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Amanda C Sharko, Jim R Fadel, Kris F Kaigler, Marlene A Wilson
Identifying the neurobiological mechanisms that underlie differential sensitivity to stress is critical for understanding the development and expression of stress-induced disorders, such as post-traumatic stress disorder (PTSD). Preclinical studies have suggested that rodents display different phenotypes associated with extinction of Pavlovian conditioned fear responses, with some rodent populations being resistant to extinction. An emerging literature also suggests a role for orexins in the consolidation processes associated with fear learning and extinction...
October 13, 2016: Physiology & Behavior
Daniel Enterría-Morales, Ivette López-López, José López-Barneo, Xavier d'Anglemont de Tassigny
Gender difference in Parkinson's disease (PD) suggests that female sex steroids may promote dopaminergic neuron survival and protect them from degeneration. The glial cell line-derived neurotrophic factor (GDNF) is believed to be dopaminotrophic; thus it is considered as a potential therapeutic target in PD. Additionally, GDNF is endogenously synthetized in the caudate/putamen of humans and striatum in rodents. A neuroprotective role of estrogens on the nigrostriatal pathway via the stimulation of GDNF has been proposed...
2016: PloS One
Aimee Chan, SiHan Li, Ahn R Lee, Joseph Leung, Alissa Yip, Jaimie Bird, Kyle E Godden, Dolores Martinez-Gonzalez, Niels C Rattenborg, Evan Balaban, Maria Pompeiano
Coordinated activity in different sets of widely-projecting neurochemical systems characterize waking (W) and sleep (S). How and when this coordination is achieved during development is not known. We used embryos and newborns of a precocial bird species (chickens) to assess developmental activation in different neurochemical systems using cFos expression, which has been extensively employed to examine cellular activation during S and W in adult mammals. Similarly to adult mammals, newborn awake chicks showed significantly higher cFos expression in W-active hypocretin/orexin (H/O), serotonergic Dorsal Raphe, noradrenergic Locus Coeruleus and cholinergic Laterodorsal and Pedunculopontine Tegmental (Ch-LDT/PT) neurons when compared to sleeping chicks...
October 4, 2016: Neuroscience
Abha K Rajbhandari, Ruoyan Zhu, Cora Adling, Michael S Fanselow, James A Waschek
Fear is an important emotional reaction in response to threatening stimuli and is important for survival. However, when fear occurs in inappropriate circumstances, it can lead to pathological conditions including an increased vulnerability for developing anxiety disorders such as posttraumatic stress disorder (PTSD). Patients with PTSD generalize fear to contexts or to environments that are not associated with the trauma. We sought to explore if increasing the level of dissimilarity relative to the context in which mice learn fear results in changes in the level of fear responding to the new context...
December 2016: Journal of Neuroscience Research
Cachétne S X Barrett, Ana C Millena, Shafiq A Khan
BACKGROUND: Activator Protein-1 (AP-1) family (cJun, JunB, JunD, cFos, FosB, Fra1, and Fra2) plays a central role in the transcriptional regulation of many genes that are associated with cell proliferation, differentiation, migration, metastasis, and survival. Many oncogenic signaling pathways converge at the AP-1 transcription complex. Transforming growth factor beta (TGF-β) is a multifunctional regulatory cytokine that regulates many aspects of cellular function, including cellular proliferation, differentiation, migration, apoptosis, adhesion, angiogenesis, immune surveillance, and survival...
September 7, 2016: Prostate
Pujarini Dutta, Atri Ta, Bhupesh Kumar Thakur, Nirmalya Dasgupta, Santasabuj Das
BACKGROUND: Chemokines play key roles in immune homeostasis and inflammatory response. Considering the role of Ccl20 and Toll-like receptor 9 (TLR9) in gut homeostasis and inflammatory bowel disease (IBD), regulation of Ccl20 by bacterial DNA, the TLR9 ligand, merits in-depth studies. METHODS: We analyzed Ccl20 expression in various epithelial cell (EC) lines by q-PCR and ELISA. In-vivo expression was investigated in isolated murine colonocytes by immunoblotting...
August 30, 2016: Biochimica et Biophysica Acta
Marc Ingenwerth, Anna Lena Reinbeck, Anna Stahr, Hans-Joachim Partke, Michael Roden, Volker Burkart, Charlotte von Gall
Circadian disruption is associated with the development of diabetes. Non-obese diabetic (NOD) mice show abnormal diurnal profiles in energy balance and locomotor activity suggesting circadian misalignment. Therefore, we analyzed cFos and mPER1 as markers for rhythmic neuronal activity within the suprachiasmatic nucleus (SCN) of wildtype (WT) and non-diabetic (nNOD) as well as acutely diabetic NOD (dNOD) mice. cFos levels show a day/night difference in both WT and nNOD but not in dNOD. mPER1 levels did not show a day/night difference in both nNOD and dNOD...
