The aim of the present study was to explore the effects of 8-OH-DPAT, 5-HT1A receptor agonist and NAN-190, 5-HT1A receptor antagonist on anxiety-related behavior in the adult gonadectomized (GDX) male rats. Moreover, another goal of this work was to investigate whether the combination of 8-OH-DPAT or NAN-190 plus testosterone propionate (TP) could affect anxiety-like behavior more than TP alone in the adult GDX rats. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5 mg/kg, s.c.), 8-OH-DPAT (0.05 mg/kg, s.c.), NAN-190 (0.1 mg/kg, i.p.), 8-OH-DPAT in a combination with TP or NAN-190 in a combination with TP during 14 days. Experimental groups of GDX rats and control group of intact males were then tested in the elevated plus maze (EPM) and the open field test. 8-OH-DPAT treatment failed to modify anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.
Nitric oxide (NO) signalling contributes to many biological processes involved in activity-dependent fine tuning of neuronal communication. NO is involved in early developmental signalling of the nervous system and is associated with pathological pathways and age-related decline in neuronal function, thus playing a critical role in regulating neuronal function in physiology and disease. Here we assessed the effects of modulating endogenous neuronal nitric oxide synthase (NOS) activity on synaptic function, specifically on neurotransmitter release at the glutamatergic Drosophila neuromuscular junction (NMJ). We found that the absence of NOS activity enhanced synaptic release at the NMJ and conversely, overexpression of NOS diminished transmitter release. The effects of alterations in NO signalling are the consequence of acute signalling at the synapse as we did not observe any developmental changes in NMJ morphology or synaptic parameters, such as expression of the active zone protein, bruchpilot, which could account for changes in release. Ultrastructural analysis did not show any developmental effects in boutons from larvae with reduced NOS activity. Together, our data present evidence for a negative regulation of transmitter release by NO which has implications for physiological synaptic function but also pathological and age-related dysregulation of synaptic signalling.
The role of chaos in biological information processing has been established as an important breakthrough of nonlinear dynamics, after the early pioneering work of J.S. Nicolis and notably in neuroscience by the work of Walter J. Freeman and co-workers spanning more than three decades. In this work we revisit the subject and we further focus on novel results that reveal its underlying logical structure when faced with the cognition of ambiguous stimuli. We demonstrate, by utilizing a minimal model for apprehension and judgement related to Bayesian updating, that the fundamental characteristics of a biological processor obey in this case an extended, non-Boolean, logic which is characterized as a quantum logic. And we realize that in its essence the role of chaos in biological information processing accounts for, and is fully compatible with, the logic of “quantum cognition” in psychology and neuroscience.
Understanding the molecular and cellular processes that cause dementia is one of the most important challenges in neuroscience. SUMOylation is a post-translational protein modification that has been strongly implicated in neurodegenerative diseases. To investigate SUMOylation in dementia we profiled the expression of key SUMOylation pathway proteins in post mortem brain tissue from Alzheimer’s Disease (AD) and Down’s Syndrome (DS) patients. As expected, both AD and DS tissue displayed massively increased levels of phosphorylated tau compared to age- and sex-matched controls. Surprisingly, there were no changes in the levels of the E1 and E2 enzymes required for protein SUMOylation, or in levels of the deSUMOylating enzyme SENP1. There was, however, a marked decrease in the SUMO-2/3-specific deSUMOylating enzyme SENP3 in DS. There were also increased levels of SUMO-1 conjugated proteins in DS, but not in AD tissue. While these results do not exclude roles for SUMOylation in AD, they demonstrate clear differences in the profile of SUMOylation and in the expression of deSUMOylating enzymes between AD and DS brain.
Ulcerative colitis is a chronic inflammatory disease of the gastrointestinal system, affecting adults and children. Its cause is unknown, and the knowledge of reliable biomarkers is limited, especially for children. That makes the search for new biomarkers and pushing forth the analysis of the available data particularly challenging. We investigate proteomic data from children patients as a promising source, and tackle the problem implementing the recently developed parenclitic network approach to machine learning algorithms that solve classification task for proteomic data from healthy and diseased. We expect our approach to be applicable to other gastrointestinal diseases.
