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.

Anterior cingulate cortex involved in social food-foraging decision-making strategies of rats.

INTRODUCTION: Decision making as a complex cognitive process involves assessing risk, reward, and costs. Typically, it has been studied in nonsocial contexts. We have developed a novel laboratory model used with rodents to detect food-foraging decision-making strategies in different social settings. However, the brain regions that mediate these behaviors are not well identified. Substantial evidence shows that the anterior cingulate cortex (ACC) participates in evaluation of social information and in decision making. METHODS: In this study, we investigated the effect of bilateral lesions in the ACC on established behaviors. Kainic acid (KA) was administered bilaterally to induce ACC lesions, and saline microinjection into the ACC was used in the sham group. RESULTS: In contrast to the sham-lesioned animals, when faced with the choice of foraging under a social context, rats with ACC lesions preferred foraging for the less desirable food. Moreover, in these situations, the total amount of food foraged by the ACC-lesioned group was less than the amount foraged by the sham group. Notably, neither social interactions nor social agonistic behaviors were affected by ACC lesions. CONCLUSIONS: These data suggest that the ACC is a key region underlying neural processing of social decision-making, specifically tending to compete for foraging high predictive reward food.

Lipolysaccharide-Induced Neuroinflammation Is Associated with Alzheimer-Like Amyloidogenic Axonal Pathology and Dendritic Degeneration in Rats.

Chronic neuroinflammation is thought to play an etiological role in Alzheimer's disease (AD), which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatiotemporal link between neuritic and amyloid pathology, with the obligatory enzyme for ß-amyloid (Aß) production, namely ß-secretase-1 (BACE1), is overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble Aß in these genetically modified animals. Here we explored the occurrence of the AD-like axonal and dendritic pathology in adult rat brain affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated the ipsilateral hippocampal lysates in the LPS treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased ß-amyloid precursor protein and Aß antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.

Somal and dendritic development of human CA3 pyramidal neurons from midgestation to middle childhood: a quantitative Golgi study.

The CA3 area serves a key relay on the tri-synaptic loop of the hippocampal formation which supports multiple forms of mnemonic processing, especially spatial learning and memory. To date, morphometric data about human CA3 pyramidal neurons are relatively rare, with little information available for their pre- and postnatal development. Herein, we report a set of developmental trajectory data, including somal growth, dendritic elongation and branching, and spine formation, of human CA3 pyramidal neurons from midgestation stage to middle childhood. Golgi-impregnated CA3 pyramidal neurons in fetuses at 19, 20, 26, 35, and 38 weeks of gestation (GW) and a child at 8 years of age (Y) were analyzed by Neurolucida morphometry. Somal size of the impregnated CA3 cells increased age-dependently among the cases. The length of the apical and basal dendrites of these neurons increased between 26 GW to 38 GW, and appeared to remain stable afterward until 8 Y. Dendritic branching points increased from 26 GW to 38 GW, with that on the apical dendrites slightly reduced at 8 Y. Spine density on the apical and basal dendrites increased progressively from 26 GW to 8 Y. These data suggest that somal growth and dendritic arborization of human CA3 pyramidal neurons occur largely during the second to third trimester. Spine development and likely synaptogenesis on CA3 pyramidal cells progress during the third prenatal trimester and may continue throughout childhood.

Prenatal expression of purinergic receptor P2X3 in human dorsal root ganglion.

The dorsal root ganglion (DRG) is consisted of neurons that relay multiple types of spinal sensory stimuli to the central nervous system. Several neuroactive molecules may be involved in sensory modulation especially pain processing at the DRG, including the purinergic receptor P2X3 and calcitonin-gene-related peptide (CGRP). P2X3 receptor has been considered a promising pharmaceutical target for the development of new pain medicine. Currently, litter is known about the expression of P2X3 in the human DRG. The present study characterized the localization of P2X3 in prenatal human DRG obtained from fetuses at 4-8 gestational months, by comparing to CGRP expression as well as binding pattern of isolectin-B4 (IB4), a marker of small DRG neurons presumably relevant to nociception. P2X3 immunoreactivity (IR) appeared in most neuron-like perikarya, with their numerical density reduced during the gestational period studied. P2X3 IR was co-labeled very commonly with IB4 binding and infrequently with CGRP IR and was not colocalized with IR for the gliocyte marker glutamine synthetase. Together, the data show an early and broad expression of P2X3 in prenatal human DRG neurons, pointing to a biological role of purinergic signaling during the development of spinal sensory system.

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.