Effects of intranasally-delivered pro-nerve growth factors on the septo-hippocampal system in healthy and diabetic rats. (1st October 2020)

• Record Type: Journal Article
• Authors: Soligo, Marzia; Protto, Virginia; Chiaretti, Antonio; Piccinin, Sonia; De Stefano, Maria Egle; Nisticò, Robert; Bracci-Laudiero, Luisa; Manni, Luigi
• Is Part Of: Neuropharmacology. Volume 176(2020)
• Publication Date: 2020-10-01
• Subjects: pro nerve growth factor (proNGF) -- Hippocampal neurogenesis -- Dentate-gyrus long-term potentiation (DG-LTP) -- Cholinergic system -- Diabetes -- Rat; NGF nerve growth factor -- mNGF mature nerve growth factor -- proNGF pro-nerve growth factor -- TrkA Tropomyosin Receptor Kinase A -- p75NTR p75 neurotrophin receptor -- DE diabetic encephalopathy -- AD Alzheimer's disease -- DG-LTP dentate gyrus long-term potentiation -- SMG submaxillary glands -- STZ streptozotocin -- BFCN basal forebrain cholinergic neurons -- ChAT choline acetyl transferase; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2020.108223
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Pro-nerve growth factor (proNGF) is the predominant form of NGF in the brain and its levels increase in neurodegenerative diseases. The balance between NGF receptors may explain the contradictory biological activities of proNGF. However, the specific role of the two main proNGF variants is mostly unexplored. proNGF-A is prevalently expressed in healthy brain, while proNGF-B content increases in the neuro-degenerating brain. Recently we have investigated in vitro the biological action of native mouse proNGF variants. To gain further insights into the specific functions of the two proNGFs, here we intranasally delivered mouse-derived proNGF-A and proNGF-B to the brain parenchyma of healthy and diabetic rats, the latter characterized by dysfunction in spatial learning and memory, in the septo-hippocampal circuitry and by relative increase in proNGF-B hippocampal levels. Exogenous proNGF-B induces depression of hippocampal DG-LTP and impairment of hippocampal neurogenesis in healthy animals, with concomitant decrease in basal forebrain cholinergic neurons and cholinergic fibers projecting to the hippocampus. proNGF-A, while ineffective in healthy animals, rescues the diabetes-induced impairment in DG-LTP and hippocampal neurogenesis, promoting the concomitant recovery of the basal forebrain cholinergic phenotype. Our experimental evidences suggest that the balance between different proNGFs may influence the development and progression of neurodegenerative diseases. Graphical abstract: Image 1 Highlights: Native mouse proNGF-A/-B were delivered to the rat brain via intranasal route. proNGF-A improves DG-LTP and SGZ-neurogenesis in rat with diabetic encephalopathy. proNGF-A rescues the diabetes-impaired cholinergic phenotype in the medial septum. proNGF-B depress DG-LTP and impairs SGZ-neurogenesis in healthy rats. proNGF-B impairs cholinergic phenotype and neurotransmission in healthy rats.