scholarly journals Intrahippocampal Adeno-Associated Virus–Mediated Overexpression of Nerve Growth Factor Reverses 192IgG-Saporin–Induced Impairments of Hippocampal Plasticity and Behavior

2021 ◽  
Vol 15 ◽  
Author(s):  
Yulia V. Dobryakova ◽  
Yulia S. Spivak ◽  
Maria I. Zaichenko ◽  
Alena A. Koryagina ◽  
Vladimir A. Markevich ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Long Term Potentiation ◽  
Septal Area ◽  
Adeno Associated Virus ◽  
Walking Test ◽  
Nerve Growth ◽  
Cholinergic Deficit ◽  
Beneficial Effects ◽  
Y Maze

One of the aspects of Alzheimer disease is loss of cholinergic neurons in the basal forebrain, which leads to development of cognitive impairment. Here, we used a model of cholinergic deficit caused by immunotoxin 192IgG-saporin to study possible beneficial effects of adeno-associated virus (AAV)–mediated overexpression of nerve growth factor (NGF) in the hippocampus of rats with cholinergic deficit. Suspension of recombinant AAV carrying control cassette or cassette with NGF was injected into both hippocampi of control rats or rats with cholinergic deficit induced by intraseptal injection of 192IgG-saporin. Analysis of choline acetyltransferase (ChAT) immunostaining showed that NGF overexpression in the hippocampus did not prevent strong loss of ChAT-positive neurons in the septal area caused by the immunotoxin. Induction of cholinergic deficit in the hippocampus led to impairments in Y-maze and beam-walking test but did not affect behavioral indices in the T-maze, open field test, and inhibitory avoidance training. NGF overexpression in the rats with cholinergic deficit restored normal animal behavior in Y-maze and beam-walking test. Recording of field excitatory postsynaptic potentials in vivo in the hippocampal CA1 area showed that induction of cholinergic deficit decreased magnitude of long-term potentiation (LTP) and prevented a decrease in paired-pulse ratio after LTP induction, and NGF overexpression reversed these negative changes in hippocampal synaptic characteristics. The beneficial effect of NGF was not associated with compensatory changes in the number of cells that express NGF receptors TrkA and NGFR in the hippocampus and medial septal area. NGF overexpression also did not prevent a 192IgG-saporin–induced decrease in the activity of acetylcholine esterase in the hippocampus. We conclude that NGF overexpression in the hippocampus under conditions of cholinergic deficit induces beneficial effects which are not related to maintenance of cholinergic function.

scholarly journals Nerve growth factor (NGF) with hypoxia response elements loaded by adeno-associated virus (AAV) combined with neural stem cells improve the spinal cord injury recovery

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qiuji Wu ◽  
Ziyue Xiang ◽  
Yibo Ying ◽  
Zhiyang Huang ◽  
Yurong Tu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Neural Stem Cells ◽  
Histochemical Staining ◽  
Adeno Associated Virus ◽  
Nerve Growth ◽  
Cord Injury

AbstractThe ischemia and hypoxia microenvironment after spinal cord injury (SCI) makes SCI repair a challenging problem. With various stimulus, chances for neural stem cells (NSCs) to differentiate into neurons, astrocytes, oligodendrocytes are great and is considered as a potential source of the stem cell therapy to SCI. Our research used adeno-associated virus (AAV) to carry the target gene to transfect neural stem cells. Transfected NSCs can express nerve growth factor (NGF) navigated by five hypoxia-responsive elements (5HRE). Therefore, the 5HRE-NGF-NSCs could express NGF specifically in hypoxia sites to promote the tissue repair and function recovery. Based on the regeneration of neurocytes and promotion of the recovery found in SCI models, via locomotor assessment, histochemical staining and molecular examinations, our results demonstrated that 5HRE-NGF-NSCs could improve the motor function, neurons survival and molecules expression of SCI rats. Meanwhile, the downregulated expression of autophagy-related proteins indicated the inhibitive effect of 5HRE-NGF-NSCs on autophagy. Our research showed that 5HRE-NGF-NSCs contribute to SCI repair which might via inhibiting autophagy and improving the survival rate of neuronal cells. The new therapy also hampered the hyperplasia of neural glial scars and induced axon regeneration. These positive functions of 5HRE-NGF-NSCs all indicate a promising SCI treatment.

