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Biomedical subjects

J Yanai

Publications and source records attributed to J Yanai.

At least 127 records · Page 7Linked to original sources
PubMed1977

Long term reduction of male agonistic behavior in mice following early exposure to ethanol.

A system was developed to study the ability of early (pre- and neonatal) ethanol input to induce long lasting neural and behavioral changes. Ethanol was administered to E7b1/10bg and DBA/1Bg offspring through their parents who received 10% ethanol as their only liquid supply either before and during pregnancy, or from delivery until 14 days post partum, or during both periods. Thus, the offspring received ethanol transplacentally and/or through the mother's milk. The present paper is concerned with the male agonistic behavior at age 50 days of the treated offspring as compared with their pair fed controls. Early ethanol input resulted in a 23% increase in latency to attack in C57 mice and 58% in DBA, as well as a 49% (C57) and 38% (DBA) decrease in time spent fighting. The sensitive period to ethanol effect was apparently postnatal. Prenatal administration had no effect on agonistic behavior. DBA offspring were more aggressive than C57 and the scores of C57 offspring were more variable, thus indicating a lower phenotypic buffering in this strain.

Aggression↗
PubMed1976

Increased sensitivity to chronic ethanol in isolated mice.

Isolated C57BL/10 mice fed liquid diet as their only nutritional supply consumed 44% more diet than did grouped-housed mice. A similar increase due to isolation of 36% for C57BL/10 mice and 89% for DBA/1 mice was demonstrated when the sucrose in the liquid diet was replaced by an equicaloric (6% v/v) amount of ethanol. The ethanol-drinking isolated mice suffered a higher mortality rate than the grouped mice. When isolated mice were given a restricted amount of ethanol diet to match the consumption of the grouped mice, their death rate still remained higher. It was concluded that isolation increased the sensitivity to ethanol effects. The observed changes in the sensitivity to ethanol effects may have been mediated by the known isolation-induced changes in the levels of brain amines and corticosterone. Generally, DBA/1 mice were more susceptible to chronic ethanol than C57BL/10, and the young more susceptible than the adults.

Age Factors↗
PubMed1975

Effects of aminergic drugs and glutamic acid on audiogenic seizures induced by early exposure to ethanol.

Adult C57BL/10Bg mice, normally resistant to audiogenic seizures, became susceptible when the mothers drank 10 per cent ethanol in water during pregnancy and for 14 days postpartem. Reserpine enhanced the incidence of seizures, and the effect was reversed by 5-hydroxytryptophan but not by dihydroxyphenylalanine. p-Chlorophenylalanine also enhanced the incidence of seizures, whereas alpha-methyl equals p equals tyrosine did not effect. Monsodium glutamate almost completely prevented seizures. These results are consistent with the interpretation that the serotonergic systems may be among those involved in the seizure mechanism induced by fetal and early exposure to ethanol.

5-Hydroxytryptophan↗
PubMed1975

Suppressant effects of alcohol on audiogenic seizures.

Genetically seizure susceptible DBA/1/Bg mice fed 10% ethanol in their drinking water exhibited a marked diurnal variation in blood alcohol levels. At peak levels, sound-induced seizures were significantly reduced. At trough levels, seizures remained unaffected. Ethanol administered during early development enhanced seizures at post-weaning age. Such alcohol-augmented seizures were suppressed by ethanol feeding during the testing period, to the same base level as in animals not pretreated with ethanol in early life.

Acoustic Stimulation↗
PubMedDate not supplied

Alterations in hippocampal cholinergic receptors and hippocampal behaviors after early exposure to nicotine.

Mice were exposed to nicotine prenatally by injecting the mother with 1.5 mg/kg nicotine SC twice daily on gestation days 9-18 (PreN mice) or neonatally by daily SC injections of 1.5 mg/kg nicotine on postnatal days 2-21 (NeoN mice). At age 50 days, hippocampal muscarinic receptors Bmax of PreN and NeoN mice were 58% and 79% above control, respectively (p less than 0.01); Kd was unaffected by early nicotine exposure. Eight-arm maze performance of nicotine-exposed animals fell behind control level. Both PreN and NeoN made approximately 10% less correct responses in the first eight trials than controls throughout the test period (p less than 0.01). By the last day of testing, PreN needed 23% and NeoN 31% more trials than controls to enter all arms (p less than 0.001). In addition, PreN needed 35 and NeoN 42% more days than controls to reach criterion (p less than 0.05). Similarly, while 61% of controls reached criterion by day 6 only 17% of PreN and 25% of NeoN reached criterion (p less than 0.01). In the Morris maze, PreN needed from 43-119% more time to reach the platform (p less than 0.001). In the spatial probe test, PreN animals made 35% fewer crosses over the area of the missing platform (p less than 0.001). The study suggests that nicotine administered to the fetus or neonate alters septohippocampal chemistry and induces deficits in hippocampus-related behaviors. The possible reversal of the behavioral changes by manipulating the cholinergic innervations should be the subject of future investigations.

Animals↗
PubMedDate not supplied

Altered brain sensitivity to ethanol in mice after MPTP treatment.

