Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, gamma-aminobutyric acid (GABA)-expressing cells migrate in vitro from the subcortical telencephalon into the neocortex. The number of GABA-expressing cells in neocortical slices is reduced by separating the neocortex from the subcortical telencephalon. Finally, mice lacking the homeodomain proteins DLX-1 and DLX-2 show no detectable cell migration from the subcortical telencephalon to the neocortex and also have few GABA-expressing cells in the neocortex.

During corticogenesis, early-born neurons of the preplate and layer 6 are important for guiding subsequent neuronal migrations and axonal projections. Tbr1 is a putative transcription factor that is highly expressed in glutamatergic early-born cortical neurons. In Tbr1-deficient mice, these early-born neurons had molecular and functional defects. Cajal-Retzius cells expressed decreased levels of Reelin, resulting in a reeler-like cortical migration disorder. Impaired subplate differentiation was associated with ectopic projection of thalamocortical fibers into the basal telencephalon. Layer 6 defects contributed to errors in the thalamocortical, corticothalamic, and callosal projections. These results show that Tbr1 is a common genetic determinant for the differentiation of early-born glutamatergic neocortical neurons and provide insights into the functions of these neurons as regulators of cortical development.

Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.

A common pathological finding in autism is a localized deficit in Purkinje cells (PCs). Cerebellar abnormalities have also been reported in schizophrenia. Using a mouse model that exploits a known risk factor for these disorders, maternal infection, we asked if the offspring of pregnant mice given a mid-gestation respiratory infection have cerebellar pathology resembling that seen in these disorders. We also tested the effects of maternal immune activation in the absence of virus by injection of the synthetic dsRNA, poly(I:C). We infected pregnant mice with influenza on embryonic day 9.5 (E9.5), or injected poly(I:C) i.p. on E12.5, and assessed the linear density of PCs in the cerebellum of adult or postnatal day 11 (P11) offspring. To study granule cell migration, we also injected BrdU on P11. Adult offspring of influenza- or poly(I:C)-exposed mice display a localized deficit in PCs in lobule VII of the cerebellum, as do P11 offspring. Coincident with this are heterotopic PCs, as well as delayed migration of granule cells in lobules VI and VII. The cerebellar pathology observed in the offspring of influenza- or poly(I:C)-exposed mice is strikingly similar to that observed in autism. The poly(I:C) findings indicate that deficits are likely caused by the activation of the maternal immune system. Finally, our data suggest that cerebellar abnormalities occur during embryonic development, and may be an early deficit in autism and schizophrenia.

Epidemiological studies have shown that maternal infection can increase the risk for mental illness in the offspring. In a mouse model of maternal respiratory infection with influenza virus, the adult offspring display striking behavioral, pharmacological and histological abnormalities. Although influenza primarily infects the respiratory system, there are reports of viral mRNA and protein in the fetus of infected pregnant animals. To determine the extent of viral spread following maternal respiratory infection, we used RT-PCR to assay various maternal and fetal tissues for influenza A mRNAs coding for neuraminidase, non-structural protein 2, nuclear protein and matrix protein. While infected maternal lungs exhibit uniformly very strong signals, placentae are only rarely positive, and viral RNAs are not detectable in fetal brains from infected mothers. Thus, the effects of maternal infection on fetal brain development are likely to be indirect, probably involving the maternal inflammatory response.

Herein, the genetic control of regionalization and connectivity of the neocortex are reviewed. Evidence is accumulating which suggests that intrinsic mechanisms have a central role in controlling cortical regional specification and differentiation. Expression patterns of several genes (Id-2, Tbr-1, cadherin-6, cadherin-8, neuropilin-2, Wnt-7b, Eph-A7 and RZR-beta) are described; the expressions of these genes have regional boundaries which demarcate distinct functional areas of the cerebral cortex in neonatal mice.

Octacosanol has multiple biological functions. In this study, the anti-inflammatory effect and molecular mechanism of octacosanol were evaluated by using dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice and lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells. The colitis mouse model was induced by 3.0% DSS in 8-week ICR mice and octacosanol orally administered with 100 mg/kg/day. The results showed that octacosanol significantly improved the health status of mice and reduced DSS-induced pathological damage in the colonic tissues. Octacosanol obviously inhibited the mRNA and protein expression levels of pro-inflammatory factors of colonic tissues. In vitro, octacosanol administration significantly reduced the expression of mRNA or protein of pro-inflammatory cytokines and the phosphorylation of c-Jun N-terminal kinase and p38, and it also partly prevented LPS-induced translocations of NF-κB and AP-1. Octacosanol has anti-inflammatory effect, and its molecular mechanism may be involved in downregulating the expression of inflammatory factors and blocking of MAPK/NF-κB/AP-1 signaling pathway.

Ulcerative colitis is a major inflammatory bowel disease (IBD), characterized by inflammation within the gastrointestinal tract through chronic or relapsing immune system activation. The aim of this study is to investigate the potential protective effect of oat β-glucan (βG) against colitis induced by DSS in mice. Eighty mice were randomly divided into the control group (no DSS, no βG), DSS group (DSS only), DSS + L-βG group (DSS plus 500 mg per kg βG), and DSS + H-βG group (DSS plus 1000 mg per kg βG). Compared with the DSS group, administration of βG significantly reduced clinical symptoms with less weight loss, diarrhea and shortening of the colon, the severity of colitis was significantly inhibited as evidenced by the reduced disease activity index (DAI) and degree of histological damage in colon. Moreover, treatment with βG not only decreased myeloperoxidase activity (MPO), and nitric oxide (NO) and malondialdehyde (MDA) levels, but also inhibited mRNA and protein expression of pro-inflammatory factors such as TNF-α, IL-1β, IL-6 and iNOS. This suggests that oat βG in diet might exhibit an anti-inflammatory function against colitis through inhibition of expression of pro-inflammatory factors.