Thyroid control over biomembranes: VI. Lipids in liver mitochondria and microsomes of hypothyroid rats

The lipids of liver mitochondria prepared from normal rats and from rats made hypothyroid by thyroidectomy and injection with131INa contained similar amounts, per mg protein, of total lipids, phospholipids, neutral lipids and lipid phosphorus. Hypothyroidism caused a doubling of the relative amounts of mitochondrial cardiolipins (CL; to 20.5% of the phospholipid P) and an accompanying trend (although statistically not significant) toward decreased amounts of both phosphatidylcholines (PC) and phosphatidylserines (PS), with phosphatidylethanolamines (PE) remaining unchanged. The pattern of elevated 18∶2 fatty acyl content and depleted 20∶4 acyl groups of the mitochondrial phospholipids of hypothyroid preparations was reflected to varying degrees in the resolved phospholipids, with PC showing greater degrees of abnormality than PE, and CL showing none. Hypothyroidism produced the same abnormal pattern of fatty acyl distributions in liver microsomal total lipids as was found in the mitochondria. Hypothyroid rats, when killed 6 hr after injection of [1‐14C] labeled linoleate, showed the following abnormalities: the liver incorporated less label into lipids, and converted 18∶2 not exclusively to 20∶4 (as normals do) but instead incorporated the label mainly into saturated fatty acids. These data, together with the known decrease in β‐oxidation, suggest that hypothyroidism involves possible defective step(s) in the conversion of 18∶2 to 20∶4.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142296/1/lipd0328.pd

Differential Hippocampal Protection when Blocking Intracellular Sodium and Calcium Entry during Traumatic Brain Injury in Rats

This study investigated the contributions of the reverse mode of the sodium-calcium exchanger (NCX) and the type 1 sodium-proton antiporter (NHE-1) to acute astrocyte and neuronal pathology in the hippocampus following fluid percussion traumatic brain injury (TBI) in the rat. KB-R7943, EIPA, or amiloride, which respectively inhibit NCX, NHE-1, or NCX, NHE-1, and ASIC1a (acid-sensing ion channel type 1a), was infused intraventricularly over a 60-min period immediately prior to TBI. Astrocytes were immunostained for glial fibrillary acidic protein (GFAP), and degenerating neurons were identified by Fluoro-Jade staining at 24 h after injury. Stereological analysis of the CA2/3 sub-regions of the hippocampus demonstrated that higher doses of KB-R7943 (2 and 20 nmoles) significantly reduced astrocyte GFAP immunoreactivity compared to vehicle-treated animals. EIPA (2–200 nmoles) did not alter astrocyte GFAP immunoreactivity. Amiloride (100 nmoles) significantly attenuated the TBI-induced acute reduction in astrocyte GFAP immunoreactivity. Of the three compounds examined, only amiloride (100 nmoles) reduced hippocampal neuronal degeneration assessed with Fluoro-Jade. The results provide additional evidence of acute astrocyte pathology in the hippocampus following TBI, while suggesting that activation of NHE-1 and the reverse mode of NCX contribute to both astrocyte and neuronal pathology following experimental TBI

Association between cell swelling and glycogen content in cultured astrocytes

Treatment of cultured rat astrocytes with hypotonic media or with 1 mM glutamate for 90 min caused cell swelling and a significant increase in glycogen content. Conversely, treatment with hypertonic media caused cell shrinkage with a corresponding decrease in astrocyte glycogen, which was proportional to the increasing osmolality of the hypertonic media. The glutamate receptor antagonist, MK‐801, lowered both the glutamate‐induced swelling and glycogen increase. These findings demonstrate a correlation between changes in cell volume and astrocyte glycogen content. This may explain the increased astrocytic glycogen observed in many neuropathological conditions where astrocyte swelling occurs. Because glycogen represents the largest energy reserve in the central nervous system, a swelling‐induced disturbance in glycogen metabolism may lead to abnormal glial‐neuronal interactions resulting in impaired brain bioenergetics