ABSTRACT
Analysis of BDNF (Brain Derived Neurotrophic Factor) expression in an experimental model of chronic renal failure conditions.
The Brain Derived Neurotrophic Factor is the most largely diffused member of neurotrophins in the development and adult mammal brain. The BDNF is involved in the synaptic plasticity, in neuronal survival and differentiation both in the central nervous system and in the peripheral one. The BDNF’s actions are dued to its link with a particular receptor and to the generation of a signal transduction pathways that takes to the activation of the ERK (extracellular signal regulated protein kinase), pathway that modulars the factors of transcription that modifies genic expression. The neurotrophins are studied in order to comprehend their physiological role and their probable involvement in the pathogenesis about several neurological disorders such as Alzheimer disease, Parkinson disease and more recently depression; among genders wherein there is a large insurgence of depression there is that kidney failure and hemodialysis patients.
AIM OF STUDY: The aim of this research is to investigate the physiopathological role of BDNF in chronic renal failure conditions.
MATERIALS AND METHODS: The sperimental phase has been carried out about 12 Winstar femail rats, that are subdivided in two groups: control rats and nefrectomia rats. Nx rats are submitted to operative procedure of nefrectomia 5/6 with removal right kidney and subsequent resection of upper and low left polos (corresponding about 2/3 of tissue). The control rats had undergone the same operative procedure but without renal tissue removal. All animals has been placed in metabolic cages and their urine have been picked up before operative procedure and before sacrifice similarly have been done for the body weights. At the end of the sperimental period (10 weeks), the animals have been sacrified and have been picked up patterns of serum, plasma, liquor, renal tissue, prefrontal cortex and hippocampus. The patterns of urine and plasma have been used in order to value the levels of creatinina and proteinuria. The kidneys have been
included in liquid paraffin for the arrangement of istologic producions with Pas. The patterns of prefrontal cortex and hippocampus have been homogenized to value the levels of central BDNF. The BDNF have been dosed in patterns of liquor, serum, and urine too. For the analysis of BDNF have been exploited the BDNF Emax Immunoassay ELISA emploing appropiate kit (Promega USA) following the protocols treating of constructor.
RESULTS: In the six animals of Nx group has been observed a decrese of the body weight (228,83±24,29 gr. vs 301,41 ±18,67 gr. in the control group; p<0,05) a decrease of a renal functionality as is evident of decrese of clearance creatinina (0,1561±0,048 vs 1,1423±0,0684 in the control group; p<0,05) and of proteinuria (24,970±11,001 mg. tot. prot. vs 8,1518±1,2265 mg. tot prot. in the control group; p<0,05). These results are confirmed also of the istologic study of the products of kidney that showed the classic form of the glomerular fibrous and interstice with atrophy of the tubular epithelium. As far as the peripheral levels of BDNF in the urine there is a decrease (29,242±22,583 pg/mg prot. vs 90,342±99,396 pg/mg prot. in the control group) and likewise in the plasma (228,75±90,78 pg/ml vs 429,71±377,48 pg/ml in the control group) while the total circulating levels of sirum are unchanged (1346,6±105,8 pg/ml vs 1350,6±186,6 pg/ml in the control group). At the central level in the liquor the BDNF reduces significantly (78,81±16,65 pg/ml vs 128,14±37,09 pg/ml in the control group; p<0,05) as well as in the cortex (28,25±19,82 pg/mg prot vs 66,27±8,19 pg/mg prot in the control group; p<0,05) while in the hippocampus has been observed a significantly increase (238,1±65,6 pg/mg prot vs 88,9±42,79 pg/mg prot in the control group; p<0,05).
CONCLUSIONS: Our sperimental model of IRC in the rat proves as the disease of renal capacity is correlated to a neurological pathological type similar to that observed in animal model of depression. In fact the alteration of renal function is associated to a decrease of urinary, plasmatic, of liquor and cortical levels. On an hippocampal level has been observed an important
increase of BDNF since the central activity of the prefrontal cortex and the hippocampus are functionally anatomically tightly linked and this last aspect could be affect the result offsetting response in the presence of a functional cortical change.
