Animals ; Reflex, Startle ; Models, Animal ; Acoustics

Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.
Acoustics ; Animals ; Auditory Cortex ; Brain Stem ; Evoked Potentials, Auditory, Brain Stem ; Genes, Immediate-Early ; Glutamic Acid ; Immunohistochemistry ; Integrin alpha2 ; Memantine ; Models, Animal ; N-Methylaspartate ; Neurons ; Noise ; Prepulse Inhibition ; Rats ; Reflex, Startle ; Tinnitus ; Tumor Necrosis Factor-alpha

Gap prepulse inhibition of acoustic startle (GPIAS) method has been used effectively for the objective assessment of tinnitus in animals. Among two types of enclosures for the GPIAS, the unconstrained type carries less risk of animal death due to the absence of binding stress in the enclosure, and lack of need for alteration to animal size variation as it grows. However, animals' voluntary movements, which have no relation to the startles evoked by acoustic stimuli, are problematic, as they cannot be excluded in the case of the unconstrained enclosure based GPIAS measurement system. In order to discount voluntary movements which are not associated with external acoustic stimuli, we propose the conditional random interstimulus interval (CR ISI) method for unconstrained enclosure based GPIAS measurement. With the proposed ISI method, the unconstrained enclosure based acoustic startle response measurement system has been implemented in this paper. As a result, the effectiveness of the proposed CR ISI method has been verified and compared with those of conventional ISI methods through animal experiments using SD-rats. The experimental results showed that abnormal startle responses and invalid GPIAS values caused by motion were prevented when our proposed CR ISI method was applied to our implemented system. It was also verified that our proposed CR ISI method is advantageous in reducing the total experimental time for acquiring normal startle responses and valid GPIAS values, compared to conventional ISI methods, since our proposed CR ISI can begin the acoustic stimulation only when the animal gets stable and motionless.
Acoustic Stimulation ; Acoustics ; Animal Experimentation ; Animals ; Integrin alpha2 ; Methods ; Prepulse Inhibition ; Reflex, Startle ; Tinnitus

OBJECTIVE: Central 5-HT1A receptor is involved in the modulation of sensorimotor gating function. However, its precise role is not clearly defined in developmentally social deprived (isolation rearing, IR) rats featured with impaired sensorimotor gating ability. We therefore aimed to examine the effects of 5HT1A activation on acoustic startle response (ASR) and prepulse inhibition (PPI) in IR rats in a condition of compromised presynaptic 5-HT functions. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletor, 5,7-DHT. Seven days later rats entered a protocol of 8-OH-DPAT, a 5-HT1A agonist, in which locomotor activity, ASR and PPI and their tissue levels of 5-HT were measured. RESULTS: Our results found that both IR and 5,7-DHT decreased the tissue concentration of 5-HT. IR-induced hyperactivity and gating impairment were unaffected by 5-HT depletion. 8-OH-DPAT strengthened the ASR in IR but not SOC rats and the drug-reduced PPI could be adjusted by 5,7-DHT pretreatment. 8-OH-DPAT at 100 μg/kg enhanced PPI in 5-HT-depleted SOC rats. However for IR rats, 8-OH-DPAT strengthened PPI in sham rats but downgraded it in depletion condition. CONCLUSION: The integrity of central 5-HT system is important to 5-HT1A-modulated sensorimotor gating in isolation-reared rats.
8-Hydroxy-2-(di-n-propylamino)tetralin ; Acoustics ; Animals ; Motor Activity ; Prepulse Inhibition ; Rats ; Receptor, Serotonin, 5-HT1A ; Reflex, Startle ; Sensory Gating ; Serotonin ; Serotonin 5-HT1 Receptor Agonists ; Social Control, Formal

Familial hyperekplexia, also called startle disease, is a rare neurological disorder characterized by excessive startle responses to noise or touch. It can be associated with serious injury from frequent falls, apnea spells, and aspiration pneumonia. Familial hyperekplexia has a heterogeneous genetic background with several identified causative genes; it demonstrates both dominant and recessive inheritance in the α1 subunit of the glycine receptor (GLRA1), the β subunit of the glycine receptor and the presynaptic sodium and chloride-dependent glycine transporter 2 genes. Clonazepam is an effective medical treatment for hyperekplexia. Here, we report genetically confirmed familial hyperekplexia patients presenting early adult cautious gait. Additionally, we review clinical features, mode of inheritance, ethnicity and the types and locations of mutations of previously reported hyperekplexia cases with a GLRA1 gene mutation.
Accidental Falls ; Adult ; Apnea ; Clonazepam ; Gait* ; Genetic Background ; Glycine Plasma Membrane Transport Proteins ; Humans ; Nervous System Diseases ; Noise ; Phenotype* ; Pneumonia, Aspiration ; Receptors, Glycine ; Reflex, Startle ; Sodium ; Stiff-Person Syndrome* ; Wills

Infants with Sandhoff disease typically appear normal until 3–6 months of age. As the disease progresses, they present with symptoms such as loss of motor skills, exaggerated startle response to loud noise, seizures, visual loss, and paralysis. We encountered a rare case of a 22-month-old girl with Sandhoff disease characterized by progressive motor weakness and dysphagia, who initially showed signs of aspiration at 20 months of age. The major problems related to dysphagia were oromotor dysfunction and abnormal feeding posture. Within 3 months of identification of difficulty in swallowing, the patient showed a significant decrease in food intake, with rapid deterioration of nutritional status. We report our case with a review of the literature.
Deglutition Disorders ; Deglutition* ; Eating ; Female ; Humans ; Infant ; Motor Skills ; Noise ; Nutritional Status ; Paralysis ; Posture ; Reflex, Startle ; Sandhoff Disease* ; Seizures

BACKGROUNDNicotine may improve schizophrenia patient's cognitive deficit symptoms. This study was to explore the chronic effects of smoking on prepulse inhibition of the startle reflex (PPI) and P50 in the patients with first-episode schizophrenia (FES).

