Tehrani M H, Tate C A, al-Dahan M I
Department of Biochemistry, Baylor College of Medicine, Houston, TX 77030, USA.
Neurobiol Aging. 1995 Mar-Apr;16(2):199-204. doi: 10.1016/0197-4580(94)00158-8.
We examined gamma-aminobutyric acid (GABA), benzodiazepine and convulsant sites of postsynaptic GABA/benzodiazepine receptors (GBZR) in cerebral membranes of inbred Fischer 344 male rats as a function of age. In aged rats (23 to 24 months), the benzodiazepine binding site as determined by [3H]flunitrazepam was 47% and 43% lower than corresponding values in young adult (3 to 4 months) and mature (10 to 12 months) rats, respectively. The decrease was due to the loss of binding density rather than a change in affinity. No statistically significant age-related changes in [3H]muscimol binding were observed when 5 nM or 40 nM labeled muscimol were used. GABA produced a dose-dependent stimulation of flunitrazepam binding in all age groups, but the maximum stimulation in aged animals was significantly higher (24%) than in young and mature animals. The [35S]TBPS binding site, the convulsant site of GABA/benzodiazepine receptors, was unaffected with age. We also studied the effects of exercise on GBZR binding sites of aged rats. The decline of flunitrazepam binding sites and the high sensitivity of flunitrazepam binding to regulation by GABA in aged animals were reversed by 8 to 10 weeks of endurance exercise. Endurance exercise did not have any significant effect on muscimol or TBPS binding sites. Results suggest that there are aged-related alterations of GBZR binding sites and that these modifications can be reversed by exercise.
我们研究了近交系Fischer 344雄性大鼠脑膜中突触后γ-氨基丁酸（GABA）、苯二氮䓬和惊厥性GABA/苯二氮䓬受体（GBZR）位点随年龄的变化情况。在老年大鼠（23至24个月）中，由[³H]氟硝西泮测定的苯二氮䓬结合位点分别比年轻成年大鼠（3至4个月）和成熟大鼠（10至12个月）的相应值低47%和43%。这种降低是由于结合密度的丧失而非亲和力的改变。当使用5 nM或40 nM标记的蝇蕈醇时，未观察到与年龄相关的[³H]蝇蕈醇结合的统计学显著变化。GABA在所有年龄组中均产生剂量依赖性的氟硝西泮结合刺激作用，但老年动物中的最大刺激作用明显高于年轻和成熟动物（高24%）。GABA/苯二氮䓬受体的惊厥性位点[³⁵S]TBPS结合位点不受年龄影响。我们还研究了运动对老年大鼠GBZR结合位点的影响。8至10周的耐力运动可逆转老年动物中氟硝西泮结合位点的下降以及氟硝西泮结合对GABA调节的高敏感性。耐力运动对蝇蕈醇或TBPS结合位点没有任何显著影响。结果表明，GBZR结合位点存在与年龄相关的改变，并且这些改变可通过运动逆转。
