Neuroscience journal最新文献

In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT) expression associated with low testosterone (T) levels. The objectives of this study were to establish (1) if brain SERT expression is reduced by aging and (2) if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3-5 months) and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

With an ever-increasing population of Alzheimer's disease (AD) patients worldwide, a noninvasive treatment for AD is needed. In this paper, the application of repetitive transcranial magnetic stimulus (rTMS) as a treatment for patients with probable AD is compared to the application of rTMS as a treatment for depression. Comorbidity of depression and dementia is discussed, as well as possible links between the two diseases. The possible confounding antidepressant effects of rTMS on cognitive improvements in AD patients are discussed.

Metabotropic glutamate 2/3 (mGlu2/3) receptors have emerged as potential therapeutic targets due to the ability of mGlu2/3 receptor agonists to modulate excitatory transmission at specific synapses. LY354740 and LY379268 are selective and potent mGlu2/3 receptor agonists that show both anxiolytic- and antipsychotic-like effects in animal models. We compared the efficacy of LY354740 and LY379268 in attenuating restraint-stress-induced expression of the immediate early gene c-Fos in the rat prelimbic (PrL) and infralimbic (IL) cortex. LY354740 (10 and 30 mg/kg, i.p.) showed statistically significant and dose-related attenuation of stress-induced increase in c-Fos expression, in the rat cortex. By contrast, LY379268 had no effect on restraint-stress-induced c-Fos upregulation (0.3-10 mg/kg, i.p.). Because both compounds inhibit serotonin 2A receptor (5-HT2AR)-induced c-Fos expression, we hypothesize that LY354740 and LY379268 have different in vivo properties and that 5-HT2AR activation and restraint stress induce c-Fos through distinct mechanisms.

The roles of integrin subunits and intracellular molecules in regulating the migration and neuritogenesis of neurons isolated from 16.5 gestation days rat fetal cortices were examined using in vitro assays. Results showed that laminin supported the migration of fetal cortical neurons better than fibronectin and that the fetal cortical neurons migrated on laminin using β1 and α3 integrin subunits which make up the α3β1 integrin receptor. On fibronectin, the migration was mediated by β1 integrin subunit. Perturbation of src kinase, phospholipase C, or protein kinase C activity, inhibition of IP3 receptor mediated calcium release, or chelation of intracellular calcium inhibited both migration and neuritogenesis, whereas inhibition of growth factor signaling via MEK inhibited only the neuritogenesis. The detection of α1 and α9 transcripts suggested that the migration of fetal cortical neurons may also be mediated by α1β1 and α9β1 integrin receptors. Results showed that calcium may regulate migration and neuritogenesis by maintaining optimum levels of microtubules in the fetal cortical neurons. It is concluded that the fetal cortical neurons are fully equipped with the integrin signaling cascade required for their migration and neuritogenesis, whereas crosstalk between the integrin and growth-factor signaling regulate only the neuritogenesis.

Visual evoked potentials is an important visual electrophysiological tool which has been used for the evaluation of visual field defects in primary open-angle glaucoma and is an appropriate objective measure of optic nerve function. Significant correlations between the magnitude of the VEP parameters and MD of Humphrey static perimetry suggest that the impaired visual cortical responses observed in glaucoma patients can be revealed by both electrophysiological and psychophysical methods. In addition, the severity of global glaucomatous damage evidenced by reduction in MD could depend on the delay in neural conduction from retina to the visual cortex as revealed by the significant correlation between VEP latencies and MD which also supports the validity of the VEP testing in progression of glaucoma.