Nerve growth factor inhibits the expression of long-term potentiation in hippocampal slices

Neuroreport ◽  
1993 ◽  
Vol 4 (2) ◽  
pp. 147-150 ◽  
Author(s):  
V. Tancredi ◽  
G. DʼArcangelo ◽  
D. Mercanti ◽  
P. Calissano
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
Nerve Growth ◽  
Term Potentiation

Lentiviral-mediated overexpression of nerve growth factor (NGF) prevents beta-amyloid [25–35]-induced long term potentiation (LTP) decline in the rat hippocampus

2015 ◽  
Vol 1624 ◽  
pp. 398-404 ◽  
Author(s):  
Shukhrat S. Uzakov ◽  
Andrey D. Ivanov ◽  
Sergey V. Salozhin ◽  
Vladimir A. Markevich ◽  
Natalia V. Gulyaeva
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Beta Amyloid ◽  
Long Term Potentiation ◽  
Rat Hippocampus ◽  
Nerve Growth ◽  
Term Potentiation

scholarly journals Effect of ATP-sensitive potassium channel agonists on sympathetic hyperinnervation in postinfarcted rat hearts

2009 ◽  
Vol 296 (6) ◽  
pp. H1949-H1959 ◽  
Author(s):  
Chih-Sen Kang ◽  
Chien-Chang Chen ◽  
Chih-Chan Lin ◽  
Nen-Chung Chang ◽  
Tsung-Ming Lee
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Sympathetic Innervation ◽  
Immunohistochemical Analysis ◽  
Sympathetic Nerves ◽  
Acute Administration ◽  
Nerve Growth ◽  
Beneficial Effects ◽  
Male Wistar Rats

Although the acute administration of ATP-sensitive potassium (KATP) channel agonists provides a neuroprotection, it is unclear whether similar benefits are found by modulating sympathetic innervation in chronic settings after myocardial infarction. We assessed whether KATP channel agonists can attenuate the sprouting of cardiac sympathetic nerves after infarction. Male Wistar rats after ligating coronary artery were randomized to either saline, nicorandil, pinacidil, glibenclamide, or a combination of 1) nicorandil and glibenclamide or 2) pinacidil and glibenclamide for 4 wk. To elucidate the role of mitochondrial KATP channels in modulating nerve growth factor, 5-hydroxydecanoate was assessed in an in vitro model. The measurement of myocardial norepinephrine levels revealed a significant elevation in saline-treated infarcted rats compared with sham-operated rats, consistent with excessive sympathetic innervation. Excessive sympathetic innervation was blunted after giving the rats either nicorandil or pinacidil, compared with saline, as assessed by the immunohistochemical analysis of tyrosine hydroxylase, growth associated protein-43, and neurofilament and Western blot analysis and real-time quantitative RT-PCR of nerve growth factor. The arrhythmic scores during programmed stimulation in the saline- or glibenclamide-treated infarcted rats were significantly higher than those of rats treated with KATP channel agonists. In contrast, the beneficial effects of nicorandil and pinacidil were abolished by administering either glibenclamide or 5-hydroxydecanoate. The sympathetic hyperinnervation after infarction is attenuated by the activation of mitochondrial KATP channels. The chronic use of mitochondrial KATP channel agonists after infarction may attenuate the arrhythmogenic response to programmed electrical stimulation.

scholarly journals The Nerve Growth Factor Signaling and Its Potential as Therapeutic Target for Glaucoma

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Haitao Wang ◽  
Rikang Wang ◽  
Thilini Thrimawithana ◽  
Peter J. Little ◽  
Jiangping Xu ◽  
...  
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Ganglion Cells ◽  
Tyrosine Kinase Receptor ◽  
Growth Factor Signaling ◽  
Retinal Ganglion ◽  
Nerve Growth ◽  
Therapeutic Implications ◽  
Beneficial Effects ◽  
Ngf Signaling

Neuroprotective therapies which focus on factors leading to retinal ganglion cells (RGCs) degeneration have been drawing more and more attention. The beneficial effects of nerve growth factor (NGF) on the glaucoma have been recently suggested, but its effects on eye tissue are complex and controversial in various studies. Recent clinical trials of systemically and topically administrated NGF demonstrate that NGF is effective in treating several ocular diseases, including glaucoma. NGF has two receptors named high affinity NGF tyrosine kinase receptor TrkA and low affinity receptor p75NTR. Both receptors exist in cells in retina like RGC (expressing TrkA) and glia cells (expressing p75NTR). NGF functions by binding to TrkA or p75NTR alone or both together. The binding of NGF to TrkA alone in RGC promotes RGC’s survival and proliferation through activation of TrkA and several prosurvival pathways. In contrast, the binding of NGF to p75NTR leads to apoptosis although it also promotes survival in some cases. Binding of NGF to both TrkA and p75NTR at the same time leads to survival in which p75NTR functions as a TrkA helping receptor. This review discusses the current understanding of the NGF signaling in retina and the therapeutic implications in the treatment of glaucoma.

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