rudyvdbrink/CitationDatabase huggingface dataset:
Previous Early-life Stress Modifies Acute Corticosterone-induced Synaptic Plasticity in the Medial Prefrontal Cortex of Adolescent Rats.
Neuroscience, 2018

Stress can either strengthen coping strategies or enhance the risk of depression and anxiety. Synaptic plasticity is one of the key brain functions that can be affected by stress. We have previously shown that early-life stress in the form of maternal separation (MS) impairs functional synaptic plasticity in the medial prefrontal cortex (mPFC), i.e., long-term potentiation (LTP), in adolescent rats. It has been postulated that a previous experience of prolonged stress can modify the response to a subsequent acute stress challenge and influence coping strategies. Therefore, in the present study, we examined how previous MS experience influenced acute stress-induced changes in the LTP and expression of genes and proteins engaged in synaptic plasticity in the mPFC of adolescent rats. To mimic acute stress, we applied acute injections of corticosterone (CORT) and its vehicle (VEH). In control rats, acute CORT injection enhanced LTP in the mPFC. In contrast, MS rats generally exhibited an impairment of LTP that was not further affected by CORT. Moreover, for many studied parameters, such as induction of cFos and Arc mRNA and protein and activation of BDNF, GDNF and NCAM mRNA, MS rats showed diminished, vague or absent responses to acute VEH/CORT compared with those of control rats. These results suggest that previous early-life stress experiences may induce adaptive plasticity within the mPFC, which influences the response to acute stress challenge and coping strategies in adolescents. Depending on the specific environmental context, this phenomenon may lead to either future vulnerability or future resilience to stress-related psychopathologies.
Auditory and Visual Sequence Learning in Humans and Monkeys using an Artificial Grammar Learning Paradigm.
Neuroscience, 2018

Language flexibly supports the human ability to communicate using different sensory modalities, such as writing and reading in the visual modality and speaking and listening in the auditory domain. Although it has been argued that nonhuman primate communication abilities are inherently multisensory, direct behavioural comparisons between human and nonhuman primates are scant. Artificial grammar learning (AGL) tasks and statistical learning experiments can be used to emulate ordering relationships between words in a sentence. However, previous comparative work using such paradigms has primarily investigated sequence learning within a single sensory modality. We used an AGL paradigm to evaluate how humans and macaque monkeys learn and respond to identically structured sequences of either auditory or visual stimuli. In the auditory and visual experiments, we found that both species were sensitive to the ordering relationships between elements in the sequences. Moreover, the humans and monkeys produced largely similar response patterns to the visual and auditory sequences, indicating that the sequences are processed in comparable ways across the sensory modalities. These results provide evidence that human sequence processing abilities stem from an evolutionarily conserved capacity that appears to operate comparably across the sensory modalities in both human and nonhuman primates. The findings set the stage for future neurobiological studies to investigate the multisensory nature of these sequencing operations in nonhuman primates and how they compare to related processes in humans.
Sickness behaviour after lipopolysaccharide treatment in ghrelin deficient mice.
Brain, behavior, and immunity, 2014

Ghrelin is an orexigenic hormone produced mainly by the gastrointestinal system and the brain. Much evidence also indicates a role for ghrelin in sleep and thermoregulation. Further, ghrelin was recently implicated in immune system modulation. Administration of bacterial lipopolysaccharide (LPS) induces fever, anorexia, and increased non-rapid-eye movement sleep (NREMS) and these actions are mediated primarily by proinflammatory cytokines. Ghrelin reduces LPS-induced fever, suppresses circulating levels of proinflammatory cytokines and reduces the severity and mortality of various models of experimental endotoxemia. In the present study, we determined the role of intact ghrelin signaling in LPS-induced sleep, feeding, and thermoregulatory responses in mice. Sleep-wake activity was determined after intraperitoneal, dark onset administration of 0.4, 2 and 10 μg LPS in preproghrelin knockout (KO) and wild-type (WT) mice. In addition, body temperature, motor activity and changes in 24-h food intake and body weight were measured. LPS induced dose-dependent increases in NREMS, and suppressed rapid-eye movement sleep, electroencephalographic slow-wave activity, motor activity, food intake and body weight in both Ppg KO and WT mice. Body temperature changes showed a biphasic pattern with a decrease during the dark period followed by an increase in the light phase. The effects of the low and middle doses of LPS were indistinguishable between the two genotypes. Administration of 10 μg LPS, however, induced significantly larger changes in NREMS and wakefulness amounts, body temperature, food intake and body weight in the Ppg KO mice. These findings support a role for ghrelin as an endogenous modulator of inflammatory responses and a central component of arousal and feeding circuits.
Anatomical correlates of recovery in single pellet reaching in spinal cord injured rats.
Experimental neurology, 2013

