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Laryngoscope Investigative... Oct 2023Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes,...
OBJECTIVE
Despite 6%-20% of the adult population suffering from tinnitus, there is no standard treatment for it. Placenta extract has been used for various therapeutic purposes, including hearing loss. Here, we evaluate the effect of a novel neuroprotective protein composition (NPPC) extract on electrophysiological and molecular changes in the medial geniculate body (MGB) of tinnitus-induced rats.
METHODS
To evaluate the protein analysis by western blot, the rats were divided into three groups: (1) saline group (intraperitoneal injection of 200 mg/kg saline twice a day for 28 consecutive days, (2) chronic Na-Sal group received sodium salicylate as in the first group, and (3) chronic treatment group (received salicylate 200 mg/kg twice daily for 2 weeks, followed by 0.4 mg NPPC daily from day 14 to day 28). Single-unit recordings were performed on a separate group that was treated as in group 4. Gap-prepulse inhibition of the acoustic startle (GPIAS) and pre-pulse inhibition (PPI) was performed to confirm tinnitus in all groups at the baseline, 14th and 28th days.
RESULTS
Western blot analysis showed that the expression of γ-Aminobutyric acid Aα1 subunit (GABA Aα1), N-methyl-d-aspartate receptor subtype 2B (NR2B or NMDAR2B), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR1 (GluR1), and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors subunit GluR2 (GluR2) decreased after Na-Sal injection, while NPPC upregulated their expression. MGB units in rats with tinnitus showed decreased spontaneous firing rate, burst per minute, and a spike in a burst. After NPPC administration, neural activity patterns showed a significant positive effect of NPPC on tinnitus.
CONCLUSION
NPPC can play an effective role in the treatment of tinnitus in salicylate-induced rats, and MGB is one of the brain areas involved in these processes.
LEVEL OF EVIDENCE
NA.
PubMed: 37899856
DOI: 10.1002/lio2.1156 -
Developmental Neuroscience Oct 2023The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies...
The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress. The use of variable frequency ultrasound in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of prenatal stress induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.
PubMed: 37857257
DOI: 10.1159/000534687 -
Translational Psychiatry Oct 2023Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic...
Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic startle response and prepulse inhibition (PPI) of startle are widely used translational measures for assessing sensory processing and sensorimotor gating, respectively. The Cntnap2 knockout (KO) rat has proven to be a valid model for ASD, displaying core symptoms, including sensory processing perturbations. Here, we used a novel method to assess startle and PPI in Cntnap2 KO rats that allows for the identification of separate scaling components: startle scaling, which is a change in startle amplitude to a given sound, and sound scaling, which reflects a change in sound processing. Cntnap2 KO rats show increased startle due to both an increased overall response (startle scaling) and a left shift of the sound/response curve (sound scaling). In the presence of a prepulse, wildtype rats show a reduction of startle due to both startle scaling and sound scaling, whereas Cntnap2 KO rats show normal startle scaling, but disrupted sound scaling, resulting in the reported PPI deficit. These results validate that startle and sound scaling by a prepulse are indeed two independent processes, with only the latter being impaired in Cntnap2 KO rats. As startle scaling is likely related to motor output and sound scaling to sound processing, this novel approach reveals additional information on the possible cause of PPI disruptions in preclinical models.
Topics: Animals; Rats; Acoustic Stimulation; Autism Spectrum Disorder; Prepulse Inhibition; Reflex, Startle; Sensory Gating
PubMed: 37852987
DOI: 10.1038/s41398-023-02629-6 -
Biological Psychology Nov 2023A weak stimulus presented immediately before a more intense one reduces both the N1-P2 cortical response and the perceived intensity of the intense stimulus. The former...
N1-P2 event-related potentials and perceived intensity are associated: The effects of a weak pre-stimulus and attentional load on processing of a subsequent intense stimulus.
