Ischemia-induced changes in alpha-tubulin and beta-actin mRNA in the gerbil brain and effects of bifemelane hydrochloride.
Using in situ hybridization histochemistry, we examined changes in the cytoskeletal protein alpha-tubulin and beta-actin mRNAs in the gerbil brain 14 days after transient ischemia. In an attempt to identify the changes induced in the synthesis of cytoskeletal protein by ischemia, we also evaluated the effects of post-ischemia administration of bifemelane on these cytoskeletal proteins. alpha-Tubulin and beta-actin mRNAs were decreased in the CA1 region 14 days after transient ischemia. These decreases coincided with the loss of CA1 pyramidal cells, suggesting that they may have been related to delayed neuronal death. The beta-actin mRNA level in ischemic controls was significantly increased in the dentate gyrus, habenular nucleus, and medial and lateral thalamic nuclei, where some afferent nerves project into the hippocampal pyramidal cells. The increased beta-actin mRNA suggests that there may be a compensatory enhancement of actin synthesis in the afferent neurons that restores loosened synaptic connections with the ischemic cells in the CA1-4 fields. Administration of bifemelane just after recirculation prevented most of the ischemia-induced mRNA reductions in the CA1 field. Bifemelane's effect may be related to inhibition of Ca2+ influx and its radical scavenging activity. When bifemelane was administered to the ischemic group, alpha-tubulin mRNA levels significantly increased in the dentate gyrus and amygdaloid nucleus, and beta-actin mRNAs showed a tendency to increase in the CA3 and CA4 fields, dentate gyrus, and medial and lateral thalamic nuclei. These findings suggest that bifemelane may enhance synthesis of cytoskeletal protein, especially in the ischemic brain, inducing axon outgrowth or synapse formation.
Asanuma
M
M
Department of Neuroscience, Okayama University Medical School, Japan.
Ogawa
N
N
Hirata
H
H
Chou
H H
HH
Kondo
Y
Y
Mori
A
A
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism*; D005849:Gerbillinae; D006651:Histocytochemistry; D017403:In Situ Hybridization; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D013462:Sulfur Radioisotopes; D014404:Tubulin / Q000096:biosynthesis*
D000199:Actins; D000928:Antidepressive Agents; D001559:Benzhydryl Compounds; D015347:RNA Probes; D012333:RNA, Messenger; D013462:Sulfur Radioisotopes; D014404:Tubulin; C031906:bifemelane