rudyvdbrink/CitationDatabase huggingface dataset:
Micro-opioid receptor activation in the basolateral amygdala mediates the learning of increases but not decreases in the incentive value of a food reward.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

The decision to perform, or not perform, actions known to lead to a rewarding outcome is strongly influenced by the current incentive value of the reward. Incentive value is largely determined by the affective experience derived during previous consumption of the reward-the process of incentive learning. We trained rats on a two-lever, seeking-taking chain paradigm for sucrose reward, in which responding on the initial seeking lever of the chain was demonstrably controlled by the incentive value of the reward. We found that infusion of the μ-opioid receptor antagonist, CTOP (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH(2)), into the basolateral amygdala (BLA) during posttraining, noncontingent consumption of sucrose in a novel elevated-hunger state (a positive incentive learning opportunity) blocked the encoding of incentive value information normally used to increase subsequent sucrose-seeking responses. Similar treatment with δ [N, N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864)] or κ [5'-guanidinonaltrindole (GNTI)] antagonists was without effect. Interestingly, none of these drugs affected the ability of the rats to encode a decrease in incentive value resulting from experiencing the sucrose in a novel reduced-hunger state. However, the μ agonist, DAMGO ([d-Ala2, NMe-Phe4, Gly5-ol]-enkephalin), appeared to attenuate this negative incentive learning. These data suggest that upshifts and downshifts in endogenous opioid transmission in the BLA mediate the encoding of positive and negative shifts in incentive value, respectively, through actions at μ-opioid receptors, and provide insight into a mechanism through which opiates may elicit inappropriate desire resulting in their continued intake in the face of diminishing affective experience.
Ischemic regulation of brain-derived neurotrophic factor-mediated cell volume and TrkB expression in glial (Müller) and bipolar cells of the rat retina.
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 2016

Osmotic swelling of neurons and glial cells contributes to retinal edema and neurodegeneration. BDNF, a major neuroprotectant in the retina, was shown to inhibit osmotic swelling of glial (Müller) and bipolar cells in the rat retina; the effect of BDNF on the bipolar cell swelling is mediated by inducing a release of neuroprotective cytokines from Müller cells (Berk et al., Neuroscience 295:175-186, 2015). We determined whether BDNF-mediated cell volume regulation was altered after transient retinal ischemia.
Integrating HIV prevention into services for abused women in South Africa.
AIDS and behavior, 2010

The relationship between intimate partner violence (IPV) and HIV risk is well documented, but few interventions jointly address these problems. We developed and examined the feasibility of an intervention to reduce HIV risk behaviors among 97 women seeking services for IPV from a community-based NGO in Johannesburg, South Africa. Two versions of the intervention (a 6-session group and a 1-day workshop) were implemented, both focusing on HIV prevention strategies integrated with issues of gender and power imbalance. Attendance was excellent in both intervention groups. Assessments were conducted at baseline, post-intervention and two-month follow-up to demonstrate the feasibility of an intervention trial. Women in both groups reported reductions in HIV misperceptions and trauma symptoms, and increases in HIV knowledge, risk reduction intentions, and condom use self-efficacy. The 6-session group showed greater improvements in HIV knowledge and decreases in HIV misperceptions in comparison to the 1-day workshop. The study demonstrated the feasibility and potential benefit of providing HIV prevention intervention to women seeking assistance for IPV.
Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.
Journal of pineal research, 2015

Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity.
Remodeling of lipid bodies by docosahexaenoic acid in activated microglial cells.
Journal of neuroinflammation, 2016

Organelle remodeling processes are evolutionarily conserved and involved in cell functions during development, aging, and cell death. Some endogenous and exogenous molecules can modulate these processes. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, has mainly been considered as a modulator of plasma membrane fluidity in brain development and aging, while DHA's role in organelle remodeling in specific neural cell types at the ultrastructural level remains largely unexplored. DHA is notably incorporated into dynamic organelles named lipid bodies (LBs). We hypothesized that DHA could attenuate the inflammatory response in lipopolysaccharide (LPS)-activated microglia by remodeling LBs and altering their functional interplay with mitochondria and other associated organelles.
How does testosterone act to regulate a multifaceted adaptive response? Lessons from studies of the avian song system.
Journal of neuroendocrinology, 2020