Modeling spinal cord injury (SCI) in animals is challenging because an appropriate combination of lesion location, lesion severity and behavioral testing is essential to analyze recovery of motor function. For particular tests such as single pellet reaching, the contribution of individual descending tracts to recovery has been investigated using specific tract ablation or graded lesions. However, it has not been established whether single pellet reaching is sufficiently sensitive for assessing the efficacy of treatments for cervical SCI (e.g., one of the currently most successful treatment approaches: rehabilitative training). To address this issue, we trained adult rats in single pellet reaching before and after a cervical (C4) spinal lesion. Animals with lesions of increasing severity were grouped into categories based on damage to anatomical structures such as the corticospinal tract (CST) and the rubrospinal tract (RST), two descending motor tracts that have been implicated in fine motor control of the forelimb. We related lesion extent to spontaneous recovery and plasticity-promoting post injury training and found that reaching performance was not correlated with lesion size or the extent of CST or RST injury. Interestingly, the dorsolateral quadrant (DLQ) lesion category, in which the unilateral dorsal CST and most of the unilateral RST are lesioned, was the only category that showed a clear effect of plasticity-promoting treatment (i.e., training), indicating its usefulness as a lesion model for this testing paradigm. The DLQ lesion likely strikes a balance between tissue sparing and functional impairment and is, therefore, best suited to maximize the potential to observe treatment effects of plasticity-promoting treatments using single pellet reaching. Because of the specific lesion size that is necessary to observe treatment effects, the single pellet skilled reaching task can be considered a stringent behavioral test and therefore may be useful for predicting translational success of potential treatments. However, due to the variability in the success rate, the labor-intensive nature, and the limited usefulness to test functional outcome of a wide range of lesion severities, we are hesitant to continue to use single pellet reaching to assess the effectiveness of currently available treatments for cervical SCI.
Neonatal colonic inflammation sensitizes voltage-gated Na(+) channels via upregulation of cystathionine β-synthetase expression in rat primary sensory neurons.
American journal of physiology. Gastrointestinal and liver physiology, 2013

The pathogenesis of pain in irritable bowel syndrome (IBS) is poorly understood, and treatment remains difficult. We have previously reported that colon-specific dorsal root ganglion (DRG) neurons were hyperactive in a rat model of IBS induced by neonatal colonic inflammation (NCI). This study was designed to examine plasticity of voltage-gated Na(+) channel activities and roles for the endogenous hydrogen sulfide-producing enzyme cystathionine β-synthetase (CBS) in chronic visceral hyperalgesia. Abdominal withdrawal reflex (AWR) scores were recorded in response to graded colorectal distention in adult male rats as a measure of visceral hypersensitivity. Colon-specific DRG neurons were labeled with 1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate and acutely dissociated for measuring Na(+) channel currents. Western blot analysis was employed to detect changes in expressions of voltage-gated Na(+) (Na(V)) channel subtype 1.7, Na(V)1.8, and CBS. NCI significantly increased AWR scores when compared with age-matched controls. NCI also led to an ~2.5-fold increase in Na(+) current density in colon-specific DRG neurons. Furthermore, NCI dramatically enhanced expression of Na(V)1.7, Na(V)1.8, and CBS in colon-related DRGs. CBS was colocalized with Na(V)1.7 or -1.8 in colon-specific DRG neurons. Administration of O-(carboxymethyl)hydroxylamine hemihydrochloride (AOAA), an inhibitor for CBS, remarkably suppressed Na(+) current density and reduced expression of Na(V)1.7 and Na(V)1.8. More importantly, intraperitoneal or intrathecal application of AOAA attenuated AWR scores in NCI rats in a dose-dependent manner. These data suggest that NCI enhances Na(+) channel activity of colon DRG neurons, which is most likely mediated by upregulation of CBS expression, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.
STochastic Optical Reconstruction Microscopy (STORM) reveals the nanoscale organization of pathological aggregates in human brain.
Neuropathology and applied neurobiology, 2021

