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PubMed1976

Effect of stagnant hypoxia on acid ribonuclease activity in the rat prosencephalon during ontogenesis.

In the rat prosencephalon it proved possible to differentiate lysosomal ribonuclease from alkaline ribonuclease activity, which could be detected only in the presence of p-chlormercuribenzoate. Acid RNase activity related to the amount of protein in the prosencephalon fell during ontogenesis. It was not significantly affected by four hours' stagnant hypoxia induced by ligation of both carotids. Its release from the lysosomes rose, however (when isotonic homogenates were spun at 20,000 g, acid ribonuclease activity in the supernatants was elevated). The absence of correlation between this activation and the degree of maturity of the nervous tissue refutes the hypothesis that regulation of this enzyme is per se responsible for the known changes induced by hypoxia in the RNA content of the prosencephalon of rats of different ages. On the contrary, the results indirectly support studies which demonstrate changes in the extent of RNA synthesis after hypoxia.

Age Factors↗
PubMed1979

Cephalic neurulation and optic vesicle formation in the early mouse embryo.

The overall pattern of cephalic neurulation and the concomitant early development of the optic vesicles in mouse embryos were examined by scanning electron microscopy. Paraffin-sectioned specimens were also examined. The overall pattern of closure of the cephalic neural folds accords well with earlier observations of this process. The earliest indication of optic placode formation was seen in histological sections of embryos at the 4-somite stage, while optic pit formation was first observed at the 5- to 6-somite stage. The upper halves of the optic vesicles were formed in 10- to 15-somite embryos by the fusion of the neural folds at the junction between the mesencephalon and prosencephalon, while closure of the lower halves was associated with the closure of the rostral neuropore, and was usually completed by about the 20-somite stage. By the 25- to 30-somite stage, a rapid increase in the volume of the forebrain was observed, so that the optic vesicles were displaced laterally. An overall increase in the volume of the optic vesicles and decrease in the diameter of the optic stalks were also observed at this time. This account of cephalic neurulation and optic organogenesis provides useful baseline data relevant to the study of the normal early development of the mouse. A comparison is made between similar events in the rat, the hamster, and the human embryo.

Animals↗
PubMed1976

Effect of long-term hypoxia upon the activity of some enzymes in the brain of rats during early postnatal ontogenesis and in adulthood.

Enzymatic activities were determined in the prosencephalon of rats which had been exposed repeatedly for 8 hrs, either from the age of 1 to 17 days or in adulthood, to an altitude of 7,000 m in a barometric chamber (up to a total of 104 hrs). The activity of enzymes was assayed 20 hrs after the last exposure. The results were compared with values obtained 20 hrs after a single 8-hour exposure to a stimulated altitude of 7,000 m in 17-day-old and adult rats. In young rats a single exposure to hypoxia, the most elevated was the activity of LDH and isoCDH, while GPT and CPK were decreased. After repeated hypoxia, the most significant increasw was noted in the activity of PK and again a decrease in GPT and CPK. In adulthood, a single exposure to hypoxia causes the greatest increase in CPK, while LDH and GOT are reduced. Following repeated hypoxia, none of the enzyme activities were increased by more than 20%, while LDH, GOT, GIDH and CPK were again lower. It is concluded from these results that a single exposure to hypoxia increases anaerobic glycolysis in the immature nervous tissue and improves its oxygen utilization. The relationship between glycid and amino acid metabolism are not appreciably altered. On the other hand, a general reduction of bioenergetics and biosynthesis occurs in adulthood. Repeated hypoxia, on the contrary, has similar after-effects in both age groups, namely inhibition of aerobic metabolism and of the relations between glycid and amino acid metabolism.

Age Factors↗
PubMed2026

Ank3 loss in adult forebrain excitatory neurons disrupts behavior, neuronal activity, membrane proteome, and myelination.

ANK3, encoding the scaffolding protein ankyrin-G, is a major risk gene for bipolar disorder and schizophrenia, but its cellular and circuit-level mechanisms remain poorly defined. Here, we demonstrate that deletion of Ank3 in forebrain excitatory neurons-either prenatally (Ank3-/-:Emx1-Cre) or in adolescence (Ank3-/-:CaMKIIα-Cre) leads to convergent behavioral phenotypes in adulthood, including hyperactivity, reduced anxiety-like behavior, and decreased depression-like responses. Calcium imaging in cultured neurons and acute brain slices revealed that ankyrin-G loss reduces both spontaneous and evoked neuronal activity. Quantitative proteomic profiling of membrane-enriched cortical fractions uncovered widespread remodeling of the synaptic proteome, including upregulation of the kinase Taok2 and unexpected downregulation of myelin basic protein (Mbp), a structural component of oligodendrocyte-derived myelin. Importantly, chronic lithium treatment, known to reverse behavioral abnormalities in Ank3-deficient mice, also restored Mbp expression. Together, our findings identify ankyrin-G as a molecular bridge between excitatory neuronal activity, synaptic structure, and myelin-associated protein expression, revealing a pathway by which ANK3 variants may contribute to neuropsychiatric disease.

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