Neuroscience
-
Previous research has demonstrated antidepressant-like effects in rodents upon intracerebral inhibition of histone deacetylases (HDACs). Such effects have been reported for local HDAC inhibition in the nucleus accumbens, hippocampus, and amygdala. ⋯ Here we show that local infusion of the highly selective HDAC inhibitor, MS-275, into the medial prefrontal cortex exerts robust antidepressant-like effects in the chronic social defeat stress paradigm in mice. These findings provide further impetus for the assessment of HDAC inhibitors for the treatment of depression.
-
Exposure to early-life inflammation results in time-of-challenge-dependent changes in both brain and behavior. The consequences of this neural and behavioral reprogramming are most often reported in adulthood. However, the trajectory for the expression of these various changes is not well delineated, particularly between the juvenile and adult phases of development. ⋯ Moreover, these males had decreased prefrontal cortex levels of glutathione at P40, which was normalized in adult animals. Notably, EE appeared to offer some protection against the consequences of inflammation on juvenile social behavior and fully prevented reduced glutathione levels in the juvenile prefrontal cortex. Combined, these time-dependent effects provide evidence that early-life inflammation interacts with other developmental variables, specifically puberty and EE, in the expression (and prevention) of select behavioral and molecular programs.
-
Several studies reveal that the beneficial effects of exercise interventions are dependent on the progression of Alzheimer's disease (AD). We have previously shown that long-term treadmill exercise begun before the onset of β-amyloid (Aβ) pathology prevents the deficits of cognition and long-term potentiation (LTP) in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice (8 months of age) paralleled by the reduction of soluble Aβ levels and Aβ deposition in the hippocampus. ⋯ In addition, exercise-induced enhancement of synaptic plasticity was accompanied by a significant reduction of soluble Aβ levels rather than Aβ plaque deposition. Therefore, the investigation demonstrates that long-term treadmill exercise has beneficial effects on cognition and synaptic plasticity even when the brain has developed Aβ deposition, and changes in soluble Aβ levels rather than Aβ plaque deposition may contribute to exercise-induced benefits.
-
Traumatic brain injury (TBI) is associated with a risk of neurodegenerative disease. Some suggest a link between TBI and motor neuron disease (MND), including amyotrophic lateral sclerosis (ALS). To investigate the potential mechanisms linking TBI to MND, we measured motor function and neuropathology following mild-TBI in wild-type and a transgenic model of ALS, G93A mutant mice. ⋯ Markers of inflammation (cell edema, astrogliosis and microgliosis) were detected at 24 and 72h in the brain and spinal cord in wild-type and G93A mice. Levels of F2-isoprostanes, a marker of oxidative stress, were increased in the spinal cord 24h post mild-TBI in wild-type mice but were not affected by TBI in G93A mice. In summary, our data demonstrate that mild-TBI induces inflammation and oxidative stress and negatively impacts muscle denervation and motor performance, suggesting mild-TBI can potentiate motor neuron pathology and influence the development of MND in mice.
-
A common scientific strategy toward understanding consciousness is to study neural correlates of consciousness (NCC) for a particular conscious percept. This can be done by contrasting conditions in which subjects are aware and unaware of a particular visual stimulus. However, recent findings have been contradictory and this approach appears not to reveal only the NCC, but also the prerequisites or consequences of consciousness. ⋯ Results indicate that trials where subjects reported to have seen the stimulus are associated with a more pronounced P300. Hence, the present data support the theories which claim that P300 is a marker of conscious perception. However, an earlier component, visual awareness negativity also tracks conscious perception reliably so that the P300 need not be the earliest correlate of conscious perception.