September 2, 2016: Chronobiology International
Ashley A Keiser, Lacie M Turnbull, Mara A Darian, Dana E Feldman, Iris Song, Natalie C Tronson
Anxiety disorders are commonly associated with increased generalization of fear from a stress- or trauma-associated environment to a neutral context or environment. Differences in context-associated memory in males and females may contribute to increased susceptibility to anxiety disorders in women. Here we examined sex differences in context fear generalization and its neural correlates. We observed stronger context fear conditioning and more generalization of fear to a similar context in females than males...
October 12, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Philippe Sitbon, Alain Van Elstraete, Leila Hamdi, Victor Juarez-Perez, Jean-Xavier Mazoit, Dan Benhamou, Catherine Rougeot
BACKGROUND: Opiorphin is a naturally occurring potent analgesic human peptide. It protects enkephalins from degradation and inhibits pain perception in various acute pain models via activation of endogenous opioid pathways. However, the efficacy of opiorphin continuous infusion and its chemically stable form, STR-324, in postoperative pain is unknown. METHODS: Using the Brennan model of plantar incision-induced hypersensitivity, the authors examined the postsurgical analgesic response to mechanical and thermal stimuli of 7-day continuously intravenously infused drugs (8 to 10 rats per group)...
November 2016: Anesthesiology
Karine Thibault, Sébastien Rivière, Zsolt Lenkei, Isabelle Férézou, Sophie Pezet
Chronic pain is a long-lasting debilitating condition that is particularly difficult to treat due to the lack of identified underlying mechanisms. Although several key contributing processes have been described at the level of the spinal cord, very few studies have investigated the supraspinal mechanisms underlying chronic pain. Using a combination of approaches (cortical intrinsic imaging, immunohistochemical and behavioural analysis), our study aimed to decipher the nature of functional and structural changes in a mouse model of orofacial neuropathic pain, focusing on cortical areas involved in various pain components...
2016: PloS One
Kimberly R Wiersielis, Brittany Wicks, Hannah Simko, Sarah R Cohen, Sabina Khantsis, Nausheen Baksh, David E Waxler, Debra A Bangasser
Hypersecretion of corticotropin releasing factor (CRF) is linked to the pathophysiology of major depression and post-traumatic stress disorder, disorders that are more common in women than men. Notably, preclinical studies have identified sex differences in CRF receptors that can increase neuronal sensitivity to CRF in female compared to male rodents. These cellular sex differences suggest that CRF may regulate brain circuits and behavior differently in males and females. To test this idea, we first evaluated whether there were sex differences in anxiety-related behaviors induced by the central infusion of CRF...
November 2016: Psychoneuroendocrinology
Dana M Tilley, David L Cedeño, Courtney A Kelley, Ramsin Benyamin, Ricardo Vallejo
BACKGROUND AND OBJECTIVES: Previously, we found that application of pulsed radiofrequency to a peripheral nerve injury induces changes in key genes regulating nociception concurrent with alleviation of paw sensitivity in an animal model. In the current study, we evaluated such genes after applying spinal cord stimulation (SCS) therapy. METHODS: Male Sprague-Dawley rats (n = 6 per group) were randomized into test and control groups. The spared nerve injury model was used to simulate a neuropathic pain state...
August 9, 2016: Regional Anesthesia and Pain Medicine
Mona Buhusi, Kaitlin Olsen, Benjamin Z Yang, Catalin V Buhusi
Maladaptive reactivity to stress is linked to improper decision making, impulsivity, and discounting of delayed rewards. Chronic unpredictable stress (CUS) alters dopaminergic function, re-shapes dopaminergic circuits in key areas involved in decision making, and impairs prefrontal-cortex dependent response inhibition and working memory. Glial-derived neurotrophic factor (GDNF) is essential for regulating dopamine (DA) release in the basal ganglia and for the survival of dopaminergic neurons; GDNF-deficient mice are considered an animal model for aging-related Parkinsonism...
2016: Frontiers in Behavioral Neuroscience
Gay R Holstein, Victor L Friedrich, Giorgio P Martinelli
Imidazole-4-acetic acid-ribotide (IAARP) is a putative neurotransmitter/modulator and an endogenous regulator of sympathetic drive, notably systemic blood pressure, through binding to imidazoline receptors. IAARP is present in neurons and processes throughout the CNS, but is particularly prevalent in regions that are involved in blood pressure control. The goal of this study was to determine whether IAARP is present in neurons in the caudal vestibular nuclei that participate in the vestibulo-sympathetic reflex (VSR) pathway...