In male songbirds, song functions to attract a mate or to defend a territory; it is therefore often produced in the context of reproduction. Testosterone of gonadal origin increases during the reproductive phase of the annual cycle and significantly enhances song production, as well as song development, via effects on song crystallisation. The neural control of birdsong production and learning is highly modular. We implanted testosterone or androgen antagonists into specific brain regions or in the periphery of castrated male canaries and, in this way, identified how androgen signalling in specific locations regulates a variety of birdsong features. For example, castrated male canaries treated with testosterone in the preoptic area only and exposed to long days sing at high rates compared to castrated male canaries not treated with testosterone. However, these birds with testosterone in the preoptic area still produce songs with substantially lower song stereotypy and amplitude; these features are controlled by testosterone acting in the song control nuclei HVC and robust nucleus of the arcopallium. Specific aspects of the learned singing behaviour are thus regulated by androgens acting at multiple levels in the brain in a non-redundant fashion. The action of testosterone in the preoptic area is related to the hormonal regulation of the motivation to sing but not to various aspects of song performance. Multiple aspects of song quality are instead precisely regulated by steroids acting in distinct song control nuclei. Females exert a strong choice for specific features of male song in canaries and this choice is influenced by the endocrine state of the female. The female song system is also involved in song production, as well as song perception, although the specificity of this hormone action has not yet been investigated.
A single exposure to alcohol during brain development induces microencephaly and neuronal losses in genetically susceptible mice, but not in wild type mice.
Neurotoxicology, 2009

Maternal alcohol abuse during pregnancy can damage the fetal brain and lead to fetal alcohol syndrome (FAS). Despite public warnings discouraging alcohol use during pregnancy, many pregnant women continue to drink intermittently because they do not believe that occasional exposures to alcohol can be harmful to a fetus. However, because of genetic differences, some fetuses are much more susceptible than others to alcohol-induced brain injury. Thus, a relatively low quantity of alcohol that may be innocuous to most fetuses could damage a genetically susceptible fetus. Neuronal nitric oxide synthase (nNOS) can protect developing mouse neurons against alcohol toxicity by synthesizing neuroprotective nitric oxide. This study examined whether a single exposure to alcohol, which causes no evident injury in wild type mice, can damage the brains of mice genetically deficient for nNOS (nNOS-/- mice). Wild type and nNOS-/- mice received intraperitoneal injections of alcohol (0.0, 2.2, or 4.4mg/g body weight) either as a single dose on postnatal day (PD) 4 or as repeated daily doses over PD4-9. Brain volumes and neuronal numbers within the hippocampus and cerebral cortex were determined on PD10. Alcohol exposure on PD4-9 restricted brain growth and caused neuronal death in both strains of mice, but the severity of microencephaly and neuronal loss were more severe in the nNOS-/- mice than in wild type. The 4.4 mg/g alcohol dose administered on PD4 alone caused significant neuronal loss and microencephaly in the nNOS-/- mice, while this same dose caused no evident injury in the wild type mice. Thus, during development, a single exposure to alcohol can injure a genetically vulnerable brain, while it leaves a wild type brain unaffected. Since the genes that confer alcohol resistance and vulnerability in developing humans are unknown, any particular human fetus is potentially vulnerable. Thus, women should be counseled to consume no alcohol during pregnancy.
Dopamine effects on human error processing depend on catechol-O-methyltransferase VAL158MET genotype.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011

Brain dopamine (DA) has been linked to error processing. Because high and low (vs medium) prefrontal cortex (PFC) DA levels may facilitate D2-receptor-related modulations of PFC neural activation patterns, we hypothesized that high and low DA predicts increased error-specific transitions of PFC activity. Male human participants (n = 169) were genotyped for the catechol-O-methyltransferase (COMT) Val158Met polymorphism, associated with low (Val) and medium (Met) PFC DA levels. In addition, DRD2TaqIa and 5-HTTLPR, associated with striatal D(2) receptor density and serotonin uptake, respectively, were assessed. Participants received placebo or a selective DA-D(2) receptor blocker (sulpiride, 200 mg) and performed a Flanker task. EEG was recorded and decomposed into independent brain components (ICs) using independent component analysis. After errors, participants displayed (1) a negative deflection in ICs source-localized to the proximity of the anterior midcingulate cortex [IC-error-related negativity (IC-ERN)], (2) increased midcingulate cortex IC power in the delta/theta frequency range, and (3) slowing in the subsequent trial [posterror slowing (PES)]. Importantly, all, IC-ERN, delta/theta power, and PES were modulated by COMT × Substance interactions such that the Val allele predicted elevated IC-ERN, delta/theta power, and PES after placebo; this association was reversed under sulpiride. Because low doses of sulpiride presumably increase PFC DA levels, the COMT × Substance interaction supports the hypothesis that low (Val, placebo) and high (Met, sulpiride) versus medium (Val, sulpiride; Met, placebo) DA levels elevate reactivity to errors. Consistent with an influence of serotonin on PFC DA, the COMT × Substance interaction was modulated by 5-HTTLPR.
Neurotropin(®) ameliorates chronic pain via induction of brain-derived neurotrophic factor.
Cellular and molecular neurobiology, 2015