Problem Addressed. Decoding of silent vocalization would be enhanced by detecting vocalization onset. This is necessary in order to improve decoding of neural firings and thus synthesize near conversational speech in locked-in subjects implanted with brain computer interfacing devices. Methodology. Cortical recordings were obtained during attempts at inner speech in a mute and paralyzed subject (ER) implanted with a recording electrode to detect and analyze lower beta band peaks meeting the criterion of a minimum 0.2% increase in the power spectrum density (PSD). To provide supporting data, three speaking subjects were used in a similar testing paradigm using EEG signals recorded over the speech area. Results. Conspicuous lower beta band peaks were identified around the time of assumed speech onset. The correlations between single unit firings, recorded at the same time as the continuous neural signals, were found to increase after the lower beta band peaks as compared to before the peaks. Studies in the nonparalyzed control individuals suggested that the lower beta band peaks were related to the movement of the articulators of speech (tongue, jaw, and lips), not to higher order speech processes. Significance and Potential Impact. The results indicate that the onset of silent and overt speech is associated with a sharp peak in lower beta band activity-an important step in the development of a speech prosthesis. This raises the possibility of using these peaks in online applications to assist decoding paradigms being developed to decode speech from neural signal recordings in mute humans.

Chronic stress has been shown to impact learning, but studies have been sparse or nonexistent examining sex or task differences. We examined the effects of sex and chronic stress on instrumental learning in adult rats. Rats were tested in an aversive paradigm with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained across the stress period for males (-7%, P ≤ .05) and females (-5%, P ≤ .05). For males, there were within-subject day-by-day differences after asymptotic transition, and all restrained males were delayed in reaching asymptotic performance. In contrast, stressed females were facilitated in appetitive and aversive-only instrumental learning but impaired during acquisition of the aversive transfer task. Males were faster than females in reaching the appetitive shaping criterion, but females were more efficient in reaching the appetitive tone-signaled criterion. Finally, an effect of task showed that while females reached aversive shaping criterion at a faster rate when they had prior appetitive learning, they were impaired in tone-signaled avoidance learning only when they had prior appetitive learning. These tasks reveal important nuances on the effect of stress and sex differences on goal-directed behavior.

This study set out to assess the neurobehavioral effects of subchronic, oral bromocriptine methanesulfonate using the open field and the Y-maze in healthy male mice. Sixty adult Swiss albino mice were assigned into three groups. Controls received normal saline, while test groups received bromocriptine methanesulfonate at 2.5 and 5 mg/kg/day, respectively, for a period of 21 days. Neurobehavioral tests were carried out on days 1 and 21 after administration. Open field assessment on day 1 after administration revealed significant increase in grooming at 2.5 and 5 mg/kg, while horizontal and vertical locomotion showed no significant changes. Day 1 also showed no significant changes in Y-maze alternation. On day 21, horizontal locomotion, rearing, and grooming were increased significantly at 2.5 and 5 mg/kg doses after administration; also, spatial memory was significantly enhanced at 2.5 mg/kg. In conclusion, the study demonstrates the ability of oral bromocriptine to affect neurobehavior in normal mice. It also suggests that there is a cumulative effect of oral bromocriptine on the behaviors studied with more changes being seen after subchronic administration rather than after a single oral dose.

Objectives. We aimed to test the hypothesis that metabolic syndrome (MetS) is significantly associated with cognitive decline (CoD) in elderly adults and further assess whether MetS and inflammation have a significant joint effect on CoD. Methods. Data (n = 2975) from the U.S. National Health and Nutrition Examination Survey (1999-2002) in participants aged ≥60 years who had Digit Symbol Substitution Tests (DSS: a standard measure of cognitive function) were studied. CoD was defined as those in the lowest quintile of DSS score. MetS was defined as having ≥3 of 5 MetS traits (large waist circumference (WC), high blood pressure (BP), elevated glucose, triglycerides, and decreased high density lipoprotein cholesterol). Results. Of 2975 participants, the prevalence of CoD (DSS score <25) was 12.1%. After adjusting covariates, individual large WC, high BP, elevated glucose level, and MetS were significantly associated with CoD in logistic regression models (P < 0.001). There was a significant dose-response relationship between an increased number of MetS traits and CoD (P < 0.001). A significant joint effect of MetS and CRP on the odds of CoD was observed. Conclusion. The study, using a nationally representative sample, extended previous studies by highlighting a significant MetS-CoD relationship and a joint effect of MetS and CRP on CoD. These novel findings add to our understanding of the association of neurometabolic disorders and cognition and have implications that may be relevant to primary care practice.

The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P < 0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P < 0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.