rudyvdbrink/CitationDatabase huggingface dataset:
Improved outcome after peripheral nerve injury in mice with increased levels of endogenous ω-3 polyunsaturated fatty acids.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012

Functional recovery after a peripheral nerve injury (PNI) is often poor. There is a need for therapies that protect neurons against injury and enhance regeneration. ω-3 polyunsaturated fatty acids (PUFAs) have been shown to have therapeutic potential in a variety of neurological disorders, including acute traumatic injury. The objective of this study was to assess the neuroprotective and pro-regenerative potential of ω-3 PUFAs in PNI. We investigated this in mice that express the fat-1 gene encoding for ω-3 fatty acid desaturase, which leads to an increase in endogenous ω-3 PUFAs and a concomitant decrease in ω-6 PUFAs. Dorsal root ganglion (DRG) neurons from wild-type or fat-1 mice were subjected to a mechanical strain or hypoxic injury, and cell death was assessed using ethidium homodimer-1 labeling. The fat-1 background appears to confer robust neuroprotection against both injuries. We then examined the early functional and morphological changes in wild-type and fat-1 mice after a sciatic nerve crush. An accelerated functional recovery 7 d after injury was seen in fat-1 mice when assessed using von Frey filaments and the sciatic nerve functional index. These observations were also mapped to changes in injury-related markers. The injury-induced expression of ATF-3 was decreased in the DRG of fat-1 mice, whereas the axons detected 6 mm distal to the crush were increased. Fat-1 animals also had some protection against muscle atrophy after injury. In conclusion, both in vitro and in vivo experiments support the idea that a higher endogenous ω-3 PUFA could lead to beneficial effects after a PNI.
Alexithymia and its relationships with C-reactive protein and serum lipid levels among drug naïve adult outpatients with major depression.
Progress in neuro-psychopharmacology & biological psychiatry, 2008

Several studies have investigated the relationship between C-reactive protein (CRP) and serum lipid levels in Major Depression (MD), but no study has, to date, evaluated the impact of alexithymia on these parameters. Therefore, the aim of the present cross-sectional study was to evaluate the relationship between alexithymia, suicide risk, C-reactive protein (CRP) and serum lipid levels in adult outpatients suffering from moderate to severe MD. CRP and serum lipid levels data were analyzed in 145 drug-naïve adult outpatients (69 men, 76 women) with a DSM-IV diagnosis of MD. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), depression severity was evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D) and suicide risk was determined using the Scale of Suicide Ideation (SSI). Alexithymics showed altered serum lipid levels and higher CRP than non-alexithymics. In the linear regression models, lower total cholesterol levels and "Difficulty in Identifying Feelings" dimension of TAS-20 were significantly associated with depression severity, whereas lower high-density lipoprotein levels and "Difficulty in Identifying and Describing Feelings" dimensions of TAS-20 were associated with higher suicide risk. Authors discuss study limitations and future research needs.
Event-related potential study of the effects of emotional facial expressions on task performance in euthymic bipolar patients.
Applied psychophysiology and biofeedback, 2011

There appears to be a significant disconnect between symptomatic and functional recovery in bipolar disorder (BD). Some evidence points to interepisode cognitive dysfunction. We tested the hypothesis that some of this dysfunction was related to emotional reactivity in euthymic bipolar subjects may effect cognitive processing. A modification of emotional gender categorization oddball task was used. The target was gender (probability 25%) of faces with negative, positive, and neutral emotional expression. The experiment had 720 trials (3 blocks × 240 trials each). Each stimulus was presented for 150 ms, and the EEG/ERP responses were recorded for 1,000 ms. The inter-trial interval was varied in 1,100-1,500 ms range to avoid expectancy effects. Task took about 35 min to complete. There were 9 BD and 9 control subjects matched for age and gender. Reaction time (RT) was globally slower in BD subjects. The centro-parietal amplitudes at N170 and N200, and P200 and P300 were generally smaller in the BD group compared to controls. Latency was shorter to neutral and negative targets in BD. Frontal P200 amplitude was higher to emotional negative facial non-targets in BD subjects. The frontal N200 in response to positive facial emotion was less negative in BD subjects. The frontal P300 of BD subjects was lower to emotionally neutral targets. ERP responses to facial emotion in BD subjects varied significantly from normal controls. These variations are consistent with the common depressive symptomology seen in long term studies of bipolar subjects.
Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease.
Chinese medical journal, 2017

Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD.
Intranasal oxytocin modulates neural functional connectivity during human social interaction.
American journal of primatology, 2018

Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals.
Loss of CLOCK Results in Dysfunction of Brain Circuits Underlying Focal Epilepsy.
Neuron, 2017