A weak stimulus presented immediately before a more intense one reduces both the N1-P2 cortical response and the perceived intensity of the intense stimulus. The former effect is referred to as cortical prepulse inhibition (PPI), the latter as prepulse inhibition of perceived stimulus intensity (PPIPSI). Both phenomena are used to study sensory gating in clinical and non-clinical populations, however little is known about their relationship. Here, we investigated 1) the possibility that cortical PPI and PPIPSI are associated, and 2) how they are affected by attentional load. Participants were tasked with comparing the intensity of an electric pulse presented alone versus one preceded 200 ms by a weaker electric prepulse (Experiment 1), or an acoustic pulse presented alone with one preceded 170 ms by a weaker acoustic prepulse (Experiment 2). A counting task (easy vs. hard) manipulating attentional load was included in Experiment 2. In both experiments, we observed a relationship between N1-P2 amplitude and perceived intensity, where greater cortical PPI was associated with a higher probability of perceiving the 'pulse with prepulse' as less intense. Moreover, higher attentional load decreased observations of PPIPSI but had no effect on N1-P2 amplitude. Based on the findings we propose that PPIPSI partially relies on the allocation of attentional resources towards monitoring cortical channels that process stimulus intensity characteristics such as the N1-P2 complex.
Topics: Humans; Reflex, Startle; Acoustic Stimulation; Evoked Potentials; Prepulse Inhibition; Attention
PubMed: 37832864
DOI: 10.1016/j.biopsycho.2023.108711 -
Neurobiology of Learning and Memory Nov 2023Remembering an unfamiliar person and the contextual conditions of that encounter is important for adaptive future behavior, especially in a potentially dangerous...
Remembering an unfamiliar person and the contextual conditions of that encounter is important for adaptive future behavior, especially in a potentially dangerous situation. Initiating defensive behavior in the presence of former dangerous circumstances can be crucial. Recent studies showed selective electrocortical processing of faces that were previously seen in a threat context compared to a safety context, however, this was not reflected in conscious recognition performance. Here, we investigated whether previously seen threat-faces, that could not be remembered, were capable to activate defensive psychophysiological response systems. During an encoding phase, 50 participants with low to moderate levels of anxiety viewed 40 face pictures with neutral expressions (6 s each), without an explicit learning instruction (incidental learning task). Each half of the faces were presented with contextual background colors that signaled either threat-of-shock or safety. In the recognition phase, all old and additional new faces (total of 60) were presented intermixed without context information. Participants had to decide whether a face was new or had been presented previously in a threatening or a safe context. Results show moderate face recognition independent of context conditions. Startle reflex and skin conductance responses (SCR) were more pronounced for threat compared to safety during encoding. For SCR, this differentiation was enhanced with higher levels of depression and anxiety. There were no differential startle reflex or SCR effects during recognition. From a clinical perspective, these findings do not support the notion that perceptual biases and physiological arousal directly relate to threat-associated identity recognition deficits in healthy and clinical participants with anxiety and trauma-related disorders.
Topics: Humans; Fear; Anxiety; Learning; Mental Recall; Recognition, Psychology; Reflex, Startle
PubMed: 37832817
DOI: 10.1016/j.nlm.2023.107838 -
Ultrasonics Jan 2024Rodent models of behavior used in the fields of neuroscience and psychology generate a wealth of multimodal data. For instance, as a rodent moves and behaves in its...
Rodent models of behavior used in the fields of neuroscience and psychology generate a wealth of multimodal data. For instance, as a rodent moves and behaves in its environment, muscle contractions apply subtle forces to any surface the animal contacts. These forces generate acoustic waves that propagate through the waveguide as Lamb and shear horizontal (SH) waves and contain information about the rodent's physiology, behavior, and underlying psychological state. If the information in these waves were to be tapped, it would provide a novel, non-invasive way to study rodent behavior. This article lays the foundations for using guided ultrasonic waves generated by a mouse's movement on an aluminum plate for detecting behavior and drawing inferences about acoustic startle responses. The experimental setup involves piezoelectric sensors capturing the waves generated by the rodent's movement, which are then stored as discrete acoustic emission (AE) hits using an amplitude threshold-based data acquisition system. This method of data acquisition ensures that data collection occurs only when the animal moves or behaves, and each movement/behavior is represented by values of features within the generated wavepackets (AE hits). Through open field tests with C57BL/6J mice, utilizing piezoelectric sensors and the DAQ system, it was observed that every movement/behavior of the animal generated Lamb wavepackets within the frequency range of 20 kHz to 100 kHz. Furthermore, rearing behavior in the animals also led to the generation of SH wavepackets in the frequency range of 75 kHz to 230 kHz. This criterion was subsequently employed to detect rearing behavior. In the acoustic startle response test, where the animals' responses to intense sound pulse were recorded, AE hits' features proved useful in quantifying the response. These experimental findings validate the proposed technology's practicality and demonstrate its capability to enhance studies of rodent behavior.
