Granule cells (GCs) in the dentate gyrus are generated mainly postnatally. Between embryonic day 10 and 14, neural precursors migrate from the primary dentate matrix to the dentate gyrus where they differentiate into neurons. Neurogenesis reaches a peak at the end of the first postnatal week and it is completed at the end of the first postnatal month. This process continues at a reduced rate throughout life. Interestingly, immediately after birth, GCs exhibit a clear GABAergic phenotype. Only later they integrate the classical glutamatergic trisynaptic hippocampal circuit. Here, whole patch clamp recordings, in current clamp mode, were performed from immature GCs, intracellularly loaded with biocytin (in hippocampal slices from P0-P3 old rats) in order to compare their morphological characteristics with their electrophysiological properties. The vast majority of GCs were very immature with small somata, few dendritic branches terminating with small varicosities and growth cones. In spite of their immaturity their axons reached often the CA3 area. Immature GCs generated, upon membrane depolarization, either rudimentary sodium spikes or more clear overshooting action potentials that fired repetitively. They exhibited also low threshold calcium spikes. In addition, most spiking neurons showed spontaneous synchronized network activity, reminiscent of giant depolarizing potentials (GDPs) generated in the hippocampus by the synergistic action of glutamate and GABA, both depolarizing and excitatory. This early synchronized activity, absent during adult neurogenesis, may play a crucial role in the refinement of local neuronal circuits within the developing dentate gyrus.

The architecture of neocortical projection neurons is subject of a complex gene control. Here we demonstrated that Foxg1, a transcription factor gene which patterns the early rostral brain and sets the pace of telencephalic neuronogenesis, specifically stimulates dendrite elongation. This phenomenon occurs in vivo like in vitro, and it is detectable even upon moderate changes of Foxg1 expression levels. We found that Foxg1 acts by stimulating Hes1, which in turn upregulates pCreb1, a well-known pro-dendritogenic effector, and downregulates Syt and Ndr1, namely two established antagonizers of dendrite elongation. Moreover, Foxg1-driven pCreb1 upregulation requires PKA and AKT, and correlates with reduced PP1 and PP2A phosphatase activity. These findings contribute to clarify normal neurodevelopmental and activity-related regulation of neuritogenesis. They further suggest that an abnormal sizing of the dendritic tree of neocortical projection neurons may occur in West and Rett syndrome patients with anomalous FOXG1 allele dosages and contribute to their neurolopathological profiles.

Human leukocyte antigen (HLA) genotyping displays the particular characteristics of HLA alleles and haplotype frequencies in each population. Although it is considered the current gold standard for HLA typing, high-resolution sequence-based HLA typing is currently unavailable in Kinh Vietnamese populations. In this study, high-resolution sequence-based HLA typing (3-field) was performed using an amplicon-based next-generation sequencing platform to identify the HLA-A, -B, -C, -DRB1, and -DQB1 alleles of 101 unrelated healthy Kinh Vietnamese individuals from southern Vietnam. A total of 28 HLA-A, 41 HLA-B, 21 HLA-C, 26 HLA-DRB1, and 25 HLA-DQB1 alleles were identified. The most frequently occurring HLA alleles were A^∗11:01:01, B^∗15:02:01, C^∗07:02:01, DRB1^∗12:02:01, and DQB1^∗03:01:01. Haplotype calculation showed that A^∗29:01:01∼B^∗07:05:01, DRB1^∗12:02:01∼DQB1^∗3:01:01, A^∗29:01:01∼C^∗15:05:02∼B^∗07:05:01, A^∗33:03:01∼B^∗58:01:01∼DRB1^∗03:01:01, and A^∗29:01:01∼C^∗15:05:02∼B^∗07:05:01∼DRB1^∗10:01:01∼DQB1^∗05:01:01 were the most common haplotypes in the southern Kinh Vietnamese population. Allele distribution and haplotype analyses demonstrated that the Vietnamese population shares HLA features with South-East Asians but retains unique characteristics. Data from this study will be potentially applicable in medicine and anthropology.

Objective: The aim of this study was to investigate risk factors for cutaneous adverse reactions (CARs) in Kinh Vietnamese.Methods: All patients were prospectively recruited in Ho Chi Minh City. Presence of the HLA-B*58:01 allele was determined by real-time PCR-sequence-specific amplification by using the PG5801 Detection Kit (Pharmigene, Taipei). Patients with severe (SCARs) and mild (MCARs) CARs and controls were compared for differences in features prospectively collected, and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated.Results: On comparing 32 patients with SCARs and 395 tolerant controls, we identified eight strong risk factors: increased age (OR 15.1 [95% CI 5.8–40.1],P < 0.0001), female sex (OR 333 [40–43,453],P < 0.0001), allopurinol for asymptomatic hyperuricemia (OR 955 [120–125,847],P < 0.0001), allopurinol starting dose > 150 mg (OR 316 [101–122],P < 0.0001), diuretics intake (OR 304 [35–40,018],P < 0.0001), eGFR < 60 ml/min/1.73 m²(OR 100 [32–353],P < 0.0001), history of allopurinol-induced skin reaction (OR 78 [6–10,808],P = 0.004), and HLA-B*58:01 carriage (OR 147 [45–746],P < 0.0001). HLA-B*58:01 allele frequency in controls was 7.3%. For MCARs (n = 74), risk factors were eGFR < 60 ml/min/1.73 m²(OR 4.9 [1.61–14.6],P = 0.006), history of allopurinol-induced skin reaction (OR 27 [2–3777],P = 0.01), and asymptomatic hyperuricemia (OR 27 [2–3777],P = 0.01).Conclusion: This study confirmed 8 risk factors, including HLA-B*58:01, for SCARs and identified 3 risk factors for MCARs in Kinh Vietnamese. HLA-B*58:01 genotyping could guide the indication for allopurinol in Kinh Vietnamese patients with gout.

Background. HLA-B∗38:02 has been shown to be associated with antithyroid drug-induced agranulocytosis in Asian patients. Methods. HLA-B∗38:02 was analyzed by sequence-based typing in 21 patients who developed antithyroid drug-induced agranulocytosis and in 81 controls. Results. Frequency of HLA-B∗38:02 was 52.4% in agranulocytosis patients compared to 3.7% in controls (OR = 28.6, 95% CI = 6.8–120.2). Conclusions. HLA-B∗38:02 is a significant risk factor for agranulocytosis in Kinh Vietnamese patients treated with antithyroid drug.