Previous studies demonstrated the role of the dopaminergic receptors in brain sensitivity to ethanol. The present study was designed to assess the relative contribution of the nigrostriatal component to this brain sensitivity. Adult male C57BL mice were given 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) injections (30 mg/kg daily for 2 consecutive days). The treatment decreased the striatal dopamine level by 35% from the control level, and the number (Bmax) of dopaminergic receptors was increased by 67%. Ethanol-induced sleep time was reduced in the MPTP-treated mice, as compared to controls, and this gap progressively widened during the 3 weeks of testing to 29%. Brain ethanol levels upon awakening increased by 22%. The results suggest that the nigrostriatal dopaminergic pathways play a major role in determining brain sensitivity to ethanol which may represent an important component in the addictive process.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMedDate not supplied

Neuromorphological changes in mouse olfactory bulb after neonatal exposure to phenobarbital.

Heterogeneous Sabra mice pups were injected daily with 50 mg/kg phenobarbital (B50) or 40 mg/kg (B40) from postnatal day 2 (P2) to P21. Control litter mates (C) received vehicle injections. All animals were killed on P50 and their brains removed for histological analysis. The volumetric growth of the main olfactory bulb (MOB) was assessed in hematoxylin and eosin-stained serial sections cut in the sagittal plane. The volume of MOB was reduced 20 to 25% in barbiturate-treated mice. The greatest reductions in volume were seen in the external layers of the bulb (20 to 28%). There were moderate reductions in the internal granular layer (IGL, 6 to 20%) and no reductions in the subependymal layer that contains the migrating and immature cells. The number of prenatally-formed mitral cell neurons was unaffected by the treatment while the number of the pre- and postnatally generated granule cells was significantly reduced in the B40 group. There were no treatment effects on the sizes or packing densities of the mitral or granule cells. Like the hippocampus and the cerebellum, the developing MOB is vulnerable to barbiturate-exposure.

Animals↗
PubMedDate not supplied

Deficits in development of central cholinergic pathways caused by fetal nicotine exposure: differential effects on choline acetyltransferase activity and [3H]hemicholinium-3 binding.

Nicotine has been hypothesized to induce neurobehavioral teratology by mimicking prematurely the natural developmental signals ordinarily communicated by the ontogeny of cholinergic synaptic transmission. In the current study, the effects of fetal nicotine exposure (2 mg/kg/day or 6 mg/kg/day) on development of central cholinergic pathways were examined in striatum and hippocampus of animals exposed from gestational days 4 through 20, using maternal infusions with osmotic minipumps. Brain region weights and choline acetyltransferase activity, an enzymatic marker for development of cholinergic nerve terminals, were within normal limits in the nicotine-exposed animals. However, development of [3H]hemicholinium-3 binding which labels the presynaptic high affinity cholinergic transporter, was deficient in both striatum and hippocampus. Abnormalities occurred during two distinct phases; in the early neonatal period, when [3H]hemicholinium-3 binding sites are transiently overexpressed, and during or after the period of rapid synaptogenesis, when binding in controls is rising consequent to the increase in nerve impulse activity. These data thus indicate that fetal nicotine exposure, even at doses that do not cause overt signs of maternal/fetal/neonatal toxicity or growth impairment, influences both specific gene expression of cholinergic nerve terminal markers, as well as indices of neuronal function. Comparison of regional selectivity at the two dose levels indicated greater sensitivity of the striatum, a region with a prenatal peak of neuronal mitosis, as compared to hippocampus, where mitosis peaks postnatally; the regional differences are consistent with vulnerability to nicotine during a critical phase of cell development.

Acetylcholine↗
PubMedDate not supplied

Fetal nicotine exposure alters ontogeny of M1-receptors and their link to G-proteins.

Prenatal nicotine exposure has been shown to disrupt the development of cholinergic presynaptic tone and behaviors mediated through muscarinic cholinergic receptors. The current study examines nicotine's effects on ontogeny of postsynaptic muscarinic M1-receptors in rat striatum and hippocampus after continuous maternal infusions of 2 mg/kg/day or 6 mg/kg/day from gestational days 4 through 20. Although brain region weights were unaffected by nicotine exposure, significant alterations in receptor development and receptor regulation by G-proteins were found. Postnatal development of striatal M1-receptor binding, as identified with [3H]pirenzepine, was significantly impaired with either of the fetal nicotine regimens. Treatment with 2 mg/kg/day also produced alterations in striatal receptor affinity state, characterized by enhanced ability of an agonist (oxotremorine-M) to displace [3H]pirenzepine; raising the dose to 6 mg/kg/day masked the affinity shift by affecting G-protein regulatory mechanisms, such that addition of the GTP analog, GppNHp, produced a larger decrease in agonist affinity. In the hippocampus, no such effects on receptor binding, affinity state, or G-protein regulation were seen with either regimen. These data thus indicate that fetal nicotine exposure, even at doses that do not cause overt signs of maternal/fetal/neonatal toxicity or growth impairment, influences cholinergic receptor development and regulation of cell signaling mediated by G-proteins. The selectivity of effects toward M1-receptors in the striatum, a region with a prenatal peak of neuronal mitosis, as compared to hippocampus, where mitosis peaks postnatally, suggests that vulnerability to nicotine involves a critical phase of cell development, rather than being targeted toward receptors of a given subtype.

Animals↗