The glutaminergic, GABAergic, dopaminergic but not cholinergic neurons are susceptible to anaesthesia-induced cell death in the rat developing brain.
Neuronal cell death induced by anaesthetics in the developing brain was evident in previous pre-clinical studies. However, the neuronal cell types involved in anaesthesia-induced neuronal cell death remains elusive. The aim of this study was to investigate glutamatergic, GABAergic, cholinergic and dopaminergic neuronal cell apoptosis induced by anaesthetic exposure in specific brain regions in rats. Separate cohorts of 7-day-old Sprague Dawley (SD) rat pups were randomly assigned to two groups: Naive and anaesthetics alone (70% nitrous oxide and 0.75% isoflurane exposure for 6 h). The brains were sectioned and the slices that contained the basal forebrain, substantia nigra, cornu ammonis area 1 (CA1) subarea of hippocampus or cingulate cortex were selected and subsequently subjected to double-labelled fluorescent immunohistochemistry for choline acetyltransferase, dopamine, vesicular glutamate transporter 1 (vGLUT1) or glutamic acid decarboxylase 67 (GAD67) together with caspase 3, respectively. Compared to the naive control, anaesthetic exposure significantly increased the number of caspase-3 positive cells in the CA1 subarea of hippocampus, cingulate cortex, and substantia nigra, but not in the basal forebrain. 54% and 14% of apoptotic cells in the CA1 subarea of hippocampus were GABAergic and glutamatergic neurons respectively. In the cingulate cortex, 30% and 37% of apoptotic cells were GABAergic and glutamatergic neurons respectively. In the substantia nigra, 22% of apoptotic cells were dopaminergic neurons. Our data suggests, anaesthetic exposure significantly increases neuroapoptosis of glutamatergic, GABAergic and dopaminergic neurons in the developing brain but not that of the cholinergic neurons in the basal forebrain.
Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London SW10 9NH, UK.
Z-W
ZW
Zhou
Y
Y
Shu
M
M
Li
X
X
Guo
C
C
Pac-Soo
M
M
Maze
D
D
Ma
D000109:Acetylcholine / Q000378:metabolism*; D000758:Anesthesia / Q000009:adverse effects*; D019162:Anesthetics, Combined / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D053148:Caspase 3 / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D007530:Isoflurane / Q000009:adverse effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009609:Nitrous Oxide / Q000009:adverse effects; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D019162:Anesthetics, Combined; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D007530:Isoflurane; D053148:Caspase 3; D009609:Nitrous Oxide; D000109:Acetylcholine; D004298:Dopamine