Neuroscience
-
We tested the hypothesis that decreasing the control level of O2 from 95% to 40% reduces tissue partial pressure of oxygen (pO2), decreases extracellular nitric oxide (NO) and decreases intracellular superoxide (O2(-)) while maintaining viability in caudal solitary complex (cSC) neurons in slices (∼300-400 μm; neonatal rat P2-22; 34-37°C). We also tested the hypothesis that normobaric hyperoxia is a general stimulant of cSC neurons, including CO2-excited neurons. Whole-cell recordings of cSC neurons maintained in 40% O2 were comparable to recordings made in 95% O2 in duration and quality. ⋯ Likewise, a higher incidence of CO2-inhibited and lower incidence of CO2-excited neurons were observed in 85-95% O2. 82% of O2-excited neurons were also CO2-chemosensitive; CO2-excited (86%) and CO2-inhibited neurons (84%) were equally stimulated by hyperoxia. Our findings demonstrate that chronic (hours) and acute (minutes) exposure to hyperoxia stimulates firing rate in the majority of cSC neurons, most of which are also CO2 chemosensitive. Our findings support the hypothesis that recurring exposures to acute hyperoxia and hyperoxic reoxygenation-a repeating surge in tissue pO2-activate redox and nitrosative signaling mechanisms in CO2-chemosensitive neurons that alter expression of CO2 chemosensitivity (e.g., increased expression of CO2-inhibition) compared to sustained hyperoxia (85-95% O2).
-
Lateral hypothalamic (LH) stimulation produces antinociception in female rats in acute, nociceptive pain. Whether this effect occurs in neuropathic pain or whether male-female sex differences exist is unknown. We examined the effect of LH stimulation in male and female rats using conditions of nociceptive and neuropathic pain. ⋯ However, nociceptive females responded only to the 500-nmol dose, while nociceptive males responded to all doses (p<0.05). For right PWL, only nociceptive males showed a significant carbachol dose response. These findings are suggestive that LH stimulation produces antinociception in male and female rats in both nociceptive and neuropathic pain, but dose response differences exist based on sex and pain condition.
-
Ibuprofen is a widely used nonsteroidal anti-inflammatory drug that reportedly reduces the risk of Alzheimer's disease (AD) development. The anti-inflammatory effect of ibuprofen occurred via inhibition of cyclooxygenases and anti-amyloidogenesis through modulation of γ-secretase. Presenilin 1 and 2 conditional double-knockout (cDKO) mice exhibited age-dependent memory impairment and forebrain degeneration without elevation of amyloid β deposition. ⋯ Ibuprofen was more effective on six-month-old than on three-month-old cDKO mice. Biochemical analysis demonstrated that the effects of ibuprofen on glial fibrillary acidic protein and CD68 expression levels were uneven in different brain regions of cDKO mice and that age also influenced such effects. Tau hyperphosphorylation and the cleavage of caspase-3 decreased after ibuprofen treatment, and this effect was more significant in the older than the younger group of mice, which was consistent with the results of behavioral tests.
-
Caffeine is the psychostimulant most consumed worldwide but concerns arise about the growing intake of caffeine-containing drinks by adolescents since the effects of caffeine on cognitive functions and neurochemical aspects of late brain maturation during adolescence are poorly known. We now studied the behavioral impact in adolescent male rats of regular caffeine intake at low (0.1mg/mL), moderate (0.3mg/mL) and moderate/high (1.0mg/mL) doses only during their active period (from 7:00 P. M. to 7:00 A. ⋯ All tested doses of caffeine decreased the density of glial fibrillary acidic protein and synaptosomal-associated protein-25, but failed to modify neuron-specific nuclear protein immunoreactivity in the hippocampus and cerebral cortex. Caffeine (0.3-1mg/mL) increased the density of brain-derived neurotrophic factor (BDNF) and proBDNF density as well as adenosine A1 receptor density in the hippocampus, whereas the higher dose of caffeine (1mg/mL) increased the density of proBDNF and BDNF and decreased A1 receptor density in the cerebral cortex. These findings document an impact of caffeine consumption in adolescent rats with a dual impact on anxiety and recognition memory, associated with changes in BDNF levels and decreases of astrocytic and nerve terminal markers without overt neuronal damage in hippocampal and cortical regions.
-
Head direction (HD) cells have been identified in a number of limbic system structures. These cells encode the animal's perceived directional heading in the horizontal plane and are dependent on an intact vestibular system. ⋯ These mechanisms are: (1) the ascending vestibular signal is generated by more than just vestibular-only neurons, (2) not all vestibular-only neurons contributing to the HD pathway have firing rates that are attenuated by active head turns, (3) the ascending pathway may be spared from the affects of the attenuation in that the HD system receives information from other vestibular brainstem sites that do not include vestibular-only cells, and (4) the ascending signal is affected by the inhibited vestibular signal during an active head turn, but the HD circuit compensates and uses the altered signal to accurately update the current HD. Future studies will be needed to decipher which of these possibilities is correct.