Developmental Brain Research最新文献

Sensory gating is the ability to filter irrelevant or redundant sensory input and is a critical function of all sensory systems that allows efficient processing of important stimuli. The present results demonstrate that a form of activity-dependent synaptic depression recently found to be involved in both cortical and behavioral olfactory sensory gating, is functional by at least the first postnatal week in the rat piriform cortex, and shares a common metabotropic glutamate receptor mechanism.

Hereditary congenital facial paresis is a rare autosomal dominantly inherited disorder, in which pathological changes in the brainstem affect the paired facial nuclei and nerves. Previously, the neuropilin-1 protein has been shown to control axon guidance and cell body position of facial motor neurons, and mice with a targeted disruption of neuropilin-1 present with developmental defects of the facial nerve nuclei. Plexin-A1 can function as a signal transducing subunit for the neuronal neuropilin receptor, and its gene is located in the linkage interval for hereditary congenital facial paresis at chromosome 3q21–q22 (MIM601471), making it an excellent candidate gene for this disorder. During mouse embryogenesis, the murine ortholog of plexin-A1 gene showed restricted spatial and temporal expression in the hindbrain, consistent with a role in cell body movement, or axonal guidance during facial nerve development. Sequence analysis of the plexin-A1 gene in patients from the 3q21–q22-linked hereditary congenital facial paresis family revealed several nucleotide changes. However, none of the nucleotide changes led to an amino acid substitution, and reverse transcriptase polymerase chain reaction analysis did not detect aberrant RNA processing. We therefore conclude that it is highly unlikely that Plexin-A1 is involved in the pathogenicity of hereditary congenital facial paresis.

Cultures of rat mesencephalic precursors treated with interleukin-1β or angiotensin II contained significantly more dopaminergic neurons than controls. However, simultaneous treatment with angiotensin II and interleukin-1β did not induce any further increase. Treatment with the angiotensin type-2 receptor antagonist PD 123319 precluded both the angiotensin- and the interleukin-induced increase. The present results indicate that angiotensin type-2 receptors and interleukin-1 cooperate to induce the dopaminergic phenotype.

cGMP synthesis in cholinergic neurons of the basal forebrain, the caudate putamen, and the tegmento-pedunculopontine nucleus of the rat was studied during development after birth at P1, P4, P10, and P21, in the adult, and during aging. NO-mediated cGMP synthesis in these neurons was studied using the approach of in vitro incubation of brain slices in combination with cGMP-immunocytochemistry. The percentage of NO-responsive, cGMP-synthesizing cholinergic cells in the septum and diagonal band of Broca decreased from 75% to 6% in adult animals and to 2% in aged ones. In the caudate putamen, this decrease was from 81% to 21% in adult and 11% in aged animals. Cholinergic cells of the tegmento-pedunculopontine nucleus were unresponsive to NO and never showed cGMP-immunoreactivity. In addition, it was observed that the amount of NO-responsive, cGMP-synthesizing cholinergic fibers in the hippocampus declined in parallel with the maturation of the septal–hippocampal cholinergic pathway, whereas in the caudate putamen, this colocalization became complete 2 weeks after birth. It is concluded that the property of NO-mediated cGMP synthesis in the cholinergic nuclei of the forebrain is developmentally regulated after birth and that NO-cGMP signal transduction has a role in establishing cholinergic neuronal connections in the hippocampus and caudate putamen.

The inhibitory effects of morphine and α₂-adrenoceptor agonists on slow ventral root potentials (slow VRP) following ipsilateral dorsal root stimulation in neonatal rat spinal cord were compared with the analgesic effects of these drugs on formalin and capsaicin tests in neonatal rats. Morphine, (D-Phe², D-Pen⁵)-enkephalin (DPDPE), dexmedetomidine, clonidine and xylazine showed concentration-related inhibition of slow VRP. The order of potency was dexmedetomidine  > morphine = DPDPE > clonidine > xylazine. The inhibitory effects of opioid agonists and α₂-adrenoceptor agonists were abolished by naloxone, an opioid antagonist, and atipamezole, an α₂-adrenoceptor antagonist, respectively. There was no cross antagonism. Morphine, dexmedetomidine and xylazine dose-dependently inhibited body movement induced by formalin or capsaicin. The order of potency was dexmedetomidine > morphine > xylazine. Although morphine and dexmedetomidine inhibited formalin- and capsaicin-induced body movement in the same dose range, xylazine inhibited formalin-induced body movement at lower concentrations than capsaicin-induced one. The inhibitory potency for slow VRP by these drugs seems to be correlated with that for capsaicin-induced body movement but not that for formalin-induced one. Dexmedetomidine and morphine in combination inhibited slow VRP and body movement induced by capsaicin in an additive manner. It is suggested that the antinociceptive effects of dexmedetomidine and morphine but not xylazine on the capsaicin test are mainly due to spinal effects and that there is no synergistic interaction between dexmedetomidine and morphine in the neonatal rat.

Maternal care in the rabbit is restricted to a single 3- to 5-min period of nursing each day. One to three hours prior to the arrival of the mother, pups exhibit anticipatory behavioral arousal and elevation of core body temperature. In rodents, the hypothalamic–pituitary–adrenal axis is quiescent and levels of the adrenal hormone, corticosterone (CORT), are stable and extremely low during the first days of life, which are known collectively as the stress-hyporesponsive period (SHRP). It has been proposed that the rabbit also has an SHRP. However, we decided to examine CORT changes associated with the daily nursing bout, since behavioral arousal, core body temperature, and CORT are elevated prior to the onset of feeding in many other species. We scheduled the nursing bout at 1000 h and analyzed CORT concentration using RIA in pups sampled at various intervals after suckling. CORT levels showed a circadian variation that peaked at the time of the daily nursing bout. After nursing, values steadily decreased to a nadir at 2200 h and then rose again in advance of the next scheduled nursing. The three-fold difference between the highest (1000 h) and the lowest (2200 h) CORT values suggests that either the SHRP does not exist in rabbit pups or else it has properties that differ from those described for rodents. Unlike rodents, rabbit pups show a circadian secretion of CORT synchronized to the scheduled nursing bout.

Mannose-6-phosphate receptors (MPRs) play a role in the selective transport of macromolecules bearing mannose-6-phosphate residue to lysosomes. To date, two types of MPRs have been described in most of cells and tissues: the cation-dependent (CD-MPR) and cation-independent mannose-6-phosphate receptor (CI-MPR). In order to elucidate their possible role in the central nervous system, the expression and binding properties of both MPRs were studied in rat brain along perinatal development. It was observed that the expression of CI-MPR decreases progressively from fetuses to adults, while the CD-MPR increases around the 10th day of birth, and maintains these values up to adulthood. Binding assays showed differences in the B_max and K_D values between the ages studied, and they did not correlate with the expression levels of both MPRs. Variations in lysosomal enzyme activities and expression of phosphomannosylated ligands during development correlated more with CD-MPR than with CI-MPR expression. These results suggest that both receptors play a different role in rat brain during perinatal development, being CD-MPR mostly involved in lysosome maturation.