Topics: Animals; Mice; Acoustics; Mice, Inbred C57BL; Reflex, Startle; Rodentia; Sound
PubMed: 37806079
DOI: 10.1016/j.ultras.2023.107170 -
International Journal of... Dec 2023Examining appetitive and aversive responses toward body image stimuli of those with disordered eating may illuminate motivational systems unique to eating pathology. The...
Facial EMG startle response and self-report reactions after exposure to severely underweight and severely obese body images in individuals with disordered eating: An examination of motivational responses.
Examining appetitive and aversive responses toward body image stimuli of those with disordered eating may illuminate motivational systems unique to eating pathology. The current study extended previous literature by examining self-report and startle responses to a range of body sizes. In this cross-sectional design, female, adult participants (n = 45) were sorted into disordered eating (DE; n = 22) and healthy control (HC; n = 23) groups based on Eating Disorder Examination Questionnaire global scores that were one standard deviation above or below normative values. Participants viewed eight computer-generated female body pictures from each group: severely underweight (BMI < 16.0), average (BMI 18.5-24.99), and severely obese (BMI > 40.0). Startle responses and self-reported valence and anxiety scores were collected to assess implicit and explicit reactions. 2 × 3 ANCOVA/ANOVAs were used to examine startle responses and self-report differences between groups, in response to image types. Results indicated startle responses did not differ between groups. There was a significant main effect for body picture type (p < .001), after controlling for psychotropic medication. Startle responses were higher for severely underweight body images compared to severely obese body images, although non-significant at post-hoc. The DE group reported higher levels of anxiety and sadness when viewing body images compared to the HC group. Average bodies were rated as less anxiety provoking and more positive than severely underweight and obese bodies. Group differences in anxiety and valence scores could be due to more maladaptive cognitions related to fear of weight gain among people with disordered eating.
Topics: Adult; Humans; Female; Body Image; Self Report; Reflex, Startle; Cross-Sectional Studies; Thinness; Feeding and Eating Disorders; Obesity
PubMed: 37802389
DOI: 10.1016/j.ijpsycho.2023.112249 -
Journal of Neurotrauma Feb 2024Blast exposure causes serious complications, the most common of which are ear-related symptoms such as hearing loss and tinnitus. The blast shock waves can cause...
Blast exposure causes serious complications, the most common of which are ear-related symptoms such as hearing loss and tinnitus. The blast shock waves can cause neurodegeneration of the auditory pathway in the brainstem, as well as the cochlea, which is the primary receptor for hearing, leading to blast-induced tinnitus. However, it is still unclear which lesion is more dominant in triggering tinnitus, the peripheral cochlea or the brainstem lesion owing to the complex pathophysiology and the difficulty in objectively measuring tinnitus. Recently, gap detection tests have been developed and are potentially well-suited for determining the presence of tinnitus. In this study, we investigated whether the peripheral cochlea or the central nervous system has a dominant effect on the generation of tinnitus using a blast-exposed mouse model with or without earplugs, which prevent cochlear damage from a blast transmitted via the external auditory canal. The results showed that the earplug (+) group, in which the cochlea was neither physiologically nor histologically damaged, showed a similar extent of tinnitus behavior in a gap prepulse inhibition of acoustic startle reflex test as the earplug (-) group, in which the explosion caused a cochlear synaptic loss in the inner hair cells and demyelination of auditory neurons. In contrast, both excitatory synapses labeled with VGLUT-1 and inhibitory synapses labeled with GAD65 were reduced in the ventral cochlear nucleus, and demyelination in the medial nucleus of the trapezoid body was observed in both groups. These disruptions significantly correlated with the presence of tinnitus behavior regardless of cochlear damage. These results indicate that the lesion in the brainstem could be dominant to the cochlear lesion in the development of tinnitus following blast exposure.