Because molecular mechanisms underlying refractory focal epilepsy are poorly defined, we performed transcriptome analysis on human epileptogenic tissue. Compared with controls, expression of Circadian Locomotor Output Cycles Kaput (CLOCK) is decreased in epileptogenic tissue. To define the function of CLOCK, we generated and tested the Emx-Cre; Clock
Subdural hematoma as a major determinant of short-term outcomes in traumatic brain injury.
Journal of neurosurgery, 2018

OBJECTIVE Early radiographic findings in patients with traumatic brain injury (TBI) have been studied in hopes of better predicting injury severity and outcome. However, prior attempts have generally not considered the various types of intracranial hemorrhage in isolation and have typically not excluded patients with potentially confounding extracranial injuries. Therefore, the authors examined the associations of various radiographic findings with short-term outcome to assess the potential utility of these findings in future prognostic models. METHODS The authors retrospectively identified 1716 patients who had experienced TBI without major extracranial injuries, and categorized them into the following TBI subtypes: subdural hematoma (SDH), traumatic subarachnoid hemorrhage, intraparenchymal hemorrhage (which included intraventricular hemorrhage), and epidural hematoma. They specifically considered isolated forms of hemorrhage, in which only 1 subtype was present. RESULTS In general, the presence of an isolated SDH was more likely to result in worse outcomes than the presence of other isolated forms of traumatic intracranial hemorrhage. Discharge to home was less likely and perihospital mortality rates were generally higher in patients with SDH. These findings were not simply related to age and were not fully captured by the admission Glasgow Coma Scale (GCS) score. The presence of SDH had a much higher sensitivity for poor outcome than the presence of other TBI subtypes, and was more sensitive for these poor outcomes than having a low GCS score (3-8). CONCLUSIONS In these ways, SDH was the most important finding associated with poor outcome, and the authors show that consideration of SDH, specifically, can augment age and GCS score in classification and prognostic models for TBI.
Soluble CD146 in cerebrospinal fluid of active multiple sclerosis.
Neuroscience, 2013

The soluble form of CD146 has been reported to be present in various inflammatory diseases and displays pro-inflammatory properties. However, little is known about sCD146 in multiple sclerosis (MS). Here we show that sCD146 is significantly elevated in the cerebrospinal fluid of patients with active MS compared with that of inactive MS or patients with non-demyelinating diseases. Moreover, abnormally increased sCD146 in the CSF of active MS patients correlated with albumin quotient, MBP antibody and MOG antibody from both CSF and sera. Importantly, the level of CSF sCD146 is correlated with levels of inflammatory factors, such as TNFα, IFNγ, IL-2, and IL-17A in the CSF. We also found that CSF sCD146 might originate from membrane-bound CD146 on inflamed blood-brain barrier (BBB) endothelial cells. In addition, sCD146 promotes leukocyte transmigration in vitro, at least in part by stimulating the expression of ICAM-1 and VCAM-1 on endothelial cells. Our findings suggest that CSF levels of sCD146 may provide a potential marker for monitoring disease activity in MS patients.
Heterogeneous presentation of caspr2 antibody-associated peripheral neuropathy - A case series.
European journal of pain (London, England), 2020

Contactin-associated protein 2-like (caspr2) antibodies have been discovered recently. Since then a multitude of patients with caspr2 antibodies presenting with different neurological symptoms have been reported. Here, we describe three patients with caspr2 antibodies with different types of pain/no pain in combination with peripheral neuropathy. The first patient, a 33-year-old woman, presented with erythromelalgia-like pain and autonomic symptoms; the second patient, a 58-year-old man, with paresthesia and pain while walking together with signs of peripheral motor neuron hyperexcitability in combination with optic neuritis, and the third patient, a 74-year-old man, without any pain but with polyneuropathy and encephalopathy. These cases illustrate the spectrum of symptoms in anti-caspr2 diseases. The pain in such cases can be treated causally.
Effects of ethanol exposure and withdrawal on dendritic morphology and spine density in the nucleus accumbens core and shell.
Brain research, 2015

Exposure to drugs of abuse can result in profound structural modifications on neurons in circuits involved in addiction that may contribute to drug dependence, withdrawal and related processes. Structural alterations on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) have been observed following exposure to and withdrawal from a variety of drugs; however, relatively little is known about the effects of alcohol exposure and withdrawal on structural alterations of NAc MSNs. In the present study male rats were chronically exposed to vaporized ethanol for 10 days and underwent 1 or 7 days of withdrawal after which the brains were processed for Golgi-Cox staining and analysis of dendritic length, branching and spine density. MSNs of the NAc shell and core underwent different patterns of changes following ethanol exposure and withdrawal. At 1 day of withdrawal there were modest reductions in the dendritic length and branching of MSNs in both the core and the shell compared to control animals exposed only to air. At 7 days of withdrawal the length and branching of shell MSNs was reduced, whereas the length and branching of core MSNs were increased relative to the shell. The density of mature spines was increased in the core at 1 day of withdrawal, whereas the density of less mature spines was increased in both regions at 7 days of withdrawal. Collectively, these observations indicate that MSNs of the NAc core and shell undergo distinct patterns of structural modifications following ethanol exposure and withdrawal suggesting that modifications in dendritic structure in these regions may contribute differentially to ethanol withdrawal.
Short-term Heat Exposure Promotes Hippocampal Neurogenesis via Activation of Angiotensin II Type 1 Receptor in Adult Rats.
Neuroscience, 2018

