The Involvement of Insulin-Like Growth Factor 1 and Nerve Growth Factor in Alzheimer’s Disease-Like Pathology and Survival Role of the Mix of Embryonic Proteoglycans: Electrophysiological Fingerprint, Structural Changes and Regulatory Effects on Neurotrophins

Abstract

Alzheimer’s disease (AD)-associated neurodegeneration is triggered by different fragments of amyloid beta (Aβ). Among them, Aβ (25-35) fragment plays a critical role in the development of neurodegeneration—it reduces synaptic integrity by disruption of excitatory/inhibitory ratio across networks and alters the growth factors synthesis. Thus, in this study, we aimed to identify the involvement of neurotrophic factors—the insulin-like growth factor 1 (IGF-1) and nerve growth factor (NGF)—of AD-like neurodegeneration induced by Aβ (25-35). Taking into account our previous findings on the neuroprotective effects of the mix of proteoglycans of embryonic genesis (PEG), it was suggested to test its regulatory effect on IGF-1 and NGF levels. To evaluate the progress of neurodegeneration, in vivo electrophysiological investigation of synaptic activity disruption of the entorhinal cortex–hippocampus circuit at AD was performed and the potential recovery effects of PEG with relative structural changes were provided. To reveal the direct effects of PEG on brain functional activity, the electrophysiological pattern of the single cells from nucleus supraopticus, sensomotor cortex and hippocampus after acute injection of PEG was examined. Our results demonstrated that after i.c.v. injection of Aβ (25-35), the level of NGF decreased in cerebral cortex and hypothalamus, and, in contrast, increased in hippocampus, prompting its multidirectional role in case of brain damage. The concentration of IGF-1 significantly increased in all investigated brain structures. The administration of PEG balanced the growth factor levels accompanied by substantial restoration of neural tissue architecture and synaptic activity. Acute injection of PEG activated the hypothalamic nucleus supraopticus and hippocampal neurons. IGF-1 and NGF levels were found to be elevated in animals receiving PEG in an absence of amyloid exposure. We suggest that IGF-1 and NGF play a critical role in the development of AD. At the same time, it becomes clear that the neuroprotective effects of PEG are likely mediated via the regulation of neurotrophins.

Identification of IGF-1 Effects on White Adipose Tissue and Hippocampus in Alzheimer’s Disease Mice via Transcriptomic and Cellular Analysis

“…Several studies have shown that IGF-1 boosts hippocampal neurogenesis [ 106 ], restores spatial memory [ 48 ], and improves depressive-like behaviors through the regulation of serotonin [ 107 ]. Numerous studies have demonstrated that the administration of IGF-1 lessened brain atrophy [ 32 ], brain insulin resistance [ 108 ], apolipoprotein E-related neuropathology [ 109 ], and neurotransmitter secretion [ 110 ]. Other studies have mentioned that IGF-1 improved the long-term survival of hippocampal neurons [ 111 ] and spine maturation [ 112 ].…”

Effects of β-amyloid (1-42) Administration on the Main Neurogenic Niches of the Adult Brain: Amyloid-Induced Neurodegeneration Influences Neurogenesis

“…Our previous experiments revealed ambiguous shifts in the levels of nerve growth factor (NGF) and insulin-like growth factor (IGF) in brain structures; Aβ (25-35) induced an increase in IGF-1 levels in the hippocampus and cerebral cortex. Although NGF levels slightly increased in the hippocampus, these levels decreased in the cerebral cortex, indicating that sufficient concentrations of growth factors are a prerequisite for neural maturation [ 28 , 29 ]. The ratio of Bax-/Bcl-xL-positive cells increased by 50% in the SVZ and decreased 2.5-fold in the olfactory bulb, indicating the activation of the anti-apoptotic cascade.…”