MK-677 and Brain Damage: What Is The link?

MK-677, or Ibutamoren, can mimic the hunger hormone Ghrelin and stimulate Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1) release. GH and IGF-1 are released from the pituitary gland and act on receptors throughout the brain. Therefore is there a link between MK-677 and brain damage? Does MK-677 cause brain damage or does MK-677 reverse brain damage? This blog will answer these questions.
Klara Hatinova

Klara Hatinova

Klara is postgraduate researcher in experimental psychology at the
University of Oxford.

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What is MK-677?

MK-677 is the popular name for the synthetic drug Ibutamoren. MK-677 mimics the effects of the peptide for weight loss ghrelin by acting on the growth hormone secretagogue-receptor type 1a (GHSR-1a). By activating GHSR-1a, MK-677 stimulates the release of Human Growth Factor (GH) from the anterior pituitary gland on the base of the brain [1].

MK-677 brain damage would imply that taking MK-677 would reduce cognitive function, such as memory or attention, or damage to physical brain structures.

To better understand whether MK-677 can cause or reverse brain damage, we must examine the impact of Ghrelin, GH and IGF-1 on brain damage.

What are the Effects of Ghrelin, the Biological MK-677 Analog, on the Brain?

Ghrelin, often referred to as the 'hunger hormone,' is a peptide hormone that regulates various brain functions. It affects the brain's metabolic activity in a wide range of areas [2].

Ghrelin positively affects brain damage, as it can enhance neuronal survival. It reduces apoptosis, alleviates inflammation and oxidative stress, and improves mitochondrial function [3]. Ghrelin also stimulates the proliferation, differentiation, and migration of neural stem/progenitor cells (NS/PCs) [3].

Ghrelin has been found to impact memory and cognitive functions. However, while it alters encoding-related brain activity, it does not necessarily enhance human memory formation [4]. In contrast, other studies have shown that ghrelin increases memory retention, suggesting that the peptide may influence processes in the hippocampus [5].

Lastly, ghrelin has been suggested as a potential therapeutic agent in neurodegenerative disorders. It has been shown to combat the degenerative process of Alzheimer's disease by eliciting a regenerative response to counteract neuronal death [6].

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What are the Effects of Growth Hormone on the Brain?

Human growth hormone (GH) has several beneficial effects on the brain, influencing cognitive function, memory, and brain structure. These have been reviewed in the prominent scientific journal Nature [7].

Growth Hormone for Learning and Memory

GH has been shown to improve cognitive function in both human and animal models.

By interacting with excitatory neurotransmitters and neuromodulators, such as glutamate and dopamine, GH can restore cognitive function following a stroke or traumatic brain injury, suggesting that MK-677 could reverse brain damage [7]. Outside the CNS, GH also improved spinal cord damage [8].

Preclinical studies have shown that GH increases density and functionality of GABAB receptors in the brain. GABAB is a critical receptor in learning and memory, which are cognitive functions frequently affected in brain damage. These were particularly prominent in the cingulate cortex, and basal ganglia structures [9].

Growth Hormone for Brain Regeneration

GH also appears to have a role in brain growth, development, and myelination, which has been studied in detail in animal and cell models. The brain damage protection of GH is likely linked to its interaction with IGF-1, which will be discussed in the following section. GH can protect against brain damage by increasing division of unspecialised cells, that can specialise into new neurons, oligodendrocytes, and blood vessels. This effect was most notable in the hippocampus's dentate gyrus, a critical memory area [10].

What are the Effects of Insulin-like Growth Factor 1 on the Brain?

Insulin-like growth factor 1 (IGF-1) plays a significant role in the brain, influencing various aspects of brain health and function. It can offer protection against harmful insults across many biological systems, including the brain [11]. This was demonstrated in a study where IGF-1 was partially depleted in a mouse model.

IGF-1 has a critical neuroprotective role. In a mouse model of ischemia, it can protect neurons in the cortex and subventricular zone, the storage region of neural progenitor cells that can become new neurons [12]. IGF-1 can also protect other regions of the brain against ischemic brain damage, such as the hippocampus [13]. Thus, IGF-1 is a critical therapy for stroke brain damage.

IGF-1 also plays a role in brain development and plasticity. It promotes the growth of neurons, dendrites and the formation of synapses, which are essential for forming and maintaining healthy neural networks [14]. Furthermore, IGF-1 and its active peptide (1-3)IGF1 enhance the expression of synaptic markers in neuronal circuits [15].

In brain injury, IGF-1 supplementation can improve cognitive function and mitophagy, a biological process that helps maintain cell health by removing damaged mitochondria [16]. It also has a role in modulating the brain's response to proinflammatory cytokines, which can have antidepressants effects, among other benefits on neurodegeneration [17].

Regarding cognitive function, IGF-1 has been linked to improved memory performance and synaptic transmission in the hippocampus [18]. However, it's important to note that the relationship between IGF-1 and cognitive function is complex and may depend on various factors, including the underlying pathology and context [19].

Summary: Does MK-677 Cause or Prevent Brain Damage?

To summarise – MK-677 is likely a powerful agent to reverse and prevent brain damage. Through its effects on mimicking ghrelin, increasing GH and IGF-1, MK-677 can improve synaptic plasticity, memory, cognitive function and support the growth of healthy neural networks. In this aspect, MK-677 could be a new class of study drug.

Despite the protection of MK-677 against brain damage, MK-677 is an illegal substance and is not yet an approved therapeutic agent for any of these conditions. There is also evidence linking MK 677 and cancer.

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Klara Hatinova

Klara Hatinova

Klara is a postgraduate researcher in experimental psychology at the University of Oxford. She has worked across a spectrum of hot topics in neuroscience, including her current project measuring reinforcement learning strategies in Parkinson’s disease. Previously, she studied the efficacy of psilocybin as a therapy for critical mental health conditions and examined molecular circadian rhythms of migraine disorders. She completed her undergraduate degree in Neuroscience at the University of Glasgow and participated in a year abroad at the University of California, where she worked on a clinical trial for spinal cord injury.