R), a core action of APD, led to profound reshaping of mesohippocampal fibers, deficits in synaptic transmission and impairments in learning and memory in the mouse hippocampus (HP). However, it is currently unknown how excessive dopamine affects HP-related cognitive functions, and how APD would impact HP functions in such a state.

5-HT Receptor Antagonists in Neurologic and Neuropsychiatric Disorders: The Iceberg Still Lies beneath the Surface.

5-HT receptor antagonists, first introduced to the market in the mid-1980s, are proven efficient agents to counteract chemotherapy-induced emesis. Nonetheless, recent investigations have shed light on unappreciated dimensions of this class of compounds in conditions with an immunoinflammatory component as well as in neurologic and psychiatric disorders. The promising findings from multiple studies have unveiled several beneficial effects of these compounds in multiple sclerosis, stroke, Alzheimer disease, and Parkinson disease.

Oxytocin is involved in the proconvulsant effects of Sildenafil: Possible role of CREB.

Sildenafil is a phosphodiesterase type 5 inhibitor mainly used for male erectile dysfunction. One of rare yet serious adverse effects of Sildenafil is its potential to decrease seizure threshold. Ample evidence suggests that Sildenafil exerts central effects through induction of Oxytocin (OT) secretion and CREB phosphorylation.

Beyond the 5-HT3 receptors: A role for α7nACh receptors in neuroprotective aspects of tropisetron.

Accumulation of reactive oxygen species, such as hydrogen peroxide (H2O2), generated by inflammatory cells or other pathological conditions, leads to oxidative stress, which may contribute to the neuronal degeneration observed in a wide variety of neurodegenerative disorders such as Alzheimer's disease. Recent investigations have described effective properties of tropisetron, such as antiphlogistic action or protection against β-amyloid induced-neuroinflammation in rats. Our data revealed that H2O2-induced cell death in rat pheochromocytoma cell line (PC12) can be inhibited by tropisetron, as defined by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay, caspase 3 and caspase 12 levels.

Behavioral despair associated with a mouse model of Crohn's disease: Role of nitric oxide pathway.

Crohn's disease (CD) is associated with increased psychiatric co-morbidities. Nitric oxide (NO) is implicated in inflammation and tissue injury in CD, and it may also play a central role in pathogenesis of the accompanying behavioral despair. This study investigated the role of the NO pathway in behavioral despair associated with a mouse model of CD.

From Chemotherapy-Induced Emesis to Neuroprotection: Therapeutic Opportunities for 5-HT3 Receptor Antagonists.

5-HT3 receptor antagonists are extensively used as efficacious agents in counteracting chemotherapy-induced emesis. Recent investigations have shed light on other potential effects (analgesic, anxiolytic, and anti-psychotic). Some studies have reported neuroprotective properties for the 5-HT3 receptor antagonists in vitro and in vivo.

The role of serotonin in memory: interactions with neurotransmitters and downstream signaling.

Serotonin, or 5-hydroxytryptamine (5-HT), is found to be involved in many physiological or pathophysiological processes including cognitive function. Seven distinct receptors (5-HT1-7), each with several subpopulations, have been identified for serotonin, which are different in terms of localization and downstream signaling. Because of the development of selective agonists and antagonists for these receptors as well as transgenic animal models of cognitive disorders, our understanding of the role of serotonergic transmission in learning and memory has improved in recent years.

Tropisetron attenuates amyloid-beta-induced inflammatory and apoptotic responses in rats.

Background: Alzheimer's disease (AD) is a neurodegenerative disorder featured by deposition of beta-amyloid (Aβ) plaques in the hippocampus and associated cortices and progressive cognitive decline. Tropisetron, a selective 5-HT3 receptor antagonist, is conventionally used to counteract chemotherapy-induced emesis. Recent investigations describe antiphlogistic properties for tropisetron.

Medicinal chemistry of nicotinamide phosphoribosyltransferase (NAMPT) inhibitors.

Nicotinamide phoshophoribosyltransferase (NAMPT) plays a key role in the replenishment of the NAD pool in cells. This in turn makes this enzyme an important player in bioenergetics and in the regulation of NAD-using enzymes, such as PARPs and sirtuins. Furthermore, there is now ample evidence that NAMPT is secreted and has a role as a cytokine.

Estradiol reduces depressive-like behavior through inhibiting nitric oxide/cyclic GMP pathway in ovariectomized mice.

Estradiol decline has been associated with depressive-like behavior in female mice and NO has been suggested to play a major role in the pathogenesis of major depression. This study was conducted to investigate the antidepressant-like effects of acute estradiol administration in female ovariectomized (OVX) mice and the possible role of nitric oxide (NO)/cyclic GMP (cGMP) pathway. To this end, bilateral ovariectomy was performed in female mice and different doses of estradiol were injected alone or in combination with non-specific NO synthase (NOS) inhibitor (L-NAME), selective neural NOS (nNOS) inhibitor (7-NI), an NO precursor (L-arginine) or selective phosphodiesterase type 5 inhibitor (sildenafil).

Aβ leads to Ca²⁺ signaling alterations and transcriptional changes in glial cells.

The pathogenesis of Alzheimer's disease includes accumulation of toxic amyloid beta (Aβ) peptides. A recently developed cell-permeable peptide, termed Tat-Pro, disrupts the complex between synapse-associated protein 97 (SAP97) and the α-secretase a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), thereby leading to an alteration of the trafficking of the enzyme, which is important for nonamyloidogenic processing of amyloid precursor protein (APP). We report that Tat-Pro treatment, as well as the treatment with exogenous Aβ, deregulates Ca(2+) homeostasis specifically in astrocytes through increased expression of key components of Ca(2+) signaling, metabotropic glutamate receptor-5 and inositol 1,4,5-trisphosphate receptor-1.

WIN55212-2 attenuates amyloid-beta-induced neuroinflammation in rats through activation of cannabinoid receptors and PPAR-γ pathway.

Cannabinoids have been shown to exert neuroprotective effects in a plethora of neurodegenerative conditions. Over the past decade, some studies demonstrate that cannabinoids can interact with nuclear peroxisome proliferator-activated receptors (PPARs). We investigated protective properties of WIN55212-2 (WIN, a non-selective cannabinoid receptor agonist) in beta-amyloid (Aβ)-induced neurodegeneration in rat hippocampus and possible involvement of PPAR-gamma (PPAR-γ).