October 2016: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Malek Najjar, Danish Saleh, Matija Zelic, Shoko Nogusa, Saumil Shah, Albert Tai, Joshua N Finger, Apostolos Polykratis, Peter J Gough, John Bertin, Michael J Whalen, Manolis Pasparakis, Siddharth Balachandran, Michelle Kelliher, Alexander Poltorak, Alexei Degterev
Macrophages are a crucial component of the innate immune system in sensing pathogens and promoting local and systemic inflammation. RIPK1 and RIPK3 are homologous kinases, previously linked to activation of necroptotic death. In this study, we have described roles for these kinases as master regulators of pro-inflammatory gene expression induced by lipopolysaccharide, independent of their well-documented cell death functions. In primary macrophages, this regulation was elicited in the absence of caspase-8 activity, required the adaptor molecule TRIF, and proceeded in a cell autonomous manner...
July 19, 2016: Immunity
Elizabeth J Glover, Molly J McDougle, Griffin S Siegel, Thomas C Jhou, L Judson Chandler
BACKGROUND: While the rewarding effects of alcohol contribute significantly to its addictive potential, it is becoming increasingly appreciated that alcohol's aversive properties also play an important role in the propensity to drink. Despite this, the neurobiological mechanism for alcohol's aversive actions is not well understood. The rostromedial tegmental nucleus (RMTg) was recently characterized for its involvement in aversive signaling and has been shown to encode the aversive properties of cocaine, yet its involvement in alcohol's aversive actions have not been elucidated...
August 2016: Alcoholism, Clinical and Experimental Research
Christian Reichert, Remo Perozzo, Gerrit Borchard
We present here an approach to non-covalently combine an engineered model protein with a PEGylated peptide via coiled-coil binding. To this end a fusion protein of G-CSF and the peptide sequence (JunB) was created-one sequence of JunB was expressed at the N-terminal of GCSF. JunB is able to bind to the peptide sequence cFos, which was in turn covalently linked to a chain of poly(ethylene glycol) (PEG). The selected peptide sequences are leucine zipper motives from transcription factors and are known to bind to each other specifically by formation of a super secondary structure called coiled-coil...
September 10, 2016: International Journal of Pharmaceutics
Patrycja Brzdąk, Jakub Włodarczyk, Jerzy W Mozrzymas, Tomasz Wójtowicz
Matrix metalloproteases (MMPs) comprise a family of endopeptidases that are involved in remodeling the extracellular matrix and play a critical role in learning and memory. At least 24 different MMP subtypes have been identified in the human brain, but less is known about the subtype-specific actions of MMP on neuronal plasticity. The long-term potentiation (LTP) of excitatory synaptic transmission and scaling of dendritic and somatic neuronal excitability are considered substrates of memory storage. We previously found that MMP-3 and MMP-2/9 may be differentially involved in shaping the induction and expression of excitatory postsynaptic potential (EPSP)-to-spike (E-S) potentiation in hippocampal brain slices...
June 28, 2016: Molecular Neurobiology
Julie M Butler, Karen P Maruska
Animals use multiple senses during social interactions and must integrate this information in the brain to make context-dependent behavioral decisions. For fishes, the largest group of vertebrates, the mechanosensory lateral line system provides crucial hydrodynamic information for survival behaviors, but little is known about its function in social communication. Our previous work using the African cichlid fish, Astatotilapia burtoni, provided the first empirical evidence that fish use their lateral line system to detect water movements from conspecifics for mutual assessment and behavioral choices...
2016: Frontiers in Behavioral Neuroscience
Sawako Hamasaki, Takao Mukuda, Toshiyuki Kaidoh, Masayuki Yoshida, Kazumasa Uematsu
The forebrain lamina terminalis has not yet been examined for the role of osmosensing in teleosts, although the thirst center is well known to be present in this vascular permeable forebrain region in mammals. Here, we examined vascular permeability and neuronal responsiveness to dehydration in the lamina terminalis of the mudskipper, a euryhaline goby. Evans blue and N-hydroxysulfosuccinimide-biotin both bind to blood proteins, and are impermeable to the blood-brain barrier. Intraperitoneal injection of these probes stained the walls of the preoptic recess (PR) of the third ventricle, indicating increased vascular permeability in this region...
October 2016: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
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