Topics: Mice; Animals; Tinnitus; Acoustic Stimulation; Explosions; Cochlea; Demyelinating Diseases
PubMed: 37795561
DOI: 10.1089/neu.2023.0259 -
Scientific Reports Oct 2023Acoustic Harassment Devices (AHD) are widely used to deter marine mammals from aquaculture depredation, and from pile driving operations that may otherwise cause hearing...
Acoustic Harassment Devices (AHD) are widely used to deter marine mammals from aquaculture depredation, and from pile driving operations that may otherwise cause hearing damage. However, little is known about the behavioural and physiological effects of these devices. Here, we investigate the physiological and behavioural responses of harbour porpoises (Phocoena phocoena) to a commercial AHD in Danish waters. Six porpoises were tagged with suction-cup-attached DTAGs recording sound, 3D-movement, and GPS (n = 3) or electrocardiogram (n = 2). They were then exposed to AHDs for 15 min, with initial received levels (RL) ranging from 98 to 132 dB re 1 µPa (rms-fast, 125 ms) and initial exposure ranges of 0.9-7 km. All animals reacted by displaying a mixture of acoustic startle responses, fleeing, altered echolocation behaviour, and by demonstrating unusual tachycardia while diving. Moreover, during the 15-min exposures, half of the animals received cumulative sound doses close to published thresholds for temporary auditory threshold shifts. We conclude that AHD exposure at many km can evoke both startle, flight and cardiac responses which may impact blood-gas management, breath-hold capability, energy balance, stress level and risk of by-catch. We posit that current AHDs are too powerful for mitigation use to prevent hearing damage of porpoises from offshore construction.
Topics: Animals; Porpoises; Phocoena; Noise; Reflex, Startle; Sound; Acoustics
PubMed: 37794093
DOI: 10.1038/s41598-023-43453-8 -
Molecular Psychiatry Sep 2023Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored...
Repeated low doses of psilocybin increase resilience to stress, lower compulsive actions, and strengthen cortical connections to the paraventricular thalamic nucleus in rats.
Psilocybin (a classic serotonergic psychedelic drug) has received appraisal for use in psychedelic-assisted therapy of several psychiatric disorders. A less explored topic concerns the use of repeated low doses of psychedelics, at a dose that is well below the psychedelic dose used in psychedelic-assisted therapy and often referred to as microdosing. Psilocybin microdose users frequently report increases in mental health, yet such reports are often highly biased and vulnerable to placebo effects. Here we establish and validate a psilocybin microdose-like regimen in rats with repeated low doses of psilocybin administration at a dose derived from occupancy at rat brain 5-HT receptors in vivo. The rats tolerated the repeated low doses of psilocybin well and did not manifest signs of anhedonia, anxiety, or altered locomotor activity. There were no deficits in pre-pulse inhibition of the startle reflex, nor did the treatment downregulate or desensitize the 5-HT receptors. However, the repeated low doses of psilocybin imparted resilience against the stress of multiple subcutaneous injections, and reduced the frequency of self-grooming, a proxy for human compulsive actions, while also increasing 5-HT receptor expression and synaptic density in the paraventricular nucleus of the thalamus. These results establish a well-validated regimen for further experiments probing the effects of repeated low doses of psilocybin. Results further substantiate anecdotal reports of the benefits of psilocybin microdosing as a therapeutic intervention, while pointing to a possible physiological mechanism.
Topics: Humans; Animals; Rats; Psilocybin; Hallucinogens; Midline Thalamic Nuclei; Resilience, Psychological; Serotonin; Compulsive Behavior
PubMed: 37783788
DOI: 10.1038/s41380-023-02280-z