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Biomedical subjects

J W Olney

Publications and source records attributed to J W Olney.

At least 163 records · Page 9Linked to original sources
PubMed1980

Brain damage in mice from voluntary ingestion of glutamate and aspartate.

Previous studies have shown that the putative excitatory neurotransmitters and neurotoxins, glutamate (Glu) and aspartate (Asp), destroy neurons in the brains of various animal species when administered orally by feeding tube. It has been argued, however that Glu and Asp are safe for human use as food additives since tube feeding is not a natural means of oral intake and efforts to demonstrate the brain damage in animals from voluntary ingestion of Glu or Asp have yielded negative results thus far. Here we demonstrate that weanling mice will voluntarily ingest large enough volumes of aqueous solutions containing Glu or Asp (or both) to sustain conspicuous hypothalamic damage. Certain deficiencies in the design of prior voluntary intake studies may explain the failure of others to demonstrate brain damage from voluntary ingestion of these excitatory neurotoxins.

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PubMed1979

Acute dendrotoxic changes in the hippocampus of kainate treated rats.

Kainic acid (KA), a potent neuroexcitatory and neurotoxic analog of glutamate (Glu), induces a widespread pattern of brain damage when administered subcutaneously to adult rats. The hippocampus is among the brain regions most consistently and severely damaged. Here we describe acute swelling of certain spines and branchlets of dendrites as the first detectable sign of KA neurotoxic changes in the hippocampus. These swellings conform to a laminar pattern suggesting selective toxic interaction of KA at specific levels of the dendritic trees of hippocampal pyramidal and dentate granule neurons. The frequency and severity of involvement of each type of hippocampal neuron at each level of its dendritic tree was roughly estimated and neuronal types were ranked from the most to least extensively involved (CA3 greater than CA4 greater than CA1 greater than CA2 greater than dentate granules). The same rank order has been described for the vulnerability of these neurons to acute destruction following intraventricular KA administration. Because the pattern of dendritic dilatations observed corresponds well with the pattern of termination of putative glutamergic inputs to the hippocampus, we interpret the findings as being consistent with the hypothesis that the toxic effects of KA are mediated through glutamergic excitatory receptors. We propose that the sensitivity of a given neuron to the neurodestructive action of KA may be determined by the percentage of its dendritic surface occupied by Glu receptors. We suspect that most, if not all, hippocampal neurons receive some glutamergic input and, therefore, are sensitive to KA. That CA3 pyramids are substantially more sensitive than dentate granules may signify that the former receive many more Glu terminals than the latter, an assumption quite consistent with our observation that focal dendritic swellings were both more densely and more widely distributed over the dendritic surfaces of the former than the latter.

Animals↗
PubMed1979

Minimal tissue concentrations of glutamate required to produce necrosis of hypothalamic neurons in newborn mice.

Groups of 4-day-old Cox Swiss albino mice were injected once subcutaneously with monosodium glutamate at several doses between 0.2 and 0.5 mg/g body weight. Glutamate, at a dose of 0.35 mg/g, produced neuronal necrosis of a very limited nature in only 60% of the animals and was defined as the minimal effective neurotoxic dose in the 4-day-old mouse. Neuronal loss was not detected in any animals treated with less than 0.35% mg/g of the amino acid whereas lesions became more extensive as the dose was increased to 0.5 mg/g. Glutamate was measured in the arcuate nucleus and plasma 0, 15, 30, 60 and 90 min after injection. These data indicated that duration of glutamate accumulation in the arcuate nucleus may be as important a variable in producing neuronal degeneration in the hypothalamus as concentration of the amino acid in that nucleus.

Animals↗
PubMed1977

Proliferation of lamellar whorls in arcuate neurons of the hypothalamus of male rats treated with estradiol benzoate or cyproterone acetate.

The arcuate nucleus of the hypothalamus (AH) of male rats which had been treated either with estradiol benzoate (E2B) or cyproterone acetate (CPA) was examined ultrastructurally for the presence of whorls of endoplasmic reticulum. The incidence of whorl containing neurons (WCN) was 2-4 times higher in the AH of animals treated for 2-3 weeks with E2B or for 2 weeks with CPA than in the AH of oil treated controls. CPA is a powerful anti-androgen while E2B acts both peripherally and centrally to limit testosterone production. These findings, together with previous evidence that whorls proliferate in AH of male rats deprived of androgen by morphine treatment or castration, suggest that steroid feedback (androgen alone or both androgen and estrogen) plays an important role in AH whorl preliferation. The possibility that WCN may be LH-RH containing neurons is suggested by the close correspondence between the number and location of WCN within AH as determined in this study and the distribution of LH-RH containing cells reported by others.

Animals↗
PubMed1976

Proliferation of lamellar whorls in arcuate neurons of the hypothalamus of castrated and morphine-treated male rats.

A comprehensive ultrastructural examination of one cross-sectional level (middle 1/3) of the arcuate nucleus of the hypothalamus (AH) of male rats several weeks after castration or after two weeks of morphine treatment confirmed a marked increased in lamellar whorls of endoplasmic reticulum in AH neurons in each group. A comparable incidence of AH whorls was not detected in rats treated with lactose, those treated for only 1--3 days with morphine, or in those given testosterone plus morphine for 2 weeks. It is postulated that the testosterone deficiency following either castration or chronic morphine treatment stimulated the observed increase in AH whorls. A close correspondence was noted between the distribution within the AH of neurons containing whorls and those reported by others to contain luteinizing hormone releasing hormone (LH-RH). The possibility that whorls may be a marker for hypothalamic neurons which play a role in the LH-RH regulatory system warrants further consideration.

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