“Octopamine: The Neurotransmitter that Could Prevent Neurodegenerative Diseases”

summary: Octopamine, the main neurotransmitter responsible for the “fight or flight” response in invertebrates, can communicate with mammalian brain cells to prevent cell death.

By introducing octopamine into astrocyte cultures, scientists have found that it stimulates lactate production, which increases cell survival, and this discovery could lead to the future treatment of neurodegenerative diseases.

The study also raises questions about the role of octopamine in the healthy mind and its impact on learning, memory and aging.

source: Northwest University

Northwestern Medicine scientists have discovered how octopamine, a key “fight or flight” neurotransmitter in invertebrates, communicates with other cells in the mammalian brain to prevent cell death, according to a study published in the journal Prosiding National Academy of Sciences.

Although octopamine is still present in the mammalian brain in small quantities, its function has been replaced by epinephrine. Long considered an evolutionary remnant in mammals, octopamine’s role in the human brain was not previously well understood.

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. In astrocyte cultures from the rat cerebral cortex, scientists found that introduction of octopamine at certain levels triggers lactate production in astrocytes, which promotes cell survival.

says Gabriela Carafio Pesso, PhD, assistant professor in the Kane and Ruth Dave Department of Neurology, Division of Movement Disorders.

Think of it as a distress signal; stressed neurons send this signal to astrocytes to deliver energy to them, to deliver lactate. At the right levels, octopamine allows astrocytes to read these distress signals and start generating energy that protects cells from death. from ATP deficiency. If there’s too much octopamine, it’s like smoke blocking SOS. Astrocytes can’t read them.”

Carafio-Pizzo said the findings could help identify future treatments for Alzheimer’s disease, Parkinson’s disease and bipolar disorder, which are all linked to unregulated octopamine levels in the brain.

“Lactate has been seen as a waste product for a long time. But it’s not, it’s a very important fuel that nerve cells need to switch to a higher form of energy,” said Carafio Peso. “We think this is important because it can affect other diseases by altering Octopamine levels, including Alzheimer’s disease and psychiatric disorders.”

Going forward, Bezo and his collaborators hope to better understand how octopamine acts in a healthy brain.

“What we want to know now is: Does this only occur in disease-like conditions? Or does octopamine play a role in physiological conditions such as learning and memory, where neurons also experience high energy demands?” said Caravio-Pizzo.

“Given that octopamine can leverage lactate metabolism in astrocytes, we were also interested in understanding the role of lactate metabolism in the brain in the context of memory, learning and aging.”

About this research in Neuroscience News

author: Olivia Deamer
source: Northwest University
communication: Olivia Deamer – Northwest College
picture: Image from Neuroscience News

Original search: open access.
“Octopamine metabolically reprograms astrocytes to provide neuroprotection against α-synucleinBy Andrew Shum et al. PNAS

summary

Octopamine metabolically reprograms astrocytes to provide 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. However, it is present in small