Neurotropin (NTP)(®), a non-protein extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, is used clinically for the treatment of neuropathic pain. Moreover, NTP may activate the descending pain inhibitory system. Depression-like behavior is often complicated by chronic pain. However, little is known about NTP-mediated prevention of mood disorders in chronic pain and its molecular mechanisms. We aimed to investigate the effects of NTP on brain-derived neurotrophic factor (BDNF)-mediated signaling and gene expression in chronic pain. In addition, these effects of NTP were compared with pregabalin which is an anticonvulsant, anxiolytic analgesic used to treat neuropathic pain and fibromyalgia. A chronic constriction injury model was established in Sprague-Dawley rats. The pain response was assessed using a paw withdrawal latency (PWL) test and depression was assessed by the immobility time in a forced swim test (FST). NTP was orally administered in two doses of 50 NU (Neurotropin Unit) and 100 NU/kg for 7 days from day 7 after injury. To measure the analgesic and anti-depressant effects of NTP, either K252a (a tyrosine kinase inhibitor), or 5,7-dihydroxy tryptamine (5,7-DHT, a selective toxin for 5-HTergic neurons) was administered by intracerebroventricular injection. Changes in pERK1/2 and pCREB (immunohistochemistry), 5-HT, and BDNF protein level (ELISA) and BDNF mRNA (RT-PCR) were measured in the anterior cingulate cortex (ACC) and in the rostral ventromedial medulla (RVM) 14 days after injury. After injury, the rats showed a decrease in PWL associated with the increase in time of immobility in FST. In this injury model, NTP blocked both the decrease in PWL and the increase in the FST, while pregabalin (10 mg/kg, po.) did not affect the increase in the FST. These effects of NTP were reversed by K252a, and 5,7-DHT. The analgesic effects of pregabalin were not reversed by K252a. NTP normalized the injury-induced excessive activation of pERK1/2 associated with decreased pCREB and BDNF mRNA in the ACC and in the RVM, and these changes were reversed by 5,7-DHT. In contrast, pregabalin did not affect either pCREB or BDNF levels in the chronic pain model. NTP ameliorated chronic pain and pain-related depression by normalizing the induction of BDNF associated with the 5-HTergic system. Pregabalin showed the analgesic effects but had no effects on either depression or the BDNF pathway. These results suggest that NTP may represent an additional drug strategy for chronic pain associated with depression.
Ovarian steroids increase spinogenetic proteins in the macaque dorsal raphe.
Neuroscience, 2012

Dendritic spines are the basic structural units of neuronal plasticity. Intracellular signaling cascades that promote spinogenesis have centered on RhoGTPases. We found that ovarian steroids increase gene expression of RhoGTPases [Ras homolog gene family member A (RhoA), cell division control protein 42 homolog (Cdc42), and ras-related C3 botulinum toxin substrate (Rac)] in laser-captured serotonin neurons. We sought to confirm that the increases observed in gene expression translate to the protein level. In addition, a preliminary study was conducted to determine whether an increase in spines occurs via detection of the spine marker protein, postsynaptic density-95 (PSD-95). Adult ovariectomized (Ovx) monkeys were treated with estradiol (E), progesterone (P), or E+P for 1 month. Sections through the dorsal raphe nucleus were immunostained for RhoA and Cdc42 (n=3-4/group). The number and positive pixel area of RhoA-positive cells and the positive pixel area of Cdc42-positive fibers were determined. On combining E- and E+P-treated groups, there was a significant increase in the average and total cell number and positive pixel area of RhoA-positive cells. E, P, and E+P treatments, individually or combined, also increased the average and total positive pixel area of Cdc42-positive fibers. With remaining sections from two animals in each group, we conducted a preliminary examination of the regulation of PSD-95 protein expression. PSD-95, a postsynaptic scaffold protein, was examined with immunogold silver staining (n=2/group), and the total number of PSD-95-positive puncta was determined with stereology across four levels of the dorsal raphe. E, P, and E+P treatment significantly increased the total number of PSD-95-positive puncta. Together, these findings indicate that ovarian steroids act to increase gene and protein expression of two pivotal RhoGTPases involved in spinogenesis and preliminarily indicate that an increased number of spines and/or synapses result from this action. Increased spinogenesis on serotonin dendrites would facilitate excitatory glutamatergic input and in turn, increase serotonin neuronal activity throughout the brain.
Investigation of Slow-wave Activity Saturation during Surgical Anesthesia Reveals a Signature of Neural Inertia in Humans.
Anesthesiology, 2017

