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As disturbance in auditory steady-state response (ASSR) has been consistently found in many neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, there is considerable interest in the development of translational rat models to elucidate the underlying neural and neurochemical mechanisms involved in ASSR. This is the first study to investigate the effects of the non-selective muscarinic antagonist scopolamine and the cholinesterase inhibitor donepezil (also in combination with scopolamine) on ASSR. We recorded the local field potentials through the chronic microelectrodes implanted in the auditory cortex of freely moving rat. ASSRs were recorded in response to auditory stimuli delivered over a range of frequencies (10-80 Hz) and averaged over 60 trials. We found that a single dose of scopolamine produced a temporal attenuation in response to auditory stimuli; the most attenuation occurred at 40 Hz. Time-frequency analysis revealed deficits in both power and phase-locking to 40 Hz. Donepezil augmented 40-Hz steady-state power and phase-locking. Scopolamine combined with donepezil had an enhanced effect on the phase-locking, but not power of ASSR. These changes induced by cholinergic drugs suggest an involvement of muscarinic neurotransmission in auditory processing and provide a rodent model investigating the neurochemical mechanism of neurophysiological deficits seen in patients.

A new mecarbinate derivative, ethyl 6-bromo-5-((5-bromopyrimidin-2-yl)oxy)-2-((2,6- dimethylmorpholino)methyl)-1-methyl-1H-indole-3-carboxylate (1), was synthesized, and single crystals were grown by the gradual evaporation of acetone under ambient conditions. The optimized molecular crystal structure was determined based on DFT calculations at the B3LYP/6311G (2 d, p) level. Experimental and theoretical studies on the structure of the titled compound are presented.

Stress is known to elicit various adaptive or maladaptive responses in the nervous system function. Psychophysical studies have revealed that stress exposure induced the changes in auditory response that can be interpreted as a transient, stress-induced hypersensitivity to sounds. However, the underlying neural mechanism remains unresolved. Thus, in this study, we explored the neural activities of the auditory cortex (AC) in response to stress. We elicited stress by physically immobilizing rats and recorded the extracellular single-unit activities through the electrodes chronically implanted in the AC of rats. By comparing the spike activities of the same rat before, during and after immobilization, we found temporal and significant changes in the sound-evoked neural activities. In most cases, acute restraint stress enhanced neural responses evoked by pure-tones and click-trains, but in a minority of neurons, stress suppressed responses. The immobilization-induced enhancement was more frequently found in the neurons that originally had a low responsibility for sound stimuli. The enhancement effects on pure-tone response were reflected by an increase of response magnitude, decrease of response latency, and extension of bandwidth of tuning curve (BW). But the spontaneous firing rate and best frequency (BF) remained unchanged. Stress also increased the ability of neural response to synchronize to click-trains, even in the neurons whose response magnitude was not significantly increased. Taken together, these results provide direct evidence that stress alters the function of auditory system at the level of AC.

Previous studies have suggested that elevation of glucocorticoid level can alter auditory processing and may have relevance for auditory hallucinations. However, the neural mechanism underlying the glucocorticoid induced sensory change remains unclear. To examine the effects of glucocorticoid on the neuronal spike activities of sensory cortex, we topically applied dexamethasone (DEX), a glucocorticoid receptor agonist, to the auditory cortical surface of rats while recording single-unit extracellular spike activities in response to sound stimuli. Our major findings are: (1) a topical administration of DEX increased the cortical neural responses to pure-tone stimuli from 10 to 60 min after administration, while the peak response enhancement occurred at 20-30 min; (2) DEX not only markedly increased the magnitude of tone-evoked responses, but also extended the response duration and the frequency range of the neural responses; (3) the enhancement of neural responses was more salient at the higher frequency band; (4) the ratio of spontaneous firing rate between post- and pre-administration was negatively correlated with the unit's spontaneous firing rate before treatment. Our data confirm that DEX can modulate the neural activity at the cortical level and provide more information for understanding the mechanism of glucocorticoid-induced alterations in auditory processing.

Deleted in pancreatic carcinoma locus 4 influences tumorigenesis and tumor progression by various mechanisms, including apoptosis. The aim of this study is to determine whether deleted in pancreatic carcinoma locus 4 participates in apoptosis in lung cancer and clarify its relationship with clinical parameters of non-small cell lung cancer. Immunohistochemical results revealed that the positive rate of deleted in pancreatic carcinoma locus 4 in normal tracheal-bronchial epithelium (89.5%, 17/19) was much higher than that in tumor tissues (63.5%, 33/52) (P < .05) and closely correlated with lymph node metastasis (P < .001). These results were further confirmed by Western blot analysis. Furthermore, deleted in pancreatic carcinoma locus 4 overexpression was inversely associated with Bcl-2 immunostaining (P < .01), and the apoptosis index in deleted in pancreatic carcinoma locus 4-positive carcinomas (8.65 +/- 1.46) was much higher than that in deleted in pancreatic carcinoma locus 4-negative carcinomas (2.12 +/- 0.04) (P < .05). The results of deleted in pancreatic carcinoma locus 4 small interfering RNA in A549 cells also showed that deleted in pancreatic carcinoma locus 4 could inhibit cell proliferation, decrease Bcl-2 mRNA and protein expression, and increase Bax messenger RNA and protein expression. These findings indicated that Deleted in pancreatic carcinoma locus 4 might be an important biomarker for malignant transformation and be involved in inducing apoptosis by modulating Bcl-2/Bax balance.