A spatially stable pattern of two coexisting coherent and incoherent subpopulations in nonlocally coupled dynamical systems is called as chimera states and seen in many paradigmatic limit cycle as well as chaotic models where the coupling interaction is basically diffusive type. In neuronal networks, besides diffusive electrotonic communication via gap junctions, chemical transmission occurs between the pre-synapse and post-synapse of neurons. We consider, in a numerical study, a network of neurons in a ring using the Hindmarsh-Rose (HR) bursting model for each node of the network and, apply attractive gap junctions for local coupling between the nearest neighbors and inhibitory nonlocal coupling via chemical synaptic transmission between the distant neighbors. For a range of gap junctional and chemical synaptic coupling strengths, a subpopulation of the neuronal network, in the ring, bursts asynchronously and another subpopulation remains silent in a synchronous state. The bursting subpopulation of neurons fires sequentially along the ring when the number of firing nodes remains same but change their positions periodically in time. It appears as a traveling chimera pattern in the ring when the dynamics of the individual bursting nodes is chaotic. The chimera pattern travels in a reverse direction for a larger chemical synaptic coupling strength. A purely inhibitory chemical synaptic coupling can produce a similar traveling chimera pattern, however, the dynamics of the firing nodes is then periodic.
Given the recent findings on the importance of CD38 signaling in the pathogenesis of colon cancer. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. CD38 has a genetic polymorphism, characterized by a C>G variation in the regulatory region of intron 1. The working hypothesis is that the presence of different alleles in colon cancer patients accounts for some of the clinical heterogeneity. CD38 is considered a marker of prognosis and as an indicator the activation and proliferation of cells. We hypothesized that single nucleotide polymorphisms (SNP) in the CD38 gene may be related to colon cancer risk. We evaluated one potentially functional CD38 SNP, intronic rs6449182 in two cases patients and controls. Genotyping was done using PCR-based assays in a total of 93 patients with colon cancer and 100 controls. We found that frequencies of variant allele (rs6449182 G) were significantly higher in colon cancer. Logistic regression analysis revealed an association between colon cancer and genotypes: rs6449182 CC [odds ratio (OR), 0.57; 95% confidence interval (95% CI), 0.32 – 1.01], rs6449182 CG (OR, 1.47; 95% CI, 0.83 – 2.60), and rs6449182 GG (OR, 2.26; 95% CI, 0.66 – 7.77). We observed that rs6449182 G carriers had more advanced clinical stage (P = 0.04). In conclusion, our data show that CD38 SNP may affect CD38 expression and contribute to the increased risk of colon cancer carcinogenesis.
The assembly of neural circuits during development endows the brain with the ability to perceive the environment, control motor output, and perform higher cognitive functions. Failure to assemble proper neural circuits may result in neurodevelopmental disorders including intellectual disability and autism spectrum disorders. Epigenetic mechanisms, and in particular chromatin remodeling, are potent regulators of neuronal connectivity. Here, we review recent studies highlighting the essential role of the ATPdependent nucleosomal remodeling and deacetylase (NuRD) complex in epigenetic programming of neurons to drive neural circuit assembly and organism behavior.
Isolated brain tumors contain cells that exhibit stem cell features and a tissue microenvironment bearing remarkable similarities to the normal neurogenic niche. This supports the idea that neural stem (NSCs) or progenitor cells, and their progeny are the likely tumor cell(s) of origin. This prompted the investigation of the relationship between NSCs/progenitors and the initiation of tumorigenesis. These studies led to the identification of common signaling machineries underlying NSC development and tumor formation, particularly those with known roles in proliferation and cell fate determination. This review will explore the molecular mechanisms that regulate NSC behavior in the neurogenic niche of the forebrain, and how deregulation of the developmental potential of NSCs might contribute to tumorigenesis.
Neurons adapt to stimuli through activity dependent changes to their transcriptome, a process mediated by immediate-early gene networks. Recent findings that transcriptional activation of neuronal immediate-early genes requires the formation of controlled DNA double-strand breaks (DSBs) has come as a surprise and has profound implications for neuronal function, especially in the aging brain. Here we review recent literature surrounding the phenomena of activity-dependent DNA DSBs in neurons and how this process may be exploited by transposable elements (TEs) in both naïve and aging neurons. We hypothesize the existence of Activity DEPendent Transposition (ADEPT), where neuronal excitation is able to induce genomic rearrangements through either de novo integration of TEs or by homology-directed recombination of TE-derived repetitive sequences. Epigenetic drift may cause the magnitude of ADEPT to increase with age, leading to genome instability, which we suggest presages most, if not all, neurodegenerative diseases.