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Frontiers in Endocrinology 2024Polycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still...
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a common multifactorial and polygenic disorder of the endocrine system, affecting up to 20% of women in reproductive age with a still unknown etiology. Follicular fluid (FF) represents an environment for the normal development of follicles rich in metabolites, hormones and neurotransmitters, but in some instances of PCOS the composition can be different. Vasoactive intestinal peptide (VIP) is an endogenous autonomic neuropeptide involved in follicular atresia, granulosa cell physiology and steroidogenesis.
METHODS
ELISA assays were performed to measure VIP and estradiol levels in human follicular fluids, while AMH, FSH, LH, estradiol and progesterone in the plasma were quantified by chemiluminescence. UHPLC/QTOF was used to perform the untargeted metabolomic analysis.
RESULTS
Our ELISA and metabolomic results show: i) an increased concentration of VIP in follicular fluid of PCOS patients (n=9) of about 30% with respect to control group (n=10) (132 ± 28 pg/ml versus 103 ± 26 pg/ml, p=0,03) in women undergoing fertilization (IVF), ii) a linear positive correlation (p=0.05, r=0.45) between VIP concentration and serum Anti-Müllerian Hormone (AMH) concentration and iii) a linear negative correlation between VIP and noradrenaline metabolism. No correlation between VIP and estradiol (E2) concentration in follicular fluid was found. A negative correlation was found between VIP and noradrenaline metabolite 3,4-dihydroxyphenylglycolaldehyde (DOPGAL) in follicular fluids.
CONCLUSION
VIP concentration in follicular fluids was increased in PCOS patients and a correlation was found with noradrenaline metabolism indicating a possible dysregulation of the sympathetic reflex in the ovarian follicles. The functional role of VIP as noradrenergic modulator in ovarian physiology and PCOS pathophysiology was discussed.
Topics: Humans; Female; Polycystic Ovary Syndrome; Vasoactive Intestinal Peptide; Fertilization in Vitro; Follicular Fluid; Adult; Estradiol; Anti-Mullerian Hormone; Case-Control Studies
PubMed: 38774232
DOI: 10.3389/fendo.2024.1331282 -
The Journal of the Acoustical Society... May 2024Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise....
Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.
Topics: Animals; Female; Male; Mice; Acoustic Stimulation; Auditory Pathways; Auditory Perception; Auditory Threshold; Behavior, Animal; Cochlea; Evoked Potentials, Auditory, Brain Stem; Hearing; Mice, Inbred C57BL; Mice, Knockout; Noise; Olivary Nucleus; Perceptual Masking; Phenotype; Receptors, Nicotinic; Reflex, Startle
PubMed: 38738939
DOI: 10.1121/10.0025985 -
Behaviour Research and Therapy Jul 2024Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions,... (Randomized Controlled Trial)
Randomized Controlled Trial
Previous studies showed that glucose has beneficial effects on memory function and can enhance contextual fear learning. To derive potential therapeutic interventions, further research is needed regarding the effects of glucose on fear extinction. In two experimental studies with healthy participants (Study 1: N = 68, 39 females; Study 2: N = 89, 67 females), we investigated the effects of glucose on fear extinction learning and its consolidation. Participants completed a differential fear conditioning paradigm consisting of acquisition, extinction, and return of fear tests: reinstatement, and extinction recall. US-expectancy ratings, skin conductance response (SCR), and fear potentiated startle (FPS) were collected. Participants were pseudorandomized and double-blinded to one of two groups: They received either a drink containing glucose or saccharine 20 min before (Study 1) or immediately after extinction (Study 2). The glucose group showed a significantly stronger decrease in differential FPS during extinction (Study 1) and extinction recall (Study 2). Additionally, the glucose group showed a significantly lower contextual anxiety at test of reinstatement (Study 2). Our findings provide first evidence that glucose supports the process of fear extinction, and in particular the consolidation of fear extinction memory, and thus has potential as a beneficial adjuvant to extinction-based treatments. Registered through the German Clinical Trials Registry (https://www.bfarm.de/EN/BfArM/Tasks/German-Clinical-Trials-Register/_node.html; Study 1: DRKS00010550; Study 2: DRKS00018933).
Topics: Humans; Extinction, Psychological; Fear; Female; Male; Glucose; Adult; Young Adult; Double-Blind Method; Conditioning, Classical; Galvanic Skin Response; Reflex, Startle; Adolescent; Mental Recall
PubMed: 38728832
DOI: 10.1016/j.brat.2024.104553 -
Behaviour Research and Therapy Jul 2024Although observational fear learning has been implicated in the development of phobic-related fears, studies investigating observational learning of fear of bodily...
