Aspects of Growth Hormone and Insulin-Like Growth Factor-I Related to Neuroprotection, Regeneration, and Functional Plasticity in the Adult Brain

Abstract

Apart from regulating somatic growth and metabolic processes, accumulating evidence suggests that the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is involved in the regulation of brain growth, development, and myelination. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are attributable to circulating IGF-I, while others may be due to IGF-I produced locally within the brain. Some of the shared effects in common to GH and IGF-I may also be explained by cross-talk between the GH and IGF-I transduction pathways, as indicated by recent data from other cell systems. Otherwise, it also seems that GH may act directly without involving IGF-I (either circulating or locally). Plasticity in the central nervous system (CNS) may be viewed as changes in the functional interplay between the major cell types, neurons, astrocytes, and oligodendrocytes. GH and IGF-I affect all three of these cell types in several ways. Apart from the neuroprotective effects of GH and IGF-I posited in different experimental models of CNS injury, IGF-I has been found to increase progenitor cell proliferation and new neurons, oligodendrocytes, and blood vessels in the dentate gyrus of the hippocampus. It appears that the MAPK signaling pathway is required for IGF-I—stimulated proliferation in vitro, whereas the PI3K/Akt or MAPK/Erk signaling pathway appears to mediate antiapoptotic effects. The increase of IGF-I on endothelial cell phenotype may explain the increase in cerebral arteriole density observed after GH treatment. The functional role of GH and IGF-I in the adult brain will be reviewed with reference to neurotransmitters, glucose metabolism, cerebral blood flow, gap junctional communication, dendritic arborization, exercise, enriched environment, depression, learning, memory, and aging.Briefly, these findings suggest that IGF-I functions as a putative regenerative agent in the adult CNS. Hitherto less studied regarding in these aspects, GH may have similar effects, especially as it is the main regulator of IGF-I in vivo. Some of the positive cognitive features of GH treatment are likely attributable to the mechanisms reviewed here.

Linking brains and brawn: exercise and the evolution of human neurobiology

“…For example, infusion of IGF-1 in the periphery leads to increased hippocampal neurogenesis [45], while hippocampal gene transfer of VEGF also enhances neurogenesis [46]. The role of VEGF and IGF-1 in neurogenesis was confirmed in a set of experiments showing that blocking peripheral VEGF and IGF-1 significantly inhibited APA-induced neurogenesis [4,7].…”

“…Research in both humans and animal models supports a strong role for neurotrophins and growth factors in brain development. Experimental work in rodents has shown that deficiencies in neurotrophins and growth factors during development in utero and post-natally lead to smaller overall adult brain sizes [45,[58][59][60], whereas overexpression of IGF-1 leads to significantly larger brain sizes at adulthood [61]. For example, in mice with homozygous inactivation of VEGF, brain size is significantly smaller than controls [62].…”

Traumatic Brain Injury Causes Long-Term Reduction in Serum Growth Hormone and Persistent Astrocytosis in the Cortico-Hypothalamo-Pituitary Axis of Adult Male Rats

“…These studies and reviews provide support for the role of GH=IGF-1 in cognitive function in adult-onset GH deficiency=aging. Given the apparent role of GH and IGF-1 in neuronal plasticity (Aberg et al, 2006), memory, and cognitive performance (Deijen et al, 1996(Deijen et al, , 1998Sonntag et al, 2005), it is likely that a decline in serum GH levels post-TBI may contribute to long-term deficits in memory functions and neuronal=cellular loss in the brain, which can be exacerbated and persistent long after traumatic injuries to the cerebral Cx.…”

“…Also, GH and IGF-1 play a role in myelin formation (Carson et al, 1993), neuronal plasticity (Aberg et al, 2006), and vascular tone (Sonntag et al, 1997), factors that are essential for brain repair after an injury=trauma. Therefore, in this study we looked at the long-term effects of TBI on the serum GH profile and inflammatory markers in the HP axis at 2 months post-injury, since persistence and progression of inflammatory and atrophic changes previously reported (Bramlett et al, 1997;Smith et al, 1997;Pierce et al, 1998;Holmin and Mathiesen, 1999) were evident one month post-injury (Smith et al, 1997;Pierce et al, 1998).…”

Impoverished environment, cognition, aging and dementia

“…Physical activity is part of an enriched environment, together with socialization (Studenski et al , 2006 ). It is known that an enriched environment induces a variety of neurophysiological changes, e.g., neurogenesis (Aberg et al , 2006 ). Living in an enriched environment could also improve cognition, i.e., learning and memory (Winocur , 1998 ;Williams and Kemper , 2010 ).…”