Effect of intranasal NGF administration in injured spinal cord and leptin levels in adult rats

Abstract

spinal cord injury alters a number of endogenous biological signals known to be involved in the modulation of neurotrophic and neuroprotective events. nerve growth factor (ngF) is a neurotrophic factor expressed in neuronal and non-neuronal tissues including spinal cord, and increases after spinal cord injury. Recent findings revealed that leptin, an adipocyte-derived cytokine (adipokine), enhance neuronal survival and exert neuroprotective action, and played an important role in nociceptive behavior induced by nerve injury. Whether ngF affects the expression of leptin in injured spinal cord has not been investigated. The present study was designed to evaluate: (i) whether intranasal ngF administration reached the spinal cord of the rat, (ii) if ngF affects the expression of leptin in the spinal cord and adipose tissue, and (iii) whether intranasal ngF affects the behavioral and spinal cord neuronal deficits induced by spinal cord injury. The result showed that intranasal ngF enhances the expression of (i) ngF and ngF-receptors (Trka and p75 nTR) in injured spinal cord exerting behavioral and neuroprotective action, and (ii) leptin in injured spinal cord and in subcutaneous (white) and interscapular (brown) adipose tissue. altogether, the present data demonstrate the efficacy of intranasal administration of ngF, and suggest a link between the neurotrophin ngF and the adipokine leptin that may be therapeutically explored in injured spinal cord.

Intranasal Delivery of Nerve Growth Factor in Neurodegenerative Diseases and Neurotrauma

“…Other relevant models of neurological pathologies in which the efficacy of IN-NGF has been attempted, include cerebral ischemia, traumatic lesions of the brain and spinal cord, epilepsy, amyotrophic lateral sclerosis, hypogonadism related to premature aging, and depression. Also in these models, IN-NGF improved selective behavioral performances (Cheng et al, 2009;Shi et al, 2010;Bianchi et al, 2012;Tian et al, 2012;Aloe et al, 2014;Zhong et al, 2017), Aβ plaque deposition and tau phosphorylation (Tian et al, 2012;Lv et al, 2014), and promoted anti-inflammatory response (Lv et al, 2013). It also decreased seizure onset (Lei et al, 2017), counteracted diseaseinduced apoptosis (Cheng et al, 2009;Lv et al, 2013;Lei et al, 2017), enhanced VEGF and endothelial cell migration (Li et al, 2018), enhanced neurogenesis (Cheng et al, 2009;Zhu et al, 2011), regulated hypothalamic gonadotropin releasing hormone production (Luo et al, 2018).…”

Computational modelling: moonlighting on the neuroscience and medicine

“…Nerve growth factor (NGF), the prototypic member of the neurotrophin family of growth factors, which was discovered by the Nobel Laureate, Rita Levi-Montalcini, plays a pivotal role in neuronal cell growth and differentiation in both peripheral and central nervous systems in health and disease (28,29). Furthermore, NGF is implicated in (i) the mechanism of action of a wide range of psychotropic agents (30)(31)(32)(33)(34), and (ii) the therapeutic effect in neuropsychiatric and cardiometabolic diseases (29,(35)(36)(37). Since the mechanisms underlying the formation of complex neural networks have not been fully understood, the methods of statistical mechanics have been recently applied to extract predictions for cellular signalling networks.…”