The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods

The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by... Nerve growth factor (NGF) is essential for the survival and functional maintenance of forebrain cholinergic neurons projecting mainly to the cortex and hippocampus. NGF is produced in these brain areas but while mature NGF (mNGF) has a survival/differentiative effect its precursor proNGF elicits apoptosis in cholinergic neurons. Impaired neurotransmission, loss of cholinergic phenotype and abnormal NGF content characterize the cholinergic circuitries in animal models of diabetic encephalopathy (DE). It is not known whether defective production or maturation of NGF could play a key role in cholinergic neurodegeneration in DE. Quantification of the mNGF/proNGF ratio is therefore needed to characterize the development and progression of NGF-related neuronal diseases. In our work, we aimed at developing ELISA methods to measure either mNGF or proNGF tissue concentration; and to define the mNGF/proNGF ratio in the rat cortex and hippocampus during the early stage of streptozotocin-induced type 1 diabetes. Using commercially available NGF ELISA kits and antibodies, we set up ELISAs for human and rat mNGF and proNGF. We then analyzed the mNGF/proNGF ratio in the cortex and hippocampus of DE rats and found that it decreased in both tissues starting from the fourth week after diabetes induction. In diabetic brain the increase in proNGF involves accumulation of the isoforms with molecular weights of 50 and 34kDa. Our study for the first time specifically quantifies the absolute content of mature and proNGF and the mNGF/proNGF ratio in brain tissues, suggesting that early progression of experimental DE is characterized by defective maturation of NGF. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

The mature/pro nerve growth factor ratio is decreased in the brain of diabetic rats: Analysis by ELISA methods

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier B.V.
ISSN
0006-8993
D.O.I.
10.1016/j.brainres.2015.08.005
Publisher site
See Article on Publisher Site

Abstract

Nerve growth factor (NGF) is essential for the survival and functional maintenance of forebrain cholinergic neurons projecting mainly to the cortex and hippocampus. NGF is produced in these brain areas but while mature NGF (mNGF) has a survival/differentiative effect its precursor proNGF elicits apoptosis in cholinergic neurons. Impaired neurotransmission, loss of cholinergic phenotype and abnormal NGF content characterize the cholinergic circuitries in animal models of diabetic encephalopathy (DE). It is not known whether defective production or maturation of NGF could play a key role in cholinergic neurodegeneration in DE. Quantification of the mNGF/proNGF ratio is therefore needed to characterize the development and progression of NGF-related neuronal diseases. In our work, we aimed at developing ELISA methods to measure either mNGF or proNGF tissue concentration; and to define the mNGF/proNGF ratio in the rat cortex and hippocampus during the early stage of streptozotocin-induced type 1 diabetes. Using commercially available NGF ELISA kits and antibodies, we set up ELISAs for human and rat mNGF and proNGF. We then analyzed the mNGF/proNGF ratio in the cortex and hippocampus of DE rats and found that it decreased in both tissues starting from the fourth week after diabetes induction. In diabetic brain the increase in proNGF involves accumulation of the isoforms with molecular weights of 50 and 34kDa. Our study for the first time specifically quantifies the absolute content of mature and proNGF and the mNGF/proNGF ratio in brain tissues, suggesting that early progression of experimental DE is characterized by defective maturation of NGF.

Journal

Brain ResearchElsevier

Published: Oct 22, 2015

References

  • Increased NGF proforms in aged sympathetic neurons and their targets
    Bierl, M.A.; Isaacson, L.G.
  • Modification of lymphoid and brain nerve growth factor levels in systemic lupus erythematosus mice
    Bracci-Laudiero, L.
  • Neuroprotective effect of N-acetylcysteine in the development of diabetic encephalopathy in streptozotocin-induced diabetes
    Kamboj, S.S.; Chopra, K.; Sandhir, R.
  • Brain cholinergic markers and tau phosphorylation are altered in experimental type 1 diabetes: normalization by electroacupuncture
    Rocco, M.L.
  • Diabetes underlies common neurological disorders
    Sima, A.A.
  • Matrix remodelling enzymes, the protease cascade and glycosylation
    Van den Steen, P.E.
  • Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity
    Weinstock, M.; Shoham, S.
  • An enzyme-linked immunoassay for nerve growth factor (NGF): a tool for studying regulatory mechanisms involved in NGF production in brain and in peripheral tissues
    Weskamp, G.; Otten, U.

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