Interleukin(IL)-2 supported the survival and enhanced neurite extension of cultured hippocampal neurons prepared from embryonic 18-day-old rats. This neurotrophic effect was observed at concentrations of 2 to 200 U/ml, and almost all the neurons could survive for more than 2 days in the presence of 200 U/ml of IL-2. This viability-promoting effect of IL-2 on the neurons was completely blocked with anti-IL-2 antibodies. IL-2 also supported the survival of cultured cortical, striatal, and septal neurons. These results indicate that IL-2 has a survival-promoting effect on a wide variety of neurons. On the other hand, IL-2 did not affect the choline acetyltransferase (ChAT) activity of striatal neurons, suggesting that this cytokine does not act as a differentiation factor for striatal cholinergic neurons.

To examine the regulation of nerve growth factor (NGF) gene expression with respect to neural trauma, we examined the effects of T cell-derived lymphokines on NGF synthesis/secretion in cultured mouse astrocytes. Interleukin (IL)-4 and IL-5 significantly increased the amount of NGF secreted by astrocytes, whereas IL-2, IL-3, and IL-6 had no significant effect. IL-4 and IL-5 produced marked increases in NGF mRNA levels in astrocytes as demonstrated by the reverse transcription-polymerase chain reaction (RT-PCR) method. The effect of IL-4 and IL-5 was greater in quiescent astrocytes than in growing cells. Neither increase in thymidine incorporation nor any morphological change was observed during the treatment with IL-4 and IL-5. The stimulatory effect of IL-4 and IL-5 on NGF synthesis was completely inhibited by the addition of anti-IL-4 monoclonal antibody and anti-IL-5 monoclonal antibody, respectively. The results indicate that IL-4 and IL-5 specifically trigger a cascade of events to regulate NGF synthesis in astrocytes, independent of cell growth.

The effects of thalidomide on the embryofetal development (EFD) of rabbit fetuses and the sensitive periods (SP) for the various malformations were compared between Kbl:JW and Kbl:NZW rabbits to investigate possible strain differences. The post-implantation loss rate and number of placental remnants were increased and the number of live fetuses was decreased in both of the strains in the EFD study and in Kbl:NZW at 300 mg/kg dosed on GD 7-8 in the SP study. In the external and skeletal examinations, head, limb and tail malformations were observed in both the strains in the EFD and SP studies at the same dose levels in the same dosing period. In the visceral examination, hydrocephaly, cardiovascular malformations, absent pulmonary intermedial lobe, diaphragmatic hernia and/or abnormal liver lobation were also observed in both of the strains in the EFD and SP studies at the same dose levels and in the same dosing period. Plasma concentrations of thalidomide were equivalent between the two strains in the SP study. There were strain differences in some parameters, such as the post-implantation loss rate and the frequencies of malformations in forelimb and hindlimb and pulmonary intermedial lobe, but similar types of malformations or variations were induced at the same dose levels on the same dosing period in both strains. Therefore, it is concluded that there were no essential differences in sensitivity of the fetuses to thalidomide between Kbl:JW and NZW rabbits and both of the strains are useful to evaluate the teratogenic effects of thalidomide.

Interferon (IFN)‐β and IFN‐γ inhibited the DNA synthesis and nerve growth factor (NGF) synthesis in growing astrocytes cultured from neonatal mouse brain, but they did not affect the NGF synthesis in quiescent astrocytes. IFN‐β and IFN‐γ also inhibited the enhanced DNA synthesis and NGF synthesis in growing astrocytes after the administration of basic fibroblast growth factor. These results indicated that NGF synthesis in astrocytes is regulated by IFNs associated with cell growth. The mechanism of IFN action on NGF synthesis/secretion is unknown, but the results that their effects last long after IFN removal from the cultures present the possibility that IFNs destabilize NGF mRNA.

Atrazine, a commonly used herbicide, suppresses the luteinizing hormone (LH) surge in female rats, although the underlying mechanism remains unclear. Kisspeptin, encoded by the Kiss1 gene, is a hypothalamic peptide that controls gonadotropin-releasing hormone (GnRH) release from the GnRH neurons. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) are involved in regulating pre-ovulatory GnRH and LH surge. To clarify the effect of atrazine on the LH surge in female rats, we investigated its effects on hypothalamic GnRH and kisspeptin. Ovariectomized female rats in a high-dose estradiol supplementation model were orally administered vehicle or 100 mg/kg of atrazine once daily for 5 days. This attenuated the LH surge but did not affect baseline LH levels, with no difference in hypothalamic GnRH levels between the vehicle-treated and atrazine-treated animals. After the fifth treatment, subcutaneous administration of kisspeptin (at 0, 0.1, 1, and 10 nmol/kg) induced a dose-dependent LH release almost equivalent in the vehicle- and atrazine-treated animals, suggesting that GnRH neurons maintain normal responsiveness to kisspeptin. However, Kiss1 mRNA expression levels in the AVPV were significantly reduced in the atrazine-treated animals. Given the normal response of GnRH neurons to exogenously administered kisspeptin, the suppressive effect of atrazine may be explained by suppression of Kiss1 expression in the AVPV leading to the attenuation of kisspeptin release from kisspeptin neurons in the AVPV. Further studies are warranted to elucidate more precisely the mechanism of atrazine's involvement in the suppression of Kiss1 mRNA expression in the AVPV.