Histological analysis of brain tissue samples provides valuable information about the pathological processes leading to common neurodegenerative disorders. In this context, the development of novel high-resolution imaging approaches is a current challenge in neuroscience.
Dual role of mitochondria in producing melatonin and driving GPCR signaling to block cytochrome c release.
Proceedings of the National Academy of Sciences of the United States of America, 2017

G protein-coupled receptors (GPCRs) are classically characterized as cell-surface receptors transmitting extracellular signals into cells. Here we show that central components of a GPCR signaling system comprised of the melatonin type 1 receptor (MT
Orexin microinjection in the medullary raphe increases heart rate and arterial pressure but does not reduce tail skin blood flow in the awake rat.
Neuroscience, 2012

The rostral medullary raphe region is an important target of hypothalamic orexin neurons; however, little is known of the effect of orexin in this key autonomic and somatic premotor region. Here we tested the effect of orexin-A (3 and 30 pmol) microinjected in the medullary raphe, on heart rate (HR), mean arterial pressure (MAP), tail skin blood flow, body temperature, and behavior in freely moving, awake rats. HR, MAP, and body activity were recorded by radio-telemetry. Changes in tail skin blood flow and body temperature, as well as potential interscapular brown adipose tissue thermogenesis were recorded indirectly by infrared thermography of the skin of the tail, lumbosacral back, and interscapular back areas, respectively. Compared with saline, orexin-A (30 pmol) evoked significant and long lasting increases in HR (+99 bpm), MAP (+11 mmHg), and body activity (grooming, not locomotor activity). However, it did not reduce tail skin blood flow more than saline, and there was no significant increase in body temperature. A small, though significant, thermogenic effect was observed in the interscapular region, but this effect is more likely to have originated from activity in neck and shoulder muscles than brown adipose tissue. Thus, orexin projections to the rostral medullary raphe can mediate significant cardiovascular changes, but does not seem to affect tail skin vasomotor tone or brown adipose tissue in the awake rat. This important brainstem relay may contribute to the cardiovascular changes evoked by arousal and various forms of stress that are associated with activation of orexin neurons.
Is social jetlag similar to travel-induced jetlag? Results of a validation study.
Chronobiology international, 2020

