Department of Zoology, Pineal Research Lab, Banaras Hindu University, Varanasi - 221005, India.
Immun Ageing. 2009 Apr 23;6:5. doi: 10.1186/1742-4933-6-5.
Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) - a beta adrenergic blocker, is known to perform chemical pinealectomy (Px) by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT) for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult and aged seasonal breeder Indian palm squirrel Funambulus pennanti.
Aged squirrel presented reduced immune parameters (i.e. total leukocyte count (TLC), Lymphocytes Count (LC), % stimulation ratio of splenocytes (% SR) against T cell mitogen concanavalin A (Con A), delayed type hypersensitivity (DTH) to oxazolone) when compared to young adult group. Melatonin administration (25 microg/100 g body mass/day) significantly increased the immune parameters in aged more than the young adult squirrel while PCPA administration (4.5 mg/100 g body mass/day) reduced all the immune parameters more significantly in young than aged. Combination of PCPA and melatonin significantly increased the immune parameters to the normal control level of both the age groups. TBARS level was significantly high in aged than the young group. PCPA treatment increased TBARS level of young and aged squirrels both while melatonin treatment decreased it even than the controls. Nighttime peripheral melatonin level was low in control aged group than the young group. Melatonin injection at evening hours significantly increased the peripheral level of nighttime melatonin, while combined injection of PCPA and melatonin brought it to control level in both aged and young adult squirrels.
PCPA suppressed immune status more in aged than in adult by reducing melatonin level as it did chemical Px. Melatonin level decreased in control aged squirrels and so there was a decrease in immune parameters with a concomitant increase in free radical load of spleen. Decreased immune status can be restored following melatonin injection which decreased free radical load of spleen and suggest that immune organs of aged squirrels were sensitive to melatonin. Increased free radical load and decreased peripheral melatonin could be one of the reasons of immunosenescence.
我们的兴趣在于发现松果腺及其通过褪黑素作为免疫衰老的调节剂。对氯苯丙氨酸(PCPA) - β肾上腺素能阻滞剂,通过间接抑制褪黑素合成的基质 5-羟色胺(5-HT)和褪黑素本身来执行化学松果腺切除术(Px)。PCPA 单独和与褪黑素联合作用于免疫调节和脾脏中年轻成年和季节性繁殖的印度棕榈松鼠 Funambulus pennanti 的自由基负荷的作用。
与年轻成年组相比,老年松鼠的免疫参数(即总白细胞计数(TLC)、淋巴细胞计数(LC)、脾细胞对 T 细胞有丝分裂原刀豆蛋白 A(Con A)的刺激比(%SR)、迟发型超敏反应(DTH)对恶唑酮)降低。褪黑素给药(25μg/100g 体重/天)显著增加了老年松鼠的免疫参数,而 PCPA 给药(4.5mg/100g 体重/天)则显著降低了年轻和老年松鼠的所有免疫参数。PCPA 和褪黑素的组合使两组的免疫参数显著增加到正常对照水平。TBARS 水平在老年组中明显高于年轻组。PCPA 处理增加了年轻和老年松鼠的 TBARS 水平,而褪黑素处理甚至比对照组降低了它。夜间外周褪黑素水平在对照组老年组中低于年轻组。褪黑素在晚上注射显着增加了外周夜间褪黑素水平,而 PCPA 和褪黑素的联合注射使两者在老年和成年松鼠中均达到对照水平。
PCPA 通过降低褪黑素水平来抑制衰老状态下的免疫状态,这比成年状态下更明显,因为它执行了化学 Px。对照老年松鼠的褪黑素水平下降,因此免疫参数下降伴随着脾脏自由基负荷增加。在注射褪黑素后,免疫状态可以恢复,降低了脾脏的自由基负荷,并表明老年松鼠的免疫器官对褪黑素敏感。增加的自由基负荷和外周褪黑素的减少可能是免疫衰老的原因之一。