Angiotensin II (Ang II) synthesized in response to body fluid loss caused by actions such as sweating and breathing is today considered as one of the essential factors for promoting hippocampal neurogenesis. Because heat stimuli, along with exercise, increase systemic levels of Ang II, the effects of short-term heat exposure on hippocampal neurogenesis were examined in adult male rats. When rats were exposed daily to a 1-h heat treatment (36.0 ± 0.1 °C) during a 7-d experimental period, the number of doublecortin-immunoreactive newborn cells in the hippocampal dentate gyrus was increased approximately 1.4-fold compared with that in controls that were exposed to a normothermic environment (25.0 ± 0.8 °C). No significant change was observed in the number of Ki-67-immunoreactive stem cells. Western blot and immunohistochemical analyses revealed an enhancement of vascular endothelial growth factor (VEGF) expression in hippocampal astrocytes following short-term heat exposure. These beneficial effects of short-term heat exposure were prevented when an antagonist for Ang II type 1 receptor (AT1R), candesartan, was given orally. These results indicate that short-term heat exposure enhances adult neurogenesis via activation of AT1R in the hippocampal dentate gyrus, in which VEGF may participate by promoting cell proliferation and/or newborn neuron survival.
Threshold mechanism for saccade initiation in frontal eye field and superior colliculus.
Journal of neurophysiology, 2013

In an influential model of frontal eye field (FEF) and superior colliculus (SC) activity, saccade initiation occurs when the discharge rate of either single neurons or a population of neurons encoding a saccade motor plan reaches a threshold level of activity. Conflicting evidence exists for whether this threshold is fixed or can change under different conditions. We tested the fixed-threshold hypothesis at the single-neuron and population levels to help resolve the inconsistency between previous studies. Two rhesus monkeys performed a randomly interleaved pro- and antisaccade task in which they had to look either toward (pro) or 180° away (anti) from a peripheral visual stimulus. We isolated visuomotor (VM) and motor (M) neurons in the FEF and SC and tested three specific predictions of a fixed-threshold hypothesis. We found little support for fixed thresholds. First, correlations were never totally absent between presaccadic discharge rate and saccadic reaction time when examining a larger (plausible) temporal period. Second, presaccadic discharge rates varied markedly between saccade tasks. Third, visual responses exceeded presaccadic motor discharges for FEF and SC VM neurons. We calculated that only a remarkably strong bias for M neurons in downstream projections could render the fixed-threshold hypothesis plausible at the population level. Also, comparisons of gap vs. overlap conditions indicate that increased inhibitory tone may be associated with stability of thresholds. We propose that fixed thresholds are the exception rather than the rule in FEF and SC, and that stabilization of an otherwise variable threshold depends on task-related, inhibitory modulation.
Event conjunction: How the hippocampus integrates episodic memories across event boundaries.
Hippocampus, 2020

Our lives are a continuous stream of experience. Our episodic memories on the other hand have a definitive beginning, middle, and end. Theories of event segmentation suggest that salient changes in our environment produce event boundaries which partition the past from the present and, as a result, produce discretized memories. However, event boundaries cannot completely discretize two memories; any shared conceptual link will lead to the rapid integration of these memories. Here, we present a new framework inspired by electrophysiological research that resolves this apparent contradiction. At its heart, the framework proposes that hippocampal theta-gamma coupling maintains a highly abstract model of an ongoing event and serves to encode this model as an episodic memory. When a second but related event begins, this theta-gamma model is rapidly reconstructed within the hippocampus where new details of the second event can be appended to the existing event model. The event conjunction framework is the first electrophysiological explanation of how event memories can be formed at, and integrated across, event boundaries.
Leukoaraiosis and increased cerebral susceptibility to ischemia: lack of confounding by carotid disease.
Journal of the American Heart Association, 2013

Leukoaraiosis is associated with an increased risk of stroke, but the underlying mechanism remains uncertain, as do the associations with other risk factors, such as carotid disease. We aimed to determine the role of carotid disease and of other clinical variables in the development of leukoaraiosis and to define their contributions to the associated increased risk of stroke.
Intracerebral Hemorrhage Incidence, Mortality, and Association With Oral Anticoagulation Use: A Population Study.
Stroke, 2021

