What you’re about to read is wild. Cold exposure has been shown to have protective effects against traumatic brain injuries and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Nothing excites us more than this emerging area of research, and its potential impact.
Most of us have had moments where we feel like our brain’s not quite functioning how it should – brain fog, stress, and poor sleep are common culprits. But there is also a global concern for dementia and neurodegenerative diseases, as the rates continue to rise. There are currently no cures or clear practices for prevention, but research involving cold exposure has highlighted a key protein that could be targeted to prevent and slow progression of the diseases, and approaches that could be applied more generally to sustain better brain function.
Cold Water Therapy, Neurogenesis, and RBM3
Neurogenesis is the process by which nervous system cells, known as neurons, are produced by neural stem cells. Until recently, many scientists believed that the adult central nervous system, including the brain, was incapable of regenerating. But in the 1990s, stem cells were discovered in parts of the adult brain and adult neurogenesis is now accepted to be a normal process that occurs in the healthy brain.
When you’re exposed to the cold, the body releases cold shock proteins known as RNA binding motif 3 (RBM3), which are directly linked to regeneration of synapses in the human brain. Synapses are gaps between neurons through which our neurons communicate, and are responsible for normal brain function and how we form memories. This effectively means that cold water therapy could play a role in decreasing the degeneration of our neurons, and therefore the prevention of neurodegenerative diseases, because it promotes the growth and development of nervous tissue and neurogenesis.
Synapses can get damaged and even disappear, but luckily for us, RBM3 reacts with the part of our neurons that utilises these synapses and boosts their productivity. RBM3 is a specific protein found in your brain, heart, liver, and skeletal muscle. The more RBM3 that is present in our brains, the better these cold shock proteins are able to stimulate damaged or degenerated synapses. RBM3 has been shown to not only repair and recreate synapses, but also regenerate neurons, preventing cognitive decline.
The specific ‘cold shock chemicals’ that trigger the process were discovered by the Cambridge dementia team in 2015: they cooled a control group of mice, and mice with Alzheimer’s disease and prion disease (another neurodegenerative disease) to the point where they became hypothermic, which means their body temperature fell below 35oc. When the mice were warmed back up, they found that the control mice could regenerate their synapses, but the others could not. They also discovered that levels of RBM3 soared in the control mice, but not in the others, suggesting that RBM3 could be the key to formation of synaptic connections.
We now know that the brain has the ability to create new pathways and modify its connections or rewire itself, referred to as neuroplasticity. In mouse models of degenerative diseases, RBM3 was found to mediate structural plasticity and protective effects of cooling against neuron loss, suggesting cold exposure as a potential protective therapy. This reflects the effects in hibernating mammals, where cooling induces loss of synaptic contacts, which are then reformed on rewarming. In one study of Alzheimer’s in mice, it was also reported that not only does RBM3 switch on in the mouse hippocampus in response to hypothermia, it also protects cultured neurons from cell death when the temperature drops. This protective effect for both neurons and synapses has been demonstrated in multiple animal studies, including those which have demonstrated how its effects can be seen in the embryonic brain during pregnancy and how cold water swimming can improve cognitive deficits caused by experimental traumatic brain injury.
Human studies have also backed up the neuroprotective effects of RBM3 induced by cold exposure, with positive effects seen in cognitive functions, particularly in paradigms when circulating cortisol does not reach very high concentrations. The volume of research compounds the evidence of the protein’s significance for preventing neurodegeneration, and the role of cold exposure in its proliferation.
Norepinephrine and neurogenesis
Exposure to the cold has been proven to significantly increase norepinephrine levels, as high as 500%. Norepinephrine is a hormone and neurotransmitter which is responsible for the increased vigilance, focus, attention and mood that you get after you plunge into an ice bath or dip in the winter sea. It’s also one of the catecholamines, along with adrenaline and dopamine, and it’s produced by dopamine β-hydroxylase, which is released either as a hormone from the adrenal medulla into the blood or as a neurotransmitter in the brain.
Studies have shown that norepinephrine enables synaptic plasticity, and directly activates self-renewing and multipotent neural precursors, including stem cells, from the hippocampus of adult mice. It’s also a neuromodulator that regulates the activity of neuronal and non-neuronal cells in multiple ways. Norepinephrine participates in the rapid modulation of cortical circuits and cellular energy metabolism, and on a slower time scale, in neuroplasticity and inflammation.
To better understand the role of norepinephrine in memory, a ‘cold pressor stress’ is often used in research, usually by immersing a hand into ice-cold water. It’s known to be associated with substantial activation of the autonomic nervous system (the primary system governing our ‘fight-or-flight’ response), as well as mild to moderate activation of the hypothalamic pituitary adrenocortical (HPA) axis, which also plays an important role in our response to stress. It’s also associated with an enhancing effect on learning performance, with indications of a possible involvement in working memory. This is bolstered by studies on drugs that are capable of modulating emotional memory, such as GABAergic agonists and antagonists, that suggest they may do so by controlling the level of norepinephrine in the amygdala.
Dopamine and Neurogenesis
Dopamine plays a big part in what makes us human, helps us strive and makes us better learners. It’s a neurotransmitter which plays an important role in our executive function, motor control, motivation, arousal, reinforcement and reward. It does this through signalling cascades to dopaminergic receptors at projections found in the substantia nigra, ventral tegmental area and arcuate nucleus of the hypothalamus of the human brain. Dopamine disorders can often bring with them experiences of decline in the key neurocognitive functions that dopamine serves.
Adult hippocampal neurogenesis is severely impaired in neurodegenerative diseases, in particular Parkinson’s disease, which is the second most common neurodegenerative disorder. A now well-established hallmark in Parkinson’s disease is the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) with consecutive reduction of dopaminergic projections to the dentate gyrus (DG) and the striatum. Further study has found evidence that dopamine regulates adult neurogenesis, and may play a role in hippocampal neurogenesis, which would support the theory that it is critical in the progression and prevention of neurodegenerative diseases.
Along with the radical increase in norepinephrine during cold therapy, short periods of mild hypothermia also activate a release of dopamine in your brain. This, paired with soaring levels of norepinephrine, explain why you can’t help but smile and feel incredible after you’ve plunged into a cold bath. It’s also what makes cold water therapy such a promising treatment pathway for diseases like Alzheimer’s and Parkinson’s.
Wrapping it up
The bottom line? Practising good habits for our brains now is an investment in a healthier, longer future for ourselves, which means more quality time to achieve our goals and spend time with loved ones. The collective of elite athletes, tech entrepreneurs, mental health advocates and medics behind Monk all have personal experience of post-ice-bath mental clarity, and believe in its power to preserve and enhance our brain function.
Please note: educational information is not the same as medical or psychological advice. This blog post is reviewing published scientific evidence, and all information on this website is presented for educational and informative purposes only. It is not intended to replace professional, medical, or psychological guidance in any capacity.