James H. Baker

The brain response to 2-deoxy glucose is blocked by a glial drug

Two brain regions - the basomedial hypothalamus and area postrema (AP) - react to changes in circulating glucose levels by altering feeding behavior and the secretion of pituitary and non-pituitary hormones. The precise identity of cells responding to glucose in these regions is uncertain. The recent detection of high-capacity glucose transporter proteins in astrocytes in these areas has suggested that astrocytes may play a role in glucose sensing by the brain. To test this hypothesis, rats were injected with either saline or methionine sulfoximine (MS), a compound that produces alterations in carbohydrate and glutamate metabolism in astrocytes. Eighteen hours later, rats were injected with either saline or 2-deoxy glucose (2-DG) and brain sections were stained to demonstrate 2-DG-activated neurons immunoreactive for Fos protein. MS-treated rats showed a 70% reduction in numbers of Fos+ neurons in the AP region (p<0.05). Also, specialized, Gomori+ astrocytes were particularly abundant in both glucose sensitive regions and showed a distribution identical to that reported for high-capacity glucose transporter proteins. These data suggest that specialized astrocytes influence the glucose-sensing function of the brain.

Immunoreactivity for brain‐fatty acid binding protein in gomori‐positive astrocytes

Gomori‐positive (GP) astrocytes are a subset of brain astrocytes with highly stained cytoplasmic granules that arise from the degradation of mitochondria. The GP granules of these astrocytes are most prominent in the arcuate nucleus of the hypothalamus, but can also be detected in the olfactory bulbs, hippocampus, habenula, and other selected brain regions. The cause and functional effects of this mitochondrial pathology in these glia are not yet known with certainty.

EVIDENCE FOR POLAR CYTOPLASM/NUAGE IN RAT OOCYTES

 In many organisms oocytes contain dark-staining material, termed nuage, that is concentrated at one pole of the oocyte cytoplasm and that influences the further development of the oocyte after fertilization. In mammalian oocytes, ultrastructural studies have detected small patches of nuage-like material, but thus far no nuage-rich zone of polar cytoplasm has been reported. Here, we report that when large sections of rat ovary embedded in methacrylate resin are stained with toluidine blue and surveyed, many oocytes contain a narrow, sharply defined, basophilic zone of polar cytoplasm that appears analogous to the polar cytoplasm of Xenopus and other non-mammalian species. This basophilic polar cytoplasm was common in multilaminar follicles and was not visible in smaller, primordial follicles. In one out of five oocytes stimulated with hCG to complete the first meiotic division, a relatively faint region of cortical basophilia was detectable. Further studies will be needed to ascertain if this nuage-like material has an influence upon the development of oocytes similar to that seen in non-mammalian species.

A PROGRESSIVE BALLOONING OF MYELINATED, TH-POSITIVE AXONS IS PRODUCED BY MPTP IN THE DOG

Systemic injections of l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) produce selective degeneration of the dopaminergic neurons of the nigrostriatal pathway in some mammals such as dogs, monkeys, and humans but not others such as rats. The mechanism of MPTP’s actions has been studied by biochemical and pharmacological techniques which have found that MPTP’s toxicity requires its oxidation by glial MAO-B to l-methyl-4-phenylpyridinium (MPP+)1–3. Surprisingly, MPP+ is not selectively toxic to dopaminergic neurons but damages or kills most cells with which it comes into contact including hepatocytes and granule cells of the cerebellum4,5.