Regulation of NGF and NT-3 protein expression in peripheral targets by sympathetic input

Abstract

Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are target-derived proteins that regulate innervating sympathetic neurons. Here, we used western blot analysis to investigate changes in NGF and NT-3 protein in several peripheral tissues following loss of sympathetic input. Following removal of the superior cervical ganglion (SCG), large molecular weight (MW) NGF species, including proNGF-A, were increased in distal intracranial SCG targets, such as pineal gland and extracerebral blood vessels (bv). Mature NGF was a minor species in these tissues and unchanged following sympathectomy. Large MW NGF species also were increased when sympathectomy was followed by in vivo NGF administration. Mature NT-3, which was abundant in controls, was significantly decreased in these targets following sympathetic denervation. The decrease in mature NT-3 was enhanced following NGF administration. The trigeminal ganglion, which provides sensory input to these targets, showed increased NGF, but decreased NT-3, in these treatments, demonstrating that decreased NT-3 at the targets did not result from enhanced NT-3 uptake. Unlike pineal gland and extracerebral bv, the external carotid artery, an extracranial proximal SCG target, showed no change in NGF following denervation, and mature NT-3 was significantly increased. Following NGF administration, NT-3 was significantly decreased. We provide evidence for sympathetic regulation of NGF and NT-3 in peripheral targets and that elevated NGF can depress NT-3. The differential response in distal and proximal adult targets is consistent with the idea that neurons innervating proximal and distal targets may serve different roles in regulating neurotrophin protein. In addition, we conclude that previous ELISA results showing increased NGF protein following sympathetic denervation may have resulted from increases in large MW species, rather than an increase in mature NGF.

WITHDRAWN: Neurotrophins and specific receptors in the oviduct tracts of Japanese quail (Coturnix coturnix japonica)

“…Western blotting analysis revealed the presence of pro and mature forms of NGF and BDNF in all tracts, similarly to results reported in the uterus of mammals (Li et al, 2012;Wessels et al, 2014), and only one band corresponding to proNT-3, as described in pineal glands, extracerebral blood vessels and external carotid (Randolph et al, 2007). With regard to Trks, in the oviduct TrkA showed a molecular weight of 80 kDa, consistent with the molecular weight of non-glycosylated full length receptor.…”

Upregulation of BDNF and NGF in Cervical Intervertebral Discs Exposed to Painful Whole-Body Vibration

“…Further, pro-NGF protein increases only slightly after WBV, while, the high molecular weight 75kDa NGF species exhibits a robust (10-fold) (Figure 3). Although this higher molecular weight species has not been previously reported in the disc, it is prevalent in extracerebral blood vessels and the external carotid artery [39]. Freemont et al (2002) reported microvascular blood vessels expressing NGF adjacent to ingrown nerves in painful human lumbar IVDs [9].…”

Effect of 1α,25‐dihydroxyvitamin D3 in embryonic hippocampal cells

“…of NGF, corresponding to 13.5 KDa, is a minor species whereas higher molecular weight species (22)(23)(24)34,55,and 75 KDa) are predominant (Randolph et al, 2007), we have further analyzed the expression of different forms of NGF in hippocampal cells. Our experiments showed in untreated samples different abundance of 75 KDa, 34 KDa, and 13 KDa NGF species in NFL and purified nuclei.…”

“…The increase of the mature form could explain the differentiating effects of vitamin D3. Little is known on the function of the 75 KDa species, although an increase after denervation has been found (Randolph et al, 2007). One of the roles of the increased NGF could be the increase in the expression of neurofilaments, proteins that play a key role in the maintenance and remodeling of the neuronal cytoskeleton (Vaucher et al, 2001).…”