TY - JOUR
T1 - Altered levels and splicing of the amyloid precursor protein in the adult rat hippocampus after treatment with DMSO or retinoic acid
AU - Pan, Jia Bao
AU - Monteggia, Lisa M
AU - Giordano, Tony
PY - 1993/5
Y1 - 1993/5
N2 - Alzheimer's disease and cognitive impairment in rats has been associated with an increase in the percentage of amyloid precursor protein (APP) containing the KPI domain. It has recently been reported that retinoic acid (RA) is capable of increasing the levels and altering the splicing ratio of APP in cultured SH-SY5Y cells. The effects of peripherally administered RA (64 or 640 μg/kg; i.p.; q.d.) on the abundance of APP, the ratio of the three major isoforms, and the relative abundance of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined by rtPCR in the hippocampus of aged rats. Corresponding changes in choline acetyltransferase (ChAT) activity were also measured. Vehicle (DMSO) treated rats exhibited a 2× (P < 0.01) increase in total APP and an 8× (P < 0.001) decrease in the cyclophilin transcript. In addition, DMSO increased the percentage of APP 695 from 89% in saline treated rats to 94%. Treatment of RA in DMSO decreased the accumulation of total APP relative to cyclophilin at both the low (6.4×; P < 0.01) and high (8×; P < 0.05) dosages when compared to DMSO treated rats. Furthermore, the level of APP-695 decreased to 82% with low dosage of RA and 75% at high dosage of the total APP transcripts. No significant change in either NGF, NT-3, or BDNF transcripts were observed following low or high dosage RA administration relative to cyclophilin RNA nor was a change in ChAT activity detected at either of the dosages tested. These results demonstrate that both DMSO and RA are capable of altering APP accumulation and splicing in distinct manners.
AB - Alzheimer's disease and cognitive impairment in rats has been associated with an increase in the percentage of amyloid precursor protein (APP) containing the KPI domain. It has recently been reported that retinoic acid (RA) is capable of increasing the levels and altering the splicing ratio of APP in cultured SH-SY5Y cells. The effects of peripherally administered RA (64 or 640 μg/kg; i.p.; q.d.) on the abundance of APP, the ratio of the three major isoforms, and the relative abundance of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) were determined by rtPCR in the hippocampus of aged rats. Corresponding changes in choline acetyltransferase (ChAT) activity were also measured. Vehicle (DMSO) treated rats exhibited a 2× (P < 0.01) increase in total APP and an 8× (P < 0.001) decrease in the cyclophilin transcript. In addition, DMSO increased the percentage of APP 695 from 89% in saline treated rats to 94%. Treatment of RA in DMSO decreased the accumulation of total APP relative to cyclophilin at both the low (6.4×; P < 0.01) and high (8×; P < 0.05) dosages when compared to DMSO treated rats. Furthermore, the level of APP-695 decreased to 82% with low dosage of RA and 75% at high dosage of the total APP transcripts. No significant change in either NGF, NT-3, or BDNF transcripts were observed following low or high dosage RA administration relative to cyclophilin RNA nor was a change in ChAT activity detected at either of the dosages tested. These results demonstrate that both DMSO and RA are capable of altering APP accumulation and splicing in distinct manners.
KW - Amyloid precursor protein
KW - Dimethyl sulfoxide
KW - Retinoic acid
KW - Reverse transcriptase PCR
KW - Splicing
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U2 - 10.1016/0169-328X(93)90198-X
DO - 10.1016/0169-328X(93)90198-X
M3 - Article
C2 - 7684485
AN - SCOPUS:0027231768
SN - 0169-328X
VL - 18
SP - 259
EP - 266
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 3
ER -