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke associated with significant morbidity and mortality. Recent epidemiological data on incidence, mortality, and association with oral anticoagulation are needed.
Cytokine mRNA induction by interleukin-1beta or tumor necrosis factor alpha in vitro and in vivo.
Brain research, 2008

Hypothalamic and cortical mRNA levels for cytokines such as interleukin-1beta (IL1beta), tumor necrosis factor alpha (TNFalpha), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) are impacted by systemic treatments of IL1beta and TNFalpha. To investigate the time course of the effects of IL1beta and TNFalpha on hypothalamic and cortical cytokine gene expression, we measured mRNA levels for IL1beta, TNFalpha, interleukin-6 (IL-6), interleukin-10 (IL-10), IL1 receptor 1, BDNF, NGF, and glutamate decarboxylase-67 in vitro using hypothalamic and cortical primary cultures. IL1beta and TNFalpha mRNA levels increased significantly in a dose-dependent fashion after exposure to either IL1beta or TNFalpha. IL1beta increased IL1beta mRNA in both the hypothalamic and cortical cultures after 2-6 h while TNFalpha mRNA increased significantly within 30 min and continued to rise up to 2-6 h. Most of the other mRNAs showed significant changes independent of dose in vitro. In vivo, intracerebroventricular (icv) injection of IL1beta or TNFalpha also significantly increased IL1beta, TNFalpha and IL6 mRNA levels in the hypothalamus and cortex. IL1beta icv, but not TNFalpha, increased NGF mRNA levels in both these areas. Results support the hypothesis that centrally active doses of IL1beta and TNFalpha enhance their own mRNA levels as well as affect mRNA levels for other neuronal growth factors.
High frequency rTMS over the left parietal lobule increases non-word reading accuracy.
Neuropsychologia, 2012

Increasing evidence in the literature supports the usefulness of Transcranial Magnetic Stimulation (TMS) in studying reading processes. Two brain regions are primarily involved in phonological decoding: the left superior temporal gyrus (STG), which is associated with the auditory representation of spoken words, and the left inferior parietal lobe (IPL), which operates in phonological computation. This study aimed to clarify the specific contribution of IPL and STG to reading aloud and to evaluate the possibility of modulating healthy participants' task performance using high frequency repetitive TMS (hf-rTMS). The main finding is that hf-rTMS over the left IPL improves non-word reading accuracy (fewer errors), whereas hf-rTMS over the right STG selectively decreases text-reading accuracy (more errors). These results confirm the prevalent role of the left IPL in grapheme-to-phoneme conversion. The non-word reading improvement after Left-IPL stimulation provide a direct link between left IPL activation and advantages in sublexical procedures, mainly involved in non-word reading. Results indicate also the specific involvement of STG in reading morphologically complex words and in processing the representation of the text. The text reading impairment after stimulation of the right STG can be interpreted in light of an inhibitory influence on the homologous area. In sum, data document that hf-rTMS is effective in modulating the reading accuracy of expert readers and that the modulation is task related and site specific. These findings suggest new perspectives for the treatment of reading disorders.
HPA axis regulation and epigenetic programming of immune-related genes in chronically stressed and non-stressed mid-life women.
Brain, behavior, and immunity, 2021

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation has been associated with altered immune function, but the underlying molecular mechanisms are unclear. Epigenetic processes, including DNA methylation, respond to the glucocorticoid end-products of the HPA axis (cortisol in humans) and could be involved in this neuroendocrine-immune crosstalk. Here we examined the extent to which variations in HPA axis regulation are associated with peripheral blood DNA (CpG) methylation changes in 57 chronically stressed caregivers and 67 control women. DNA methylation was determined with the Illumina 450k array for a panel of genes involved in HPA axis and immune function. HPA axis feedback was assessed with the low-dose dexamethasone suppression test (DST), measuring the extent to which cortisol secretion is suppressed by the synthetic glucocorticoid dexamethasone. After multiple testing correction in the entire cohort, higher post-DST cortisol, reflecting blunted HPA axis negative feedback, but not baseline waking cortisol, was associated with lower DNA methylation at eight TNF and two FKBP5 CpG sites. Caregiver group status was associated with lower methylation at two IL6 CpG sites. Since associations were most robust with TNF methylation (32% of the 450k-covered sites), we further examined functionality of this epigenetic signature in cultured peripheral blood mononuclear cells in 33 participants; intriguingly, lower TNF methylation resulted in higher ex vivo TNF mRNA following immune stimulation. Taken together, our findings link chronic stress and HPA axis regulation with epigenetic signatures at immune-related genes, thereby providing novel insights into how aberrant HPA axis function may contribute to heightened inflammation and disease risk.