Infusion of growth hormone into the hippocampus induces molecular and behavioral responses in mice

Abstract

Growth hormone (GH) has been implicated in a variety of brain functions, including neural development, cognition, and neuroprotection. The biological effects of GH are known to rely on the binding of GH to the GH receptor (GHR), yet the resulting signals in the brain remain poorly understood. The present study investigated the effects of hippocampal infusions of recombinant GH and a GHR antagonist on the expression of immediate early genes (IEGs) and behavioral responses in mice. The infusions induced differential expression of Arc, Nr4a1, and Npas4 mRNAs among the IEGs. The infusions also elicited differential behavioral responses, such as varied levels of spontaneous locomotion, self-grooming, and frequency of access to the corner fields in the open-field test. Polynomial regression analyses and canonical discriminant analyses between gene expression and behavioral changes demonstrated that the expression level of Arc mRNA was strongly correlated with locomotor activity level (r = 0.71 and 0.92 on days 8 and 10, respectively) and that the correlation was completely discriminable between drugs (error rate = 0%). This analysis also revealed that a decrease in Npas4 mRNA was negatively correlated with the number of corner accesses (r = -0.63) and that this correlation was partially discriminable between drugs (error rate = 16.67%). Taken together, these results suggest that the GH-GHR complex modulates Arc and Npas4 signaling, which affects spontaneous locomotor and exploratory behaviors.

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

“…However, these positive effects of GH have been widely demonstrated in different experimental animal models [29,30,31,32,33]; even in old animals, in which the cognitive impairment of hippocampal-dependent functions, such as learning and memory, is associated with a decrease in the secretion of GH and IGF-I, as in our species [4,17,18,32]. …”

Npas4 Transcription Factor Expression Is Regulated by Calcium Signaling Pathways and Prevents Tacrolimus-induced Cytotoxicity in Pancreatic Beta Cells

“…Neuronal Npas4 mRNA expression had been linked previously to stimulation by growth factors (45,58), although this may not translate to changes at the protein level (29). Specifically, Ooe et al (45) have reported that Npas4 expression downstream of NGF stimulation was dependent on PI3K/Akt.…”

Neural growth hormone: regional regulation by estradiol and/or sex chromosome complement in male and female mice

“…In addition, GH deficiency has been linked with cognitive impairment [ 16 , 35 , 37 ], and previous research has shown that Gh expression increases in the rat hippocampus following repeated learning in response to eye-blink conditioning [ 38 ]. In mice, infusion of GH into the hippocampus changes expression of immediate early genes and induces spontaneous locomotion, grooming, and anxiety-like behavior [ 39 ]. Consistent with observations in rat, our data in mice show that Gh is expressed in the hippocampus in a hormone-dependent manner; this may be an important aspect of learning and memory mediation by Gh .…”