Social jetlag (SJL) is defined as the misalignment between the biological clocks and the social clock imposed by work and social constraints. In order to accomplish the workdays duties, people tend to not respect the internally sleep-wake cycle during the week, often using alarm clock to wake-up, which would lead to a chronic form of travel-induced jetlag. This circadian misalignment has been found to be associated with increased health risk and health-impairing behaviors. In this cross-sectional study, we aimed to explore whether the SJL is a valid concept for the travel-induced jetlag symptoms, as well as what is the cutoff point with best parameters for defining the presence of SJL, in a sample of undergraduate students of a university in Southern Brazil. We assessed SJL by the Munich ChronoType Questionnaire (MCTQ) and defined the concept as the difference between the midsleep point on free days and the midsleep point on classes days. The gold standard was defined as having at least one travel-induced jetlag symptom (fatigue, sleepiness or difficulty concentrating). Relative SJL, sensitivity and specificity were calculated for different cutoff points, plotted on ROC curves. A total of 452 students with complete sleep information were included in the analysis. The relative SJL mean was 2 h 23 min (SD = 1 h 24 min; range -3 h to 7 h 58 min) and 63.7% of the students had ≥2 h of relative SJL. All the tested cutoff points of the instrument had low sensitivity and specificity values, covering a small area under the ROC curve (0.487). The best parameters were for the cutoff point ≥2 h, with 63.4% sensitivity and 35.9% specificity. SJL did not revealed to be a valid concept for the studied sample comparing it to travel-induced jetlag symptomatology. One possible explanation for the lack of validity of our results regards the fact that SJL may not have the same apparent wide-term effects as the travel-induced jetlag. Then, the symptoms of SJL do not well represent the symptoms of travel-induced jetlag.
NCB5OR Deficiency in the Cerebellum and Midbrain Leads to Dehydration and Alterations in Thirst Response, Fasted Feeding Behavior, and Voluntary Exercise in Mice.
Cerebellum (London, England), 2018

Cytosolic NADH-cytochrome-b5-oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues. We have previously reported that global ablation of NCB5OR in mice results in early-onset lean diabetes with decreased serum leptin levels and increased metabolic and feeding activities. The conditional deletion of NCB5OR in the mouse cerebellum and midbrain (conditional knock out, CKO mice) results in local iron dyshomeostasis and altered locomotor activity. It has been established that lesion to or removal of the cerebellum leads to changes in nutrient organization, visceral response, feeding behavior, and body weight. This study assessed whether loss of NCB5OR in the cerebellum and midbrain altered feeding or metabolic activity and had an effect on serum T3, cortisol, prolactin, and leptin levels. Metabolic cage data revealed that 16 week old male CKO mice had elevated respiratory quotients and decreased respiratory water expulsion, decreased voluntary exercise, and altered feeding and drinking behavior compared to wild-type littermate controls. Most notably, male CKO mice displayed higher consumption of food during refeeding after a 48-h fast. Echo MRI revealed normal body composition but decreased total water content and hydration ratios in CKO mice. Increased serum osmolality measurements confirmed the dehydration status of male CKO mice. Serum leptin levels were significantly elevated in male CKO mice while prolactin, T3, and cortisol levels remain unchanged relative to wild-type controls, consistent with elevated transcript levels for leptin receptors (short form) in the male CKO mouse cerebellum. Taken together, these findings suggest altered feeding response post starvation as a result of NCB5OR deficiency in the cerebellum.
A direct examination of the cognitive underpinnings of multitasking abilities: A first study examining schizophrenia.
Psychiatry research, 2018

Many real world activities are complex and require multitasking abilities. However, the nature of these abilities remains poorly understood, and in particular in schizophrenia. The aim of the present study was to provide a better understanding of such abilities with the help of a newly developed computerized tool, the Computerized Meeting Preparation Task (CMPT). Fifty-seven individuals with schizophrenia and 39 healthy controls completed the CMPT and an extensive cognitive battery. Patients were also evaluated with a series of clinical measures. During the CMPT, participants are asked to prepare a room for a meeting while, at the same time, dealing with interruptions, solving problems, and remembering prospective memory instructions. The CMPT was found to significantly differentiate patients and healthy controls for several variables. Results also showed that multitasking abilities were related to a large array of cognitive functions and, in particular, to those associated to executive functioning. These relations were not explained by the presence of a general cognitive impairment. Finally, a double dissociation between multitasking abilities and performance on standard cognitive tests was observed. Altogether, these results underline the importance of evaluating multitasking abilities in schizophrenia as it allows detecting cognitive difficulties that cannot be identified by standard cognitive tests.
Interaction between steady-state visually evoked potentials at nearby flicker frequencies.
Scientific reports, 2020

