Gamma oscillations (30-80 Hz) have been demonstrated to be important for perceptual and cognitive processes. Animal and in vitro studies have revealed possible underlying generation mechanisms of the gamma rhythm. However, little is known about the neurochemical modulation of these oscillations during human cognition. Schizophrenia and Attention Deficit Hyperactivity Disorder, which lead to failure of attentional modulation and working memory, introduce significant changes in gamma responses and have significant associations with genetic polymorphisms of dopamine receptor D4 (DRD4), dopamine transporter (DAT), and catechol-O-methyltransferase (COMT). Therefore, the presence of direct relations between these polymorphisms and gamma oscillations was investigated in human subjects using an auditory target detection paradigm. The 7-repeat isoform of the DRD4 polymorphism that produces a subsensitive variant of the D4 receptor enhanced the auditory evoked and induced gamma responses to both standard and target stimuli. The 10/10 genotype of the DAT1 polymorphism, which reduces DAT expression and hence yields an increase in extracellular dopamine, specifically enhanced evoked gamma responses to target stimuli. The COMT polymorphism did not significantly change gamma responses. It seems plausible to assume that the modulation pattern of the evoked gamma response by DRD4 polymorphism relates to reduced inhibition via the D4 receptor, whereas the DAT1 effect is related to the target detection mechanism probably mediated by the D1 receptor.
Effects of mutations in the beta 2-adrenergic receptor (beta 2AR) gene on intraocular pressure (IOP), in response to acute dynamic exercise, were investigated in 19 healthy males (age 22.6 +/- 2.8 years). Intraocular pressures were measured pre- and post-exercise. Weight, height, body mass index, and maximal oxygen (VO2max) uptake were recorded and subjects were genotyped for Arg16Gly, Gln27Glu and Thr164Ile mutations of the beta 2AR gene. Post-exercise, reductions in mean IOP values were found in 16 subjects with the Gly16Gly and Arg16Gly genotypes, but these values remained low in the eight patients with the Gly16Gly genotype 3 h post-exercise, whereas they returned to baseline within 1 h in the eight subjects with the Arg16Gly genotype. beta 2AR stimulation during exercise could be an important regulator of IOP response and determining beta 2AR polymorphisms may improve understanding of pathogenesis and treatment selection in ophthalmic diseases, e.g. glaucoma.
Obstructive Sleep Apnea Syndrome (OSAS) is characterized by desaturation in blood oxygen level and sleep fragmentation because of repeated upper airway obstruction. Auditory Event related potentials (AERPs) are scalp recorded voltage fluctuations, which reflect several cognitive processes generated within specific brain regions during auditory stimulus processing. In this study, we aimed to investigate cognitive deficits in OSAS patients with AERPs by taking the effects of aging factor into consideration. AERPs were recorded using an auditory oddball paradigm from 27 OSAS patients (range 28 to 67 years old) and 29 healthy control subjects (range 23 to 60 years old) participated in the study. To evaluate the effects of aging, both the OSAS patients and the controls were divided into two age groups: younger (<45 years) and older (≥45 years). Amplitudes and latencies of N100, P200, N200 and P300 responses to oddball target stimuli were analyzed by repeated measures analyses of variance (ANOVA). Statistical analyses indicate that the P300 amplitudes were lower (P < 0.001), and P300 latencies were longer (P < 0.001) in OSAS patients. However, AERPs when analyzed according to age groups: P300 latencies were significantly longer in both younger and older OSAS patients (P < 0.05) but P300 amplitudes were not different in older OSAS patients compared to controls (P > 0.05). Our results suggest that negative effects of OSAS on cognitive functions could be observed with event-related brain responses. Changes in the P300 latencies are more robust evidence than other AERP components in evaluating cognitive deficits in OSAS patients.
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