Neuroscience
-
We reported previously that amoeboid microglial cells (AMC) in the developing brain exhibited endothelins (ETs) expression which diminished with advancing age and was undetected in microglia in the more mature brain. This study sought to explore if microglia in the adult would be induced to express ETs in altered conditions. By immunofluorescence microscopy, ETs and endothelin (ET)-B receptor were undetected in microglial cells in sham-operated and normal control rats. ⋯ ET-1, ET-3 and ET-B receptor were also localized in reactive astrocytes along with some oligodendrocytes. We conclude that activated microglia together with other glial cells in the marginal zone after MCAO are the main cellular source of ETs that may be involved in regulation of vascular constriction and glial chemokines/cytokines production. However, dissecting the role of individual component of the endothelin system in the various glial cells, notably activated microglia, would be vital in designing of an effective therapeutic strategy for clinical treatment of stroke in which microglial cells have been implicated.
-
Striatal neurons are known to express GABA(A) receptor subunits that underlie both phasic and tonic inhibition. Striatal projection neurons, or medium spiny neurons (MSNs), are divided into two classes: MSNs containing the dopamine D1 receptor (D1-MSNs) form the direct pathway to the substantia nigra and facilitate movement while MSNs expressing the dopamine D2 receptor (D2-MSNs) form the pallidal pathway that inhibits movement. Consequently, modulating inhibition in distinct classes of MSNs will differentially impact downstream network activity and motor behavior. ⋯ Compared to wild-type, MSNs from adult mice lacking the GABA(A)R delta subunit (Gabrd(-/-) mice) had both decreased tonic GABA currents and reduced survival following an in vitro excitotoxic challenge with quinolinic acid. Furthermore, muscimol-induced tonic GABA currents were accompanied by reduced acute swelling of striatal neurons after exposure to NMDA in WT mice but not in Gabrd(-/-) mice. Our data are consistent with a role for tonic inhibition mediated by GABA(A)R delta subunits in neuroprotection against excitotoxic insults in the adult striatum.
-
While it is well established that exercise can improve cognitive performance, it is unclear how long these benefits endure after exercise has ended. Accordingly, the effects of voluntary exercise on cognitive function and brain-derived neurotrophic factor (BDNF) protein levels, a major player in the mechanisms governing the dynamics of memory formation and storage, were assessed immediately after a 3-week running period, or after a 1-week or 2-week delay following the exercise period. All exercised mice showed improved performance on the radial arm water maze relative to sedentary animals. ⋯ Assessment of the time course of hippocampal BDNF availability following exercise revealed significant elevations of BDNF immediately after the exercise period (186% of sedentary levels) and at 1 and 2 weeks after exercise ended, with levels returning to baseline by 3-4 weeks. BDNF protein levels showed a positive correlation with cognitive improvement in radial water maze training and with memory performance on day 4, supporting the idea that BDNF availability contributes to the time-dependent cognitive benefits of exercise revealed in this study. Overall, this novel approach assessing the temporal endurance of cognitive and biochemical effects of exercise unveils new concepts in the exercise-learning field, and reveals that beneficial effects of exercise on brain plasticity continue to evolve even after exercise has ended.
-
Dopamine/cAMP signaling has been reported to mediate behavioral responses related to drug addiction. It also modulates the plasticity and firing properties of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), although the effects of cAMP signaling on the resting membrane potential (RMP) of MSNs has not been specifically defined. In this study, activation of dopamine D1-like receptors (D1Rs) by SKF-38393 elicited membrane depolarization and inward currents in MSNs from the NAc core of 14-17 day-old mice. ⋯ Collectively, these data suggest that stimulation of postsynaptic D1Rs in MSNs of the NAc core causes membrane depolarization by inhibiting Kir currents. This effect is mediated by AC/cAMP signaling but it is independent on PKA, PKC, Epac and CNG channel activation, suggesting that it may stem from cAMP's direct interaction with Kir channels. D1R/cAMP-mediated excitatory effects may influence the generation of output signals from MSNs by facilitating their transition from the quiescent down-state to the functionally active up-state.
-
The sigma-1 receptor regulates various ion channel activity and possesses protein chaperone function. Using an antibody against the full sequence of the sigma-1 receptor we detected immunostaining in wild type but not in knockout mice. The receptor was found primarily in motoneurons localized to the brainstem and spinal cord. ⋯ Ultrastructural analysis of the neurons indicates that the immunostained receptor is located close but separate from the plasma membrane, possibly in subsurface cisternae formed from the endoplasmic reticulum (ER), which are a prominent feature of cholinergic postsynaptic densities. Behavioral testing on a rotorod revealed that Sigma-1 receptor knockout mice remained on the rotorod for significantly less time (a shorter latency period) compared to the wild type mice. Together these data indicate that the sigma-1 receptor may play a role in the regulation of motor behavior.