Although observational fear learning has been implicated in the development of phobic-related fears, studies investigating observational learning of fear of bodily symptoms remain scarce. Therefore, the aim of the present study was to investigate whether fear in response to bodily symptoms can be acquired simply by observing a fearful reaction to provocation of aversive bodily symptoms in others. Forty healthy participants underwent an observational fear conditioning paradigm consisting of two phases. In the first phase, participants observed a demonstrator reacting to an aversive bodily symptom provocation (unconditioned stimulus or US, i.e., labored breathing) paired with one conditioned stimulus (CS+) but not with the other one (CS-, both CSs were geometric symbols presented on a screen the demonstrator was watching). In the second phase, participants were directly presented with the same conditioned stimuli, but in the absence of the US. Our results revealed enhanced conditioned fear responses in the beginning of the second phase to the CS + as compared to CS-, as indexed by greater skin conductance and subjective fear responses, as well as greater potentiation of startle eyeblink responses to the CS + as compared to the ITI. Taken together, these findings implicate that fear of bodily symptoms can be learned through observation of others, that is, without first-hand experience of bodily threat.
Topics: Humans; Fear; Female; Male; Conditioning, Classical; Reflex, Startle; Young Adult; Galvanic Skin Response; Adult; Adolescent; Blinking
PubMed: 38718630
DOI: 10.1016/j.brat.2024.104555 -
Brain and Behavior May 2024Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to...
INTRODUCTION
Chronic adolescent stress profoundly affects prefrontal cortical networks regulating top-down behavior control. However, the neurobiological pathways contributing to stress-induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha-converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses.
METHODS
We used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re-experiencing of trauma.
RESULTS
Chronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle).
CONCLUSION
This study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.
Topics: Animals; Male; Rats; ADAM17 Protein; Behavior, Animal; Prefrontal Cortex; Rats, Inbred Lew; Reflex, Startle; Stress, Psychological; Female
PubMed: 38715397
DOI: 10.1002/brb3.3482 -
Epileptic Disorders : International... May 2024Herein, we present the case of a 21-year-old man with a history of generalized tonic seizures since the age of 4 years. These seizures occurred either spontaneously or...
Herein, we present the case of a 21-year-old man with a history of generalized tonic seizures since the age of 4 years. These seizures occurred either spontaneously or could be provoked by auditory stimuli such as the sounds of a vacuum cleaner or an electric shaver. Despite trials with 10 different anti-seizure medications, his seizures remained refractory. Interictal electroencephalography (EEG) revealed generalized epileptiform activity, whereas ictal EEG showed a generalized attenuation pattern. Magnetic resonance imaging revealed extensive chronic infarctions, predominantly in the bilateral cerebral watershed areas. At the age of 17, the patient underwent a one-stage complete callosotomy, which only achieved remission of auditory-provoked seizures. Based on this experience and published reports, we propose that the posterior corpus callosum, particularly the isthmus and anterior splenium, may be involved in seizures caused by unexpected sound stimuli.
PubMed: 38713433
DOI: 10.1002/epd2.20238 -
Schizophrenia Research Jul 202422q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS...
BACKGROUND
22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk.
METHODS
Startle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers.
RESULTS
Across the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed.
CONCLUSIONS
Reduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.
Topics: Humans; Male; Female; Reflex, Startle; Adult; Adolescent; Young Adult; DiGeorge Syndrome; Prepulse Inhibition; Blinking; Reaction Time; Electromyography; Acoustic Stimulation
PubMed: 38703519
DOI: 10.1016/j.schres.2024.04.022 -
Psychophysiology May 2024Prepulse inhibition (PPI) of the startle reflex serves as a pre-cognitive marker of sensorimotor gating, and its deficit may predict cognitive impairments. Startle...
Prepulse inhibition (PPI) of the startle reflex serves as a pre-cognitive marker of sensorimotor gating, and its deficit may predict cognitive impairments. Startle reflex is modulated by many factors. Among them, stress has been a topic of interest, but its effects on both pre-cognitive and cognitive variables continue to yield divergent results. This study aims to analyze the effect of acute stress on PPI of the startle reflex and cognitive function (working memory, attention, inhibition, and verbal fluency). Participants were exposed to the MAST stress induction protocol or a stress-neutral task: stress group (n = 54) or control group (n = 54). Following stress induction, participants' startle responses were recorded, and cognition was assessed. The results revealed that participants in the stress group exhibited greater startle magnitude, lower PPI, and lower scores in working memory tests compared with the control group. Additionally, a correlation was found between working memory and PPI across all the participants, independent of stress group. These findings support the notion that after stress, both greater startle magnitude and diminished PPI could play an adaptive role by allowing for increased processing of stimuli potentially dangerous and stress-related. Similarly, our results lend support to the hypothesis that lower PPI may be predictive of cognitive impairment. Considering the impact of stress on both pre-cognitive (PPI) and cognitive (working memory) variables, we discuss the possibility that the effect of stress on PPI occurs through motivational priming and emphasize the relevance of considering stress in both basic and translational science.
