Neuroscience
-
Comparative Study
Differential regulation of corticosteroid receptors by monoamine neurotransmitters and antidepressant drugs in primary hippocampal culture.
Hyperactivity of the hypothalamic-pituitary-adrenal axis is a characteristic feature of depressive illness. The centrally located corticosteroid receptors, the glucocorticoid and mineralocorticoid receptors, are thought to be important modulators of this axis and changes in the levels of these receptors, particularly in the hippocampus, may underlie the hyperactivity observed. Various antidepressant drugs increase hippocampal mineralocorticoid and glucocorticoid receptor levels in vivo. ⋯ However, glucocorticoid receptor induction by fluoxetine or amitriptyline was not blocked by WAY 100635 or propanolol. These results show that 5HT, NA and antidepressants act directly but via distinct mechanisms on hippocampal neurones to regulate mineralocorticoid and glucocorticoid receptor expression. Thusly, manipulation of neurotransmitter or antidepressant levels in the brain may aid in reversing hypothalamic-pituitary-adrenal axis hyperactivity by restoring hippocampal corticosteroid receptor balance.
-
Na(+) currents were recorded using patch-clamp techniques from small-diameter (<25 micrometers) dorsal root ganglion neurons, cultured from adult rats (>150 g). Late Na(+) currents maintained throughout long-duration voltage-clamp steps (>/=200 ms) were of two types: a low-threshold, tetrodotoxin-sensitive (TTX-s) current that was largely blocked by 200 nM TTX, and a high-threshold, TTX-resistant (TTX-r) current. TTX-s late current was found in approximately 28% (10/36) of small-diameter neurons and was recorded only in neurons exhibiting TTX-s transient current. ⋯ We suggest that TTX-s late sodium current results from channel openings different from those generating transient current. As in large-diameter sensory neurons, TTX-s channels generating late openings may play a key role in controlling membrane excitability. In contrast, a single population of high-threshold TTX-r channels may account for both transient and late TTX-r currents.
-
We used kainic acid in rats as an animal model of temporal lobe epilepsy, and studied the synaptic transmission in hippocampal subfield CA1 of urethane-anesthetized rats in vivo. Dendritic currents were revealed by field potential mapping, using a single micropipette or a 16-channel silicon probe, followed by current source density analysis. We found that the population excitatory postsynaptic potentials in the basal dendrites and distal apical dendrites of CA1 were increased in kainate-treated as compared with control rats following paired-pulse, but not single-pulse, stimulation of CA3b or medial perforant path. ⋯ The bicuculline-induced excitation was mainly blocked by non-N-methyl-D-aspartate receptor antagonists. We conclude that kainate seizures induced disinhibition in CA1 that unveiled excitation at the basal and distal apical dendrites, resulting in enhancement of the direct entorhinal cortex to CA1 input and reverberations via the hippocampo-entorhinal loop. These changes in the output of the hippocampus from CA1 are likely detrimental to the behavioral functions of the hippocampus and they may contribute to increased seizure susceptibility after kainate seizures.
-
Cell surface glycoconjugates are thought to mediate cell-cell recognition and to play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of glyco-chains with an N-acetylgalactosamine (GalNAc) residue at the non-reducing termini (GalNAc-S) such as GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer (GM2) ganglioside, its oligosaccharide portion, GalNAcbeta4Galbeta4GlcCer (Gg(3)) Cer, GalNAcalpha3GalNAcbeta3Galalpha4Galbeta4GlcCer (Gb(5)) Cer (Forssman hapten) and alpha1-4 linked oligomers of GalNAc, induced a rapid and transient activation of cAMP-dependent protein kinase (PKA) in subplasmalemma. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary cultured hippocampal neurons, but not in glial cells. ⋯ These results suggest that extracellular GalNAc-S serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of PKA followed by cdc42 up-regulation via a cell surface receptor-like component. Filopodia formation induced by GalNAc-S may have a physiological relevance because long-term exposure to GalNAc-S enhanced F-actin-rich dendrite generation of primary cultured hippocampal neurons, and PKA-dependent dendritic outgrowth and branch formation of primary cultured cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. These findings provide evidence for a novel GalNAc/PKA-signaling cascade in regulating some neuronal maturation.
-
The suprachiasmatic nuclei (SCN) contain the main clock of the mammalian circadian system. The endogenous oscillation machinery involves interactive positive and negative transcriptional and posttranslational feedback loops involving the clock genes Per1, Per2, Per3, Clock, Bmal1, Cry1 and Cry2. The SCN endogenous oscillation is entrained to 24 h by the light/dark cycle. ⋯ Results showed that melatonin injection affected none of the mRNA expression pattern during the first circadian night. Per1, Per3, Bmal1 and AVP expression patterns were, however, significantly but differentially affected, during the second subjective night after the melatonin injection. The present results strongly suggest that the immediate phase shifting effect of melatonin on the SCN molecular loop implicates rather post-translational than transcriptional mechanisms.