TY - JOUR
T1 - Dentate granule neuron apoptosis and glia activation in murine hippocampus induced by trimethyltin exposure
AU - Fiedorowicz, Anna
AU - Figiel, Izabela
AU - Kamińska, Boena
AU - Zaremba, Malgorzata
AU - Wilk, Sherwin
AU - Oderfeld-Nowak, Barbara
N1 - Funding Information:
This work was partly supported by grant 4 P05A 04315 from State Committee for Scientific Research to B.O.N., grant 4 P05A 0008 18 from State Committee for Scientific Research to I.F. and grant from State Committee for Scientific Research to the Nencki Institute. We are grateful to Dr. L. Aloe for his kind gift of NGF antibody. Mrs. T. Szczesna’s skillful technical assistance is appreciated.
PY - 2001/9/7
Y1 - 2001/9/7
N2 - We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on murine hippocampal neurons and glial cells. Three days following intraperitoneal (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body weight we detected damage of the dentate gyrus granular neurons. The dying cells displayed chromatin condensation and internucleosomal DNA fragmentation, which are the most characteristic features of apoptosis. To study, if prolyl oligopeptidase is engaged in neuronal apoptosis following TMT administration, we pretreated mice with the specific inhibitor - Fmoc-Pro-ProCN in doses of 5 and 10 mg/kg body weight (i.p. injection). Three days following injection we did not observe any attenuation of neurotoxic damage, regardless of inhibitor dose, indicating the lack of prolyl oligopeptidase contribution to neuronal injury caused by TMT. The neurodegeneration was associated with reactive astrogliosis in whole hippocampus, but particularly in injured dentate gyrus. The reactive astrocytes showed an increased nerve growth factor (NGF) expression in ventral as well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in neurons of CA3/CA4 areas, which were almost totally spared after TMT intoxication. It suggested a role for this neurotrophin in protection of pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields. The granule neurons' death was accompanied by increased histochemical staining with isolectin B4, a marker of microglia, in the region of neurodegeneration. The microglial cells displayed ramified and ameboid morphology, characteristic of their reactive forms. Activated microglia were the main source of interleukin 1β (IL-1β). It is possible that this cytokine may participate in neurodegeneration of granule cells. Alternatively, IL-1β elaborated by microglia could play a role in increasing NGF expression, both in astroglia and in CA3/CA4 neurons.
AB - We investigated the effect of trimethyltin (TMT), a well-known neurotoxicant, on murine hippocampal neurons and glial cells. Three days following intraperitoneal (i.p.) injection of TMT into 1-month-old Balb/c mice at a dose of 2.5 mg/kg body weight we detected damage of the dentate gyrus granular neurons. The dying cells displayed chromatin condensation and internucleosomal DNA fragmentation, which are the most characteristic features of apoptosis. To study, if prolyl oligopeptidase is engaged in neuronal apoptosis following TMT administration, we pretreated mice with the specific inhibitor - Fmoc-Pro-ProCN in doses of 5 and 10 mg/kg body weight (i.p. injection). Three days following injection we did not observe any attenuation of neurotoxic damage, regardless of inhibitor dose, indicating the lack of prolyl oligopeptidase contribution to neuronal injury caused by TMT. The neurodegeneration was associated with reactive astrogliosis in whole hippocampus, but particularly in injured dentate gyrus. The reactive astrocytes showed an increased nerve growth factor (NGF) expression in ventral as well as dorsal hippocampal parts. NGF immunoreactivity was also augmented in neurons of CA3/CA4 areas, which were almost totally spared after TMT intoxication. It suggested a role for this neurotrophin in protection of pyramidal cells from loss of connection between CA3/CA4 and dentate gyrus fields. The granule neurons' death was accompanied by increased histochemical staining with isolectin B4, a marker of microglia, in the region of neurodegeneration. The microglial cells displayed ramified and ameboid morphology, characteristic of their reactive forms. Activated microglia were the main source of interleukin 1β (IL-1β). It is possible that this cytokine may participate in neurodegeneration of granule cells. Alternatively, IL-1β elaborated by microglia could play a role in increasing NGF expression, both in astroglia and in CA3/CA4 neurons.
KW - Dentate granule neuron apoptosis
KW - Gliosis
KW - IL-1β
KW - NGF
KW - Prolyl oligopeptidase
KW - Trimethyltin
UR - http://www.scopus.com/inward/record.url?scp=0035823375&partnerID=8YFLogxK
U2 - 10.1016/S0006-8993(01)02675-0
DO - 10.1016/S0006-8993(01)02675-0
M3 - Article
C2 - 11532427
AN - SCOPUS:0035823375
SN - 0006-8993
VL - 912
SP - 116
EP - 127
JO - Brain Research
JF - Brain Research
IS - 2
ER -