1FSBI “RIPCM FMBA”, Moscow, Russia, 2FSBI IHNA&NPh RAS, Moscow, Russia; 3Khetagurov North-Ossetian State University, Vladikavkaz, Russia; 4Lomonosov Moscow State University, Moscow, Russia
Lead diacetate induces neurotoxic effect on the brain, and its mechanisms are studied extensively. There are many regions with increased heavy metals level in environment. The learning of heavy metals and clinical drugs combined influence on brain structures is an important practical task. The aim of this study was to investigate the influence of lead diacetate, immunomodulatory drug tactivin and nootropic drug piracetam, as well as combination of lead diacetate with either tactivin or piracetam on the structure-functional state of brain structures placed on +0.95 mm from bregma (Paxinos, Watson, 2005) level. As a marker of cell state, early gene c-fos expression level (immunohistochemical method) was used.
For research 6 groups of Wistar male rats were used (n=7 in each). The following drugs were chronically (15 days) injected i.p.: to group 1 – saline, to group 2 – tactivin (0,4mg/kg), to group 3 – piracetam (300mg/kg). To groups 4, 5 and 6 – lead diacetate (10-7 mol/L), and through 4 hours – saline, tactivin and piracetam respectively. Frontal sections were stained by standard immunohistochemical method using primary antibody to c-fos (rabbit anti-rat, Santa Cruz Biotechnology inc.) and secondary fluorescent antibody (goat anti-rabbit IgG (H+L), Alexa Fluor 488). Visually-rank analysis of area and fluorescent intensity of c-fos expression in cingulate and motor cortex, substantia innominata, piriform cortex, lateral and central septal nucleus, caudate nucleus and nucleus accumbens was carried out. Statistical analysis of data was performed by ANOVA (post-hoc Fisher test).
Injection of tactivin induced increase of area and/or fluorescent intensity in lateral septal nucleus and nucleus accumbens. Piracetam increased this parameter in substantia innominata and lateral septal nucleus. Lead diacetate increased them in cingulate and motor cortex and central septal nucleus. Injection of tactivin with heavy metal change the fluorescent level in all studied structures except for piriform cortex and nucleus accumbens as compared to saline injection; and increased this parameter still more in cingulate cortex, substantia innominata and caudate nucleus as compared to lead diacetate injection. Piracetam under lead diacetate injection increased c-fos expression in cingulate cortex and substantia innominata as compared to saline injection, and at the same time decreased this parameter in motor cortex and lateral septal nucleus as compared to lead diacetate injection.
Thus c-fos expression in brain was enhanced under injection of all three drugs. The changes under injection of all drugs were observed in different structures, so they were specific. Tactivin under lead diacetate injection is the prepotent activator of previously mentioned brain structures as compared to piracetam. Probably the action of tactivin and piracetam on brain under lead diacetate injection is realized by different ways.