The Effect of Intra-Hippocampal Injection of Growth Hormone on Spatial Learning and Memory in Animal Model of Alzheimer’s Disease

Abstract

The aim of this study was to evaluate the effect of intra-hippocampal injection of Growth Hormone (GH) on impaired spatial cognition in rats with Alzheimer's Disease (AD). Growth hormone replacement therapy leading to improved cognition and well-being has mainly been carried in GH-deficient patients. Nevertheless, relatively only a few studies have investigated the function of GH in the brain. Aged Wistar male rats (350-400 g, 18-20 months old) were randomly divided into 6 groups (7 in each): Control (healthy aged); L; L + Veh; L + GH10; L + GH20 and L + GH40. Rats with AD-like cognitive deficiency was induced by injection of ibotenic acid into Nucleus Basalis of Meynert (NBM) bilaterally (5 microg 0.5 microL(-1), each side). A guide cannula was implanted in the right hippocampus under stereotaxic surgery for injection of human recombinant GH (10, 20 and 40 microg 2 microL(-1), during 5 min, twice daily, 9:00 am and 3:00 pm, for 7 days). All rats were trained in Morris water maze to evaluate the spatial learning and memory. Escape latency, traveled distance to find hidden platform and percent time spent in gaol qudrant did not differ between L and L + Veh groups, while latency and distance were reduced significantly. But percent time spent in gaol quadrant (without hidden platform) was increased significantly in NBM-lesioned rats treated with GH (L + GH groups) dose dependently to compare with vehicle treated group. These results suggest that intra-hippocampal injection of GH to aged rats with dementia type of AD (with NBM lesioned) could improve spatial cognition.

Candidate SNP Markers of Familial and Sporadic Alzheimer's Diseases Are Predicted by a Significant Change in the Affinity of TATA-Binding Protein for Human Gene Promoters

“…Our primary keyword search produced the article (Malek et al, 2009) on the somatotropin-based treatment of some complications of sporadic AD (Turnaev et al, 2016). In addition, our secondary keyword search yielded a lot of articles on the negative correlation between this disease and the human stature, the most interesting of which (in our opinion) states that stature maximization in both childhood and adolescence as the integral indicator of health can minimize (or even delay) dementia in the elderly (1892 cases) (Beeri et al, 2005) (Table S1).…”

Effect of intra-hippocampal injection of human recombinant growth hormone on synaptic plasticity in the nucleus basalis magnocellularis-lesioned aged rats

“…However, in this regard, more studies have been done on IGF-1, but synaptic functions of GH are independent of IGF-1, and the separate effects of GH still need to be evaluated 22 . Previous studies in our laboratory have shown that intrahippocampal and peripheral injection of GH or IGF-1 can attenuate spatial learning deficit in a dose-dependent manner in NBM-lesioned aged rats 15,23 . The purpose of this study was to assess the direct central actions of GH on electrophysiological properties of hippocampal neurons.…”

“…NBM lesioning: rats were anesthetized with an intraperitoneal injection of ketamine (100 mg.kg -1 body weight) and xylazine (10 mg.kg -1 body weight) 15 . The animals were placed in a stereotaxic frame, lesions were made by injecting ibotenic acid bilaterally (0.5 μg.0.1 μl -1 distillate water on each side for 5 min, Sigma-Aldrich Chemical Co., USA) into the NBM according to the rat brain atlas (AP; -1.3, L; ±2.3, V; -6.6) 24 .…”

“…It has recently been shown that age-related reductions in plasma GH, known as somatopause, is associated with increased incidence of cognitive impairment and AD, and can be compensated through GH treatment 10,11 . Various central effects of GH, such as cell genesis, neurogenesis 12 and angiogenesis 13 , suggest that GH administration may be effective in preventing the development or progression of AD 9,14,15 . Molecular mechanisms of improved cognitive functions after GH treatment are not known but may be due to the direct impact of the hormone on the brain.…”

NMDA Receptor-Mediated Neuroprotective Effect of theScutellaria baicalensisGeorgi Extract on the Excitotoxic Neuronal Cell Death in Primary Rat Cortical Cell Cultures

“…Baicalin has also been reported to preserve heat shock protein 70 (HSP70), with the latter being known to exert protective effects in neurons [25–27]. S. baicalensis as such has been shown to exhibit memory enhancing properties against ibotenic acid (toxin), chronic lipopolysaccharide infusion, gamma-irradiation, beta amyloid proteins, ischemia, and so forth [28–31]. Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescence mice [32].…”