Intranasal Administration of Nerve Growth Factor Produces Antidepressant-Like Effects in Animals

Abstract

Many works showed that nerve growth factor (NGF) injected into the brain of animal model emerges potential antidepressant effects. However, this route of administration significantly restricts the application of NGF clinically. Here, we reported that intranasal NGF could provide an alternative to intraventricular injection. The behavioral analysis showed that intranasal administration of NGF reduced the immobility time in forced swimming test (FST) and tail suspension test (TST) in mice. Likewise, intranasal NGF increased the sucrose intake and the locomotor activity in rats after unpredictable chronic mild stress (UCMS). Furthermore, intranasal NGF increased the levels of monoamine neurotransmitters (norepinephrine, dopamine) in the frontal cortex and hippocampus and affected the number of 5-bromodeoxyuridine (BrdU), c-fos and caspase-3 positive neurons in dentate gyrus of hippocampus in rats after UCMS. In summary, intranasal NGF had significant antidepressant effects on animal models of depression and this route of administration may provide a promising way to deliver NGF to brain in a therapeutic perspective.

Intranasally Administered Neuropeptide S (NPS) Exerts Anxiolytic Effects Following Internalization Into NPS Receptor-Expressing Neurons

“…This different onset of action probably originates from dissimilar pharmacokinetics and targeting efficiencies of intranasally vs ICVadministered drugs (Thorne et al, 1995(Thorne et al, , 2008Shi et al, 2010). As at 30 min after intranasal application of Cy3-NPS, a much weaker signal was observed than after ICV injection, it is possible that, although NPS does reach the brain rapidly after transnasal delivery, it may require additional time to reach its brain target cells in the full concentration required to produce behavioral effects.…”

Neurobiology of chronic mild stress: Parallels to major depression

“…Within the frontal cortical regions, several studies have revealed CMS-induced reductions in either 5-HT content itself (Vancassel et al, 2008; Sheikh et al, 2007; Li et al, 2003, 2009a; Yalcin et al, 2008; Yi et al, 2008; Xu et al, 2008; Rasheed et al, 2008; Vitale et al, 2009; Ahmad et al, 2010; Shi et al, 2010) or reductions in 5-HT turnover (Bekris et al, 2005). However, there have also been contradictory reports of CMS having no effect on 5-HT content or turnover in the frontal cortex (Dalla et al, 2005; Haidkind et al, 2003; Tannenbaum and Anisman, 2003; Johnson and Yamamoto, 2009, 2010; Dang et al, 2009b; Patterson et al, 2010; Laugeray et al, 2010).…”

“…Specifically, exposure to CMS reduces both 5-HT content (Vancassel et al, 2008; Sheikh et al, 2007; Li et al, 2003, 2009a; Yi et al, 2008; Xu et al, 2008; Rasheed et al, 2008; Ahmad et al, 2010; Shi et al, 2010; Kang et al, 2005; Chen et al, 2009; Zhang et al, 2004) and turnover [in females only; (Dalla et al, 2005)]. There is no effect of CMS on 5-HT transporter binding sites (Lopez et al, 1998) or protein levels (Cunningham et al, 2009), suggesting that these effects are likely due to changes in metabolism/catabolism rather than synaptic clearance.…”

Neuropeptide Y administration reverses tricyclic antidepressant treatment-resistant depression induced by ACTH in mice

“…Chronic administration of adrenocorticotropic hormone (ACTH) implemented by Kitamura et al (2002) is a method that provides some insight into the neurobiological mechanisms through which tricyclic antidepressant efficacy can be disrupted. In addition to the high levels of CRH and ACTH, serotonin (5-HT), toxic metabolites of kynurenine (KYN), their enzyme of activation (indoleamine 2,3-dioxygenase (IDO)) and proteins related to neurogenesis (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) have been postulated to play an important role in the pathogenesis of depression (Laske et al, 2010;Pandey et al, 2002;Shi et al, 2010).…”