Glutamic acid decarboxylase gene expression in thalamic reticular neurons transplanted as a cell suspension in the adult thalamus.
The goal of the present study was to determine whether alterations in neuronal morphology and connections in thalamic grafts were accompanied by changes in the expression of mRNA encoding glutamic acid decarboxylase (GAD), the key enzyme in the synthesis of GABA, the normal neurotransmitter of neurons of the thalamic reticular nucleus. Cell suspensions of rat fetal tissue containing both thalamic reticular nucleus and ventrobasal primordia were transplanted into the excitotoxically lesioned somatosensory thalamus of adult rats. Levels of messenger RNA (mRNA) encoding GAD (Mr 67,000; GAD67) were measured 7 days to 4 months following transplantation via quantitative in situ hybridization with 35S-radiolabeled antisense RNAs. Expression of GAD67 mRNA in the thalamic reticular nucleus was analyzed in parallel in rat pups between 0 and 30 days postnatally, and in adult animals. As already observed with immunohistochemistry, transplanted neurons of the thalamic reticular nucleus did not group in specific clusters but rather mingled with unlabeled (putatively ventrobasal) neurons. Levels of labelling for GAD67 mRNA per neuron increased over time and reached adult levels during the third week post-grafting, i.e. 2 weeks after the theoretical birthdate of the neurons (grafted at embryonic days 15-16). Similar values were observed and a plateau was reached at similar time points during normal ontogeny. The results suggest that, in contrast to morphology and size of the neuronal cell bodies, gene expression of GAD67 develops normally despite the ectopic location of neurons of the thalamic reticular nucleus in the somatosensory thalamus, the abnormal connectivity and the lack of segregation from non-GABAergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Nothias
F
F
INSERM CJF 91-02, Faculté de Médecine, Créteil, France.
Salin
P
P
Peschanski
M
M
Chesselet
M F
MF
D000818:Animals; D016380:Brain Tissue Transplantation / Q000473:pathology; D004790:Enzyme Induction; D016332:Fetal Tissue Transplantation; D005968:Glutamate Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000201:enzymology / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013787:Thalamic Nuclei / Q000166:cytology / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D013788:Thalamus / Q000637:transplantation*; D016042:Transplantation, Heterotopic; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D009419:Nerve Tissue Proteins; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase