Substrates and routes of migration of early generated neurons in the developing rat thalamus

We investigated the substrates supporting neuronal migration, and its routes, during early thalamic development in the rat. Neurons and axonal and glial fibres were identified in embryos with single and double immunohistochemistry; dynamic data were obtained with cell tracers in short-term organotypic cultured slices. The earliest thalamic neurons, originating from the ventricular neuroepithelium between embryonic days 13 and 15, include those of the reticular thalamic nucleus. At this developmental stage, calretinin, calbindin or γ-aminobutyric acid immunostaining revealed both radially and nonradially orientated neurons in the region of reticular thalamic migration, between the dorsal and ventral thalamic primordia. In cultured slices, injections of fluorescent dyes in the neuroepithelium labelled neurons in a migratory stream along radial glia in the same zone. Some labelled fusiform cells departed from this radial trajectory along orthogonal routes within the dorsal thalamus. Confocal microscopy revealed nonradially orientated neurons in close apposition with a fibre system parallel to the lateral thalamic surface. These fibres expressed axonal markers, including the intermediate filament protein α-internexin and a polysialylated form of neuronal cell adhesion molecule. Active migration of nonradially orientated neurons along neuronal substrates was confirmed in living cultured slices. In addition, in vitro and ex vivo experiments revealed neurons migrating tangentially in association with glial fibres. These results provide novel evidence that: (i) early generated thalamic neurons follow nonradial routes in addition to glia-linked radial migration; and (ii), nonradially migrating thalamic neurons move along both glial and axonal substrates, which could represent a distinctive feature of thalamic development.This work was supported by grants of the Italian Ministry of Health to C.F. and by grants PB97-0582-CO2-01 and PGC2000-2756-E of the Spanish Ministry of Science and Technology to A.F.Peer reviewe

A prospective study of the adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers.

BackgroundA diverse and abundant gut microbiome can improve cancer patients' treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT.Materials and methodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. 42 of these patients received antibiotics during the study period. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size.ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P ConclusionAfter CRT, the diversity of the gut microbiomes in this population tended to return to baseline levels by the 12 week follow-up period, but structure and composition remained significantly altered. These changes should be considered when designing studies to analyze the gut microbiome in patients who receive pelvic CRT for gynecologic cancers

Association analysis of cigarette smoking with onset of primary open-angle glaucoma and glaucoma-related biometric parameters

<p>Abstract</p> <p>Background</p> <p>To date, studies on the role played by cigarette smoking in primary open-angle glaucoma (POAG) remains controversial. The current study evaluated cigarette smoking as a risk factor of POAG and its relationships with vertical cup-to-disc ratio (VCDR), central corneal thickness (CCT) and intraocular pressure (IOP) in a Chinese cohort.</p> <p>Methods</p> <p>In a total of 248 unrelated individuals including 30 juvenile-onset POAG (JOAG), 92 adult-onset POAG (AOAG) and 126 sex-matched senile cataract controls, underwent comprehensive ophthalmic examination. Their smoking was obtained and documented by questionnaire. Association of cigarette smoking with POAG was performed using logistic regression controlled for age and sex. Effects of cigarette smoking on VCDR, IOP and CCT were analyzed with multiple linear regression.</p> <p>Results</p> <p>In either JOAG or AOAG, no association of cigarette smoking was found with disease onset (<it>P</it> = 0.692 and 0.925 respectively). In controls and JOAG, no significant effects of smoking were found on VCDR, IOP or CCT (all <it>P</it> > 0.05). Smoking was found to be correlated with decreased CCT in AOAG and combined POAG (JOAG + AOAG) (<it>P</it> = 0.009 and 0.003), but no association with VCDR or IOP was observed (<it>P</it> > 0.05).</p> <p>Conclusions</p> <p>Although cigarette smoking was not found to be risk factor for onset of POAG, it was correlated with CCT in AOAG, and thus might still play a role in the disease course, especially for AOAG.</p

A long, remarkable journey: tangential migration in the telencephalon

PMID:11715055.- ReviewRecent studies on the origin of cell populations in rodent and chicken embryonic brains provide evidence for extensive tangential migration within the developing telencephalon. On the basis of these findings, a new concept of corticogenesis has emerged, which proposes that two distinct neuronal populations cooperate in the formation of the cortex. One population consists of radially migrating neurons that originate in the ventricular zone of the pallium (cortex) and give rise to the glutamatergic pyramidal neurons. The second population consists of tangentially migrating neurons that originate in the ventricular zone of the subpallium (subcortical telencephalon) and give rise to GABA (-aminobutyric acid)-producing local circuit neurons. The subpallium is also the origin of other cell types that follow distinct tangential trajectories to migrate to structures such as the olfactory bulb and the striatum. Here, we review evidence that supports the existence of several tangential migration pathways in the telencephalon, and summarize recent findings that describe their regulation.Research in the laboratory of J.L.R.R. is supported by the Nina Ireland Laboratory, the National Institute on Drug Abuse and the National Institute of Mental Health. O.M. is the recipient of a National Alliance for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award and is a University of California, Davis, Medical Investigation of Neurodevelopmental Disorders (MIND) Institute ScholarPeer reviewe