Effects of thyrotrophin-releasing hormone tartrate and its sustained release formulation on cerebral glucose metabolism in aged rats.
The effects of a sustained release formulation of thyrotrophin-releasing hormone (TRH) over two weeks (TRH-SR, 10 or 50 mg kg-1, equivalent to 0.56 or 2.80 mg kg-1 free TRH, respectively) and repeated treatment with TRH tartrate (TRH-T, 0.3, 1.0 or 3.0 mg kg-1, equivalent to 0.2, 0.7 or 2.0 mg kg-1 free TRH, respectively) on the rate of local cerebral glucose utilization (LCGU) were investigated using the quantitative autoradiographic 2-deoxy-[14C]D-glucose method in various brain regions of aged rats. In aged rats (28 months old), the LCGU was significantly reduced as compared with young adult rats (3 months old), while treatment with TRH-SR ameliorated the reduction of the LCGU in a dose-dependent manner. The brain regions ameliorated by TRH-SR were the auditory cortex, septal nucleus, substantia nigra, cerebellar cortex and cerebellar nucleus. In contrast, once-daily repeated treatment over one week with TRH-T at a dose of 0.3 mg kg-1 (equivalent to 50 mg kg-1 of TRH-SR) had no effect on the reduced LCGU in various brain regions in aged rats (27 months old), whereas treatment with a higher dose of TRH-T (0.7 or 2.0 mg kg-1 free TRH) significantly ameliorated the reduction. The comparison of the ameliorating potencies between TRH-T and TRH-SR indicated that TRH-SR had a potency about 7 times greater than TRH-T.
Nakayama
T
T
Pharmaceutical Research Laboratories I, Takeda Chemical Industries Ltd, Osaka, Japan. Nakayama_Takahiro@takeda.co.jp
Nagai
Y
Y
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003692:Delayed-Action Preparations; D005947:Glucose / Q000378:metabolism*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D003692:Delayed-Action Preparations; D013973:Thyrotropin-Releasing Hormone; D005947:Glucose