Synaptic development of layer V pyramidal neurons in the prenatal human prefrontal neocortex: a Neurolucida-aided Golgi study.

The prefrontal neocortex is involved in many high cognitive functions in humans. Deficits in neuronal and neurocircuitry development in this part of the cerebrum have been associated with various neuropsychiatric disorders in adolescents and adults. There are currently little available data regarding prenatal dendrite and spine formation on projecting neurons in the human prefrontal neocortex. Previous studies have demonstrated that Golgi silver staining can identify neurons in the frontal lobe and visual cortex in human embryos. In the present study, five fetal brains, at 19, 20, 26, 35, and 38 gestational weeks, were obtained via the body donation program at Xiangya School of Medicine, Central South University, China. Golgi-stained pyramidal neurons in layer V of Brodmann area 46 in fetuses were quantitatively analyzed using the Neurolucida morphometry system. Results revealed that somal size, total dendritic length, and branching points of these neurons increased from 26 to 38 gestational weeks. There was also a large increase in dendritic spines from 35 to 38 gestational weeks. These findings indicate that, in the human prefrontal neocortex, dendritic growth in layer V pyramidal neurons occurs rapidly during the third trimester of gestation. The use of human fetal brain tissue was approved by the Animal Ethics Committee of Xiangya School of Medicine, Central South University, China (approval No. 2011-045) on April 5, 2011.

Formalin-induced increase in P2X(3) receptor expression in dorsal root ganglia: implications for nociception.

1. ATP-gated P2X receptors in nociceptive sensory neurons participate in the transmission of pain signals from the periphery to the spinal cord. The effect of formalin on the expression of P2X(3) receptors in dorsal root ganglia (DRG) was characterized using molecular and immunological approaches and the patch-clamp technique. 2. Adult Sprague-Dawley rats were injected with 100 microL of 5% formalin in the planar surface of the hindpaw and were killed 30 min and 1, 3, 6, 12, 24 and 48 h later for in vitro analyses. The expression and distribution of P2X(3) receptors in the lumbar spinal cord and in L5/L6 DRG were examined; 24 and 48 h after formalin injection, currents in neurons were examined using whole-cell patch-clamp recording. 3. Western blots showed that anti-P2X(3) antibody recognized a major monomer of approximately 64 kDa in DRG. Immunoreactivity for P2X(3) receptors was detected predominantly in the cytoplasm and plasma membrane of small (< 25 microm) and middle-sized (25-50 microm) DRG neurons. Expression of the P2X(3) transcript in the DRG was unchanged 30 min and 1 h after formalin injection, but increased after 12 h. There was no distinct change in P2X(3) immunostaining of the spinal cord lamina at 30 min or 1 h after injection, but after 24 h P2X(3) labelling increased. At 24 h after the formalin injection, currents in isolated small and middle-sized DRG neurons were increased by 1 micromol/L alpha,beta-methylene-ATP. These currents were completely inhibited by 1 micromol/L A-317491, a potent and selective P2X(3) receptor antagonist. 4. These data suggest that formalin injection leads to early upregulation of P2X(3) expression in the spinal cord and DRG and that this may be one of the mechanisms giving rise to nociception.

[Expression of brain-derived neurotrophic factor in hippocampus of ovariectomized mouse].

OBJECTIVE: To explore the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus after ovariectomy in mice. METHODS: BDNF levels were detected by immunohistochemistry combined image analysis in hippocampal CA regions and dentate gyrus of ovariectomized mice. RESULTS: The expression of BDNF in hippocampus of mice decreased significantly after the ovariectomy after 4 days. The recovery BDNF expression started 14 days after the ovariectomy and after 28 days, the expression of BDNF in hippocampus recovered to the normal level. CONCLUSION: The decrease of estrogen in ovariectomized mice can weaken the expression of BDNF in hippocampus during the early stage.

Impaired long-term potentiation in c-Jun N-terminal kinase 2-deficient mice.

c-Jun N-terminal kinases (JNKs) are thought to be involved in regulating synaptic plasticity. We therefore investigated the specific role of JNK2 in modulating long-term potentiation (LTP) in hippocampus during development, using JNK2-deficient mice. The morphological structure and the numbers of both NeuN, a specific neuronal marker, and GABA-positive neurons in the hippocampal areas were similar in wild-type and Jnk2(-/-) mice. Western blot analysis revealed that JNK2 expression was higher and stable at 1 and 3 months of age, but JNK1 levels were lower at 1 month of age and almost undetectable in 3-month-old wild-type mice. In contrast to wild-type mice, there was a significant increase in JNK1 expression in JNK2 mutant mice, especially at 1 month of age. Electrophysiological studies demonstrated that LTP was impaired in both the CA1 and CA3 regions in 1-month-old, but not in adult, Jnk2(-/-) mice, probably owing to decreased presynaptic neurotransmitter release. Moreover, late-phase LTP, but not early-phase LTP, was impaired in the Jnk2(-/-) adult mice, suggesting that JNK2 plays a role in transforming early LTP to late LTP. Together, the data highlight the specific role of JNK2 in hippocampal synaptic plasticity during development.