S-ketamine administration in pregnant mice induces ADHD- and depression-like behaviors in offspring mice.

BACKGROUND: Anesthesia and psychotropic drugs in pregnant women may cause long-term effects on the brain development of unborn babies. The authors set out to investigate the neurotoxicity of S-ketamine, which possesses anesthetic and antidepressant effects and may cause attention deficit hyperactivity disorder (ADHD)- and depression-like behaviors in offspring mice. METHODS: Pregnant mice were administered with low-, medium-, and high-dose S-ketamine (15, 30, and 60 mg/kg) by intraperitoneal injection for 5 days from gestational day 14-18. At 21 days after birth, an elevated plus-maze test, fear conditioning, open field test, and forced swimming test were used to assess ADHD- and depression-like behaviors. Neuronal amount, glial activation, synaptic function indicated by ki67, and inhibitory presynaptic proteins revealed by GAD2 in the hippocampus, amygdala, habenula nucleus, and lateral hypothalamus (LHA) were determined by immunofluorescence assay. RESULTS: All the pregnant mice exposed to high-dose S-ketamine administration had miscarriage after the first injection. Both low-dose and medium-dose S-ketamine administration significantly increased the open-arm time and attenuated frozen time in the fear conditioning, which indicates impulsivity and memory dysfunction-like behaviors. Medium-dose S-ketamine administration reduced locomotor activity in the open field and increased immobility time in the forced swimming test, indicating depression-like behaviors. Changes in astrocytic activation, synaptic dysfunction, and decreased inhibitory presynaptic proteins were found in the hippocampus, amygdala, and habenula nucleus. CONCLUSIONS: These results demonstrate that S-ketamine may lead to detrimental effects, including ADHD-and depression-like behaviors in offspring mice. More studies should be promoted to determine the neurotoxicity of S-ketamine in the developing brain.

[Mechanism studies on the combination reaction between bovine serum albumin and zincon by fluorescence spectra].

The characteristics of binding reaction between bovine serum albumin (BSA) and zincon (ZCN) were studied by fluorescence spectra and ultraviolet-visible absorption spectra. The bovine serum albumin can emit fluorescence (lamda(em) = 345 nm) under irradiation of ultraviolet light (lamda(ex) = 280 nm). After the zincon (ZCN) was added into BSA solution the fluorescence of BSA was quenched partially. The results indicated that ZCN was strongly bound to BSA. According to Stern-Volmer equation and Lineweaver-Burk equation, the quenching constant and the thermodynamic parameters were obtained. From the thermodynamic parameters the binding power between ZCN and BSA can be judged. The binding distance (r = 5.07 nm) and energy transfer efficiency (E = 0.67) between donor (BSA) and acceptor (ZCN) were obtained by Forster's non-radiative energy transfer mechanism. It is confirmed that the combination reaction between ZCN and BSA is a single static quenching process, and their interaction may be interpreted with energy transfer mechanism.

[Studies on the thermodynamics and mechanism of combination reaction of titan yellow with bovine serum albumin].

The characteristics of the binding reaction of titan yellow(TY) with bovine serum albumin(BSA) were studies by fluorescence and ultraviolet-visible absorption spectra. It was shown that TY has a powerful ability to quench the fluorescence intensity of BSA. The fluorescence quenching data were analyzed according to Stern-Volmer equation and Line weaver-Burk equation and the binding constant, and thermodynamic parameters were obtained. According to the thermodynamic parameters the main sorts of binding force were determined. The binding distance and energy transfer efficiency between the donor (BSA) and the acceptor (TY) were obtained by Förster's non-radiative energy transfer mechanism. It is confirmed that the combination reaction of TY with BSA is a single static quenching process, and their interaction may be interpreted with energy transfer mechanism.

[The up-regulation of p-p38 MAPK during the induction of brain ischemic tolerance induced by intermittent hypobaric hypoxia preconditioning in rats].

OBJECTIVE: To explore the expression of p-p38 MAPK protein and the number of astrocytes expressing p-p38 MAPK in CA1 hippocampus in rats during the induction of brain ischemic tolerance induced by intermittent hypobaric hypoxia (IH) preconditioning. METHODS: Thirty healthy adult male Wistar rats were randomly divided into 6 groups (n = 5 in each group): sham 0 min group, IH + sham 0 min group, sham 7 d group, IH + sham 7 d group, Ischemia (Is) 7 d group, and IH + Is 7 d group. Neuropathological evaluation was performed by thionine staining in CA1 hippocampus in rats. The expression of p-p38 MAPK in CA1 hippocampus was observed by immunohistochemical staining. And the number of astrocytes expressing p-p38 MAPK was observed by immunofluorescent double labeling. RESULTS: The results showed that IH preconditioning induced brain ischemic tolerance successfully. At the same time, IH preconditioning obviously up-regulated the expression of p-p38 MAPK protein in CA1 hippocampus, and also increased the number of astrocytes expressing p-p38 MAPK. CONCLUSION: It might be concluded that IH preconditioning induced brain ischemic tolerance by up-regulating the expression of p-p38 MAPK protein in pyramidal neurones and astrocytes.