Previously, we showed experimentally that saturation of slow-wave activity provides a potentially individualized neurophysiologic endpoint for perception loss during anesthesia. Furthermore, it is clear that induction and emergence from anesthesia are not symmetrically reversible processes. The observed hysteresis is potentially underpinned by a neural inertia mechanism as proposed in animal studies.
Are there causal relationships between attention-deficit/hyperactivity disorder and body mass index? Evidence from multiple genetically informed designs.
International journal of epidemiology, 2021

Attention-deficit/hyperactivity disorder (ADHD) and body mass index (BMI) are associated. However, it remains unclear whether this association reflects causal relationships in either direction or confounding. Here, we implemented genetically informed methods to examine bidirectional causality and potential confounding.
Fibromyalgia is associated with decreased connectivity between pain- and sensorimotor brain areas.
Brain connectivity, 2014

Fibromyalgia (FM) is a syndrome characterized by chronic pain without known peripheral causes. Previously, we have reported dysfunctional pain inhibitory mechanisms for FM patients during pain administration. In this study we employed a seed correlation analysis, independent component analysis (ICA), and an analysis of fractional amplitude of low frequency fluctuations (fALFF) to study differences between a cohort of female FM patients and an age- and sex-matched healthy control group during a resting-state condition. FM patients showed decreased connectivity between thalamus and premotor areas, between the right insula and primary sensorimotor areas, and between supramarginal and prefrontal areas. Individual sensitivity to painful pressure was associated with increased connectivity between pain-related regions (e.g., insula and thalamus) and midline regions of the default mode network (including posterior cingulate cortex and medial prefrontal cortex) among patients and controls. However, neither ICA nor fALFF revealed any group differences. Our findings suggest that abnormal connectivity patterns between pain-related regions and the remaining brain during rest reflect an impaired central mechanism of pain modulation in FM. Weaker coupling between pain regions and prefrontal- and sensorimotor areas might indicate a less efficient system level control of pain circuits. Moreover, our results show that multiple, complementary analytical approaches are valuable for obtaining a more comprehensive characterization of deviant resting-state activity. In conclusion, our findings show that FM primarily is associated with decreased connectivity, for example, between several pain-related areas and sensorimotor regions, which could reflect a deficiency in pain regulation.
Eye pain in the white and quiet eye.
Current opinion in ophthalmology, 2020

Eye pain is one of the most common presenting symptoms in ophthalmology. It can range from bothersome to debilitating for patients, and it can be vexing for clinicians, especially in the white and quiet eye. The purpose of this review is to provide updates of recent literature regarding eye pain and to communicate our current understanding regarding the evaluation and management of conditions that cause eye pain with a relatively normal examination.
Lipid biochemical changes detected in normal appearing white matter of chronic multiple sclerosis by spectral coherent Raman imaging.
Chemical science, 2018

Multiple sclerosis (MS) exhibits demyelination, inflammatory infiltration, axonal degeneration, and gliosis, affecting widespread regions of the central nervous system (CNS). While white matter MS lesions have been well characterized pathologically, evidence indicates that the MS brain may be globally altered, with subtle abnormalities found in grossly normal appearing white matter (NAWM). These subtle changes are difficult to investigate by common methods such as histochemical stains and conventional magnetic resonance imaging. Thus, the prototypical inflammatory lesion likely represents the most obvious manifestation of a more widespread involvement of the CNS. We describe the application of spectral coherent anti-Stokes Raman Scattering (sCARS) microscopy to study such changes in chronic MS tissue particularly in NAWM. Subtle changes in myelin lipid biochemical signatures and intra-molecular disorder of fatty acid acyl chains of otherwise normal-appearing myelin were detected, supporting the notion that the biochemical involvement of the MS brain is far more extensive than conventional methods would suggest.
Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β-amyloid.
Annals of neurology, 2013

We examined agreement and disagreement between 2 biomarkers of β-amyloid (Aβ) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] Aβ1-42 ) in normal aging and dementia in a large multicenter study.