Steady-state visually evoked potential (SSVEP) studies routinely employ simultaneous presentation of two temporally modulated stimuli, with SSVEP amplitude modulations serving to index top-down cognitive processes. However, the nature of SSVEP amplitude modulations as a function of competing temporal frequency (TF) has not been systematically studied, especially in relation to the normalization framework which has been extensively used to explain visual responses to multiple stimuli. We recorded spikes and local field potential (LFP) from the primary visual cortex (V1) as well as EEG from two awake macaque monkeys while they passively fixated plaid stimuli with components counterphasing at different TFs. We observed asymmetric SSVEP response suppression by competing TFs (greater suppression for lower TFs), which further depended on the relative orientations of plaid components. A tuned normalization model, adapted to SSVEP responses, provided a good account of the suppression. Our results provide new insights into processing of temporally modulated visual stimuli.
Preventing suicide and homicide in the United States: the potential benefit in human lives.
Psychiatry research, 2009

In order to assess the potential benefit in human lives if all geographical regions in the US (Northeast, South, Midwest, and West) achieved the lowest suicide and homicide rates observed within these regions, age-, race- and gender-adjusted suicide and homicide rates for each of the four regions were calculated based on data retrieved using the Centers for Disease Control and Prevention database for 1999-2004. Data on known risk factors were retrieved from online sources. Overall suicide rates (10.42 per 100,000) exceeded homicide rates (6.97 per 100,000). Almost 27% (12,942 lives per year) of the 288,222 suicide and homicide deaths during the study period might have been avoided if all US regions achieved the mortality rate reported by the Northeast. A firearm was used in 55% of all suicides and 66% of all homicides. In the total estimate of avoidable deaths, firearm suicides (90%) and firearm homicides (75%) were overrepresented. The Northeast had the lowest access to firearms (20%) contrasted to almost double in the other regions, whereas greater firearms availability was related to unrestricted firearm legislation. Measures to restrict firearms availability should be highly prioritized in the public health agenda in order to achieve an impressive benefit in human lives.
The reduction of intraepidermal P2X
The Journal of comparative neurology, 2017

Skin biopsies from patients with neuropathic pain often show changes in epidermal innervation, although it remains to be elucidated to what extent such changes can be linked to a particular subgroup of nerve fibers and how these changes are correlated with pain intensity. Here, we investigated to what extent behavioral signs of hyperalgesia are correlated with immunohistochemical changes of peptidergic and non-peptidergic epidermal nerve fibers in a rat model of nerve injury-induced pain. Rats subjected to unilateral partial ligation of the sciatic nerve developed significant mechanical and thermal hyperalgesia as tested by the withdrawal responses of the ipsilateral footpad to von Frey hairs and hotplate stimulation. At day 14, epidermal nerve fiber density and total epidermal nerve fiber length/mm
Nucleus accumbens high-frequency stimulation selectively impacts nigrostriatal dopaminergic neurons.
The international journal of neuropsychopharmacology, 2014

High-frequency stimulation of the nucleus accumbens, also known as deep brain stimulation (DBS), is currently used to alleviate obsessive compulsive symptoms when pharmacotherapy is ineffective. However, the mechanism by which DBS achieves its therapeutic actions is not understood. Imaging studies and the actions of dopaminergic drugs in untreated patients suggest that the dopamine (DA) system likely plays a role in the pathophysiology of obsessive compulsive disorder. Therefore, we examined whether DBS would impact the DA system as a potential component of its therapeutic actions. The activity of DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) were recorded in anesthetized rats under high-frequency stimulation. DA neuron activity was measured in terms of number of neurons firing, average firing rate and firing pattern. DBS of the nucleus accumbens core did not significantly affect VTA activity or discharge pattern. On the other hand, DBS caused a potent decrease in the number of SNc DA neurons firing spontaneously. Such an effect could contribute to the disruption of pathological habit formation in the SNc-dorsal striatal projection system that may have therapeutic implications for the treatment of obsessive compulsive disorder.