PubMed: 38691020
DOI: 10.1111/psyp.14599 -
Autonomic Neuroscience : Basic &... Jun 2024Unilateral nociceptive stimulation is associated with subtle signs of pupil asymmetry that may reflect lateralized activity in the locus coeruleus. To explore drivers of...
Unilateral nociceptive stimulation is associated with subtle signs of pupil asymmetry that may reflect lateralized activity in the locus coeruleus. To explore drivers of this pupil asymmetry, electrical stimuli, delivered alone or 200 ms before or after an acoustic startle stimulus, were administered to one ankle under four experimental conditions: with or without a 1.6 s anticipatory period, or while the forearm ipsilateral or contralateral to the electrical stimulus was heated tonically to induce moderate pain (15 healthy participants in each condition). Pupil diameter was measured at the start of each trial, at stimulus delivery, and each second for 5 s after stimulus delivery. At the start of the first trial, the pupil ipsilateral to the side on which electric shocks were later delivered was larger than the contralateral pupil. Both pupils dilated robustly during the anticipatory period and dilated further during single- and dual-stimulus trials. However, pupil asymmetry persisted throughout the experiment. Tonically-applied forearm heat-pain modulated the pupillary response to phasic electrical stimuli, with a slight trend for dilatation to be greater contralateral to the forearm being heated. Together, these findings suggest that focusing anxiously on the expected site of noxious stimulation was associated with dilatation of the ipsilateral pupil whereas phasic nociceptive stimuli and psychological arousal triggered bilateral pupillary dilatation. It was concluded that preparatory cognitive activity rather than phasic afferent nociceptive input is associated with pupillary signs of lateralized activity in the locus coeruleus.
Topics: Humans; Male; Pupil; Female; Young Adult; Adult; Electric Stimulation; Nociception; Reflex, Startle; Anticipation, Psychological; Functional Laterality; Pain; Hot Temperature
PubMed: 38677128
DOI: 10.1016/j.autneu.2024.103179 -
Brain Research Aug 2024Prepulse inhibition (PPI) of the auditory startle response, a key measure of sensorimotor gating, diminishes with age and is impaired in various neurological conditions....
Prepulse inhibition (PPI) of the auditory startle response, a key measure of sensorimotor gating, diminishes with age and is impaired in various neurological conditions. While PPI deficits are often associated with cognitive impairments, their reversal is routinely used in experimental systems for antipsychotic drug screening. Yet, the cellular and circuit-level mechanisms of PPI remain unclear, even under non-pathological conditions. We recently showed that brainstem neurons located in the caudal pontine reticular nucleus (PnC) expressing the glycine transporter type 2 (GlyT2) receive inputs from the central nucleus of the amygdala (CeA) and contribute to PPI but via an uncharted pathway. Here, using tract-tracing, immunohistochemistry and in vitro optogenetic manipulations coupled to field electrophysiological recordings, we reveal the neuroanatomical distribution of GlyT2 PnC neurons and PnC-projecting CeA glutamatergic neurons and we provide mechanistic insights on how these glutamatergic inputs suppress auditory neurotransmission in PnC sections. Additionally, in vivo experiments using GlyT2-Cre mice confirm that optogenetic activation of GlyT2 PnC neurons enhances PPI and is sufficient to induce PPI in young mice, emphasizing their role. However, in older mice, PPI decline is not further influenced by inhibiting GlyT2 neurons. This study highlights the importance of GlyT2 PnC neurons in PPI and underscores their diminished activity in age-related PPI decline.
Topics: Animals; Prepulse Inhibition; Neurons; Reflex, Startle; Mice; Brain Stem; Glycine Plasma Membrane Transport Proteins; Male; Glycine; Optogenetics; Mice, Transgenic; Mice, Inbred C57BL; Synaptic Transmission; Central Amygdaloid Nucleus
PubMed: 38615924
DOI: 10.1016/j.brainres.2024.148938