summary: Octopamine is the major neurotransmitter responsible for the ‘fight or flight’ response in invertebrates and can communicate with mammalian brain cells to prevent cell death.
By introducing octopamine into astrocyte cultures, scientists found that it boosted the production of lactate, which promotes cell survival, a finding that could lead to future treatments for neurodegenerative diseases. I have.
The study also raises questions about the role of octopamine in the healthy brain and its effects on learning, memory and aging.
sauce: Northwestern University
Scientists at Northwestern Medicine have discovered how octopamine, a major “fight or flight” neurotransmitter in invertebrates, communicates with other cells in the mammalian brain to prevent cell death. Proceedings of the National Academy of Sciences.
Octopamine is still present in trace amounts in the mammalian brain, but its function has been replaced by epinephrine. Although long thought to be a leftover of mammalian evolution, octopamine’s role in the human brain has been poorly understood until now.
In the current study, researchers first sought to understand how astrocytes, which make up the majority of cells in the human central nervous system, contribute to brain dysfunction in neurodegenerative diseases. Scientists found that introducing specific levels of octopamine into astrocyte cultures from mouse cortex stimulated astrocytes to produce lactate, promoting cell survival.
“Our findings are significant because we discovered how this trace amine, octopamine, functions in the mammalian brain,” said Gabriela Caraveo Piso, PhD, assistant professor in the Ken and Ruth Davee Department of Neurology Division of Movement Disorders. I’m here. .
“Think of it like an SOS signal. Stressed neurons send this signal to astrocytes to send energy and lactate. It reads distress signals and allows them to start making energy that protects cells from dying from ATP starvation.Too much octopamine is like smoke in the way of SOS. .”
This finding may help inform future treatments for Alzheimer’s disease, Parkinson’s disease, and bipolar disorder, all of which are associated with dysregulation of octopamine levels in the brain.
“Lactic acid was long thought to be a waste product. We think this is important because it may affect other diseases in which octopamine levels are altered, such as.”
Going forward, Piso and collaborators hope to better understand how octopamine functions in the healthy brain.
“What we now want to know is, does this only occur in disease-like situations? Or does octopamine play a role under physiological conditions, such as learning and memory, where neurons also experience high energy demands?” will it fulfill?” said Carabeo Piso.
“Given that octopamine can harness astrocyte lactate metabolism, it is also of interest to understand the role of lactate metabolism in the brain in this context of memory and learning and aging.”
About this neuroscience research news
author: Olivia Dimmer
sauce: Northwestern University
contact: Olivia Dimmer – Northwestern University
image: Image adapted by Neuroscience News
Original research: open access.
“Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein” by Andrew Shum et al. PNAS
overview
Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein
Octopamine is a well-established invertebrate neurotransmitter involved in the fight-or-flight response. In mammals, its function has been replaced by epinephrine. Nevertheless, it is present in trace amounts and can modulate the release of monoamine neurotransmitters by as yet unidentified mechanisms.
Here, through an interdisciplinary approach utilizing in vitro and in vivo models of α-synucleinopathy, the conversion of toxic astrocytes to neuroprotective astrocytes in the cerebral cortex by promoting aerobic glycolysis. revealed an unprecedented role for octopamine in promoting
Physiological levels of neuron-derived octopamine act on astrocytes via the trace amine-related receptor 1–Orai1–Ca2+– Calcineurin-mediated signaling pathway for stimulating lactate secretion.
Uptake of lactate into neurons via the monocarboxylase transporter 2-calcineurin-dependent pathway increases ATP and prevents neurodegeneration. Pathological increases in octopamine caused by α-synuclein shut down lactate production in astrocytes and short-circuit metabolic transmission to neurons.
Our study provides a unique function of octopamine as a modulator of astrocyte metabolism and subsequent neuroprotection with effects on α-synucleinopathy.