METHODSThe event-related potentials (ERP) recording and analysis instrument made by Brain Products, Germany, was used to detect PPI and P50 in 49 male FES patients (FES group, n = 21 for smokers and n = 28 for non-smokers) and 43 normal male controls (control group, n = 19 for smokers and n = 24 for non-smokers).

RESULTSCompared with normal controls, the FES group had prolonged PPI latency when elicited by single stronger stimulus (P < 0.05); the FES group had prolonged PPI latency and increased PPI amplitude (P < 0.05, 0.01) when elicited by weak and strong stimuli. The FES group had lower PPI inhibition rate than normal controls (P < 0.05). Compared with normal controls, the FES group had increased P50-S2 amplitude and increased amplitude ratio S2/S1 (both P <0.05). In the control group, the smokers had a tendency of increase in P50-S2 amplitude (P > 0.05) and shorter P50-S2 latency (P < 0.05) than the non-smokers. The smokers had higher PPI amplitude than the non-smokers (P < 0.05). In the FES group, the smokers had higher P50-S1 amplitude, shorter P50-S2 latency, and higher amplitude ratio S2/S1 than the non-smokers (P < 0.05, 0.01). The smokers had higher PPI amplitude than the non-smokers (P < 0.05).

CONCLUSIONSThere is obvious PPI and P50 deficits in schizophrenic patients. However, these deficits are relatively preserved in the smokers compared with the non-smokers, which suggests that long-term smoking might partially improve the sensory gating in schizophrenic patients. Whether this conclusion can be deduced to female patients requires further follow-ups.

Adult ; Case-Control Studies ; Evoked Potentials ; drug effects ; physiology ; Humans ; Male ; Reflex, Startle ; physiology ; Schizophrenia ; physiopathology ; Smoking ; adverse effects ; Young Adult

Prepulse inhibition (PPI) is suppression of the startle reflex when an intense startling stimulus is preceded by a weaker sensory stimulus (the prepulse). It is an operational measurement of sensorimotor gating mechanism to help human adapt to complex environment. This weak prepulse protect central cognitive processing by damping the effect of intense stimuli. Autistics cannot select out behaviorally important information from a lot of irrelevant resources and reflect abnormal gating mechanism and attentional abnormalities. Previous studies have not made agreement on whether autistic patients demonstrated deficits in PPI, because the results depend on age, sex, severity of the disease as well as the experimental parameters used. Moreover, these studies have not covered whether autistics have suffered deficits in higher-order processing. In this review, the "top-down" modulation of selective attention and subjective emotion are introduced into the PPI experiment. We also introduce fear conditioning and perceived spatial separation paradigm to further explore the interaction between autistic cognitive process and gating mechanism.
Attention ; Autistic Disorder ; Fear ; Humans ; Prepulse Inhibition ; Reflex, Startle

Prepulse inhibition (PPI) is considered to be one of the most promising neurophysiological indexes for translational research in psychiatry. Impairment of PPI has been reported in several psychiatric diseases, particularly schizophrenia, where PPI is considered a candidate intermediate phenotype (endophenotype) of the disease. Recent findings from a variety of research areas have provided important evidence regarding PPI impairment. Human brain imaging studies have demonstrated the involvement of the striatum, hippocampus, thalamus and frontal and parietal cortical regions in PPI. In addition, several genetic polymorphisms, including variations in the genes coding for Catechol O-methyltransferase, Neuregulin 1, nuclear factor kappa-B subunit 3 and serotonin-2A receptor were related to PPI; and these findings support PPI as a polygenetic trait that involves several neurotransmitter pathways. Early psychosis studies suggest that PPI disruption is present before the onset of psychosis. Also, discrepancy of PPI impairment between children and adults can be found in other psychiatric diseases, such as autistic spectrum disorders and posttraumatic stress disorder, and comprehensive investigation of startle response might contribute to understand the impairment of the neural circuitry in psychiatric diseases. Finally, recent studies with both Asian and Caucasian subjects indicate that patients with schizophrenia exhibit impaired PPI, and impaired sensorimotor gating might be a global common psychophysiological feature of schizophrenia. In conclusion, studies of PPI have successfully contributed to a better understanding of the fundamental neural mechanisms underlying sensorimotor gating and will certainly be most valuable in devising future approaches that aim to investigate the complex pathogenesis of psychiatric diseases.
Adult ; Asian Continental Ancestry Group ; Catechol O-Methyltransferase ; Catechols ; Child ; Clinical Coding ; Endophenotypes ; Hippocampus ; Humans ; Mental Disorders ; Neuregulin-1 ; Neuroimaging ; Neurotransmitter Agents ; Phenotype ; Polymorphism, Genetic ; Psychophysiology ; Psychotic Disorders ; Schizophrenia ; Sensory Gating ; Startle Reaction ; Stress Disorders, Post-Traumatic ; Thalamus ; Translational Medical Research

Brain Stem ; physiology ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases ; etiology ; Movement Disorders ; etiology ; Myoclonus ; etiology ; Reflex, Abnormal ; Reflex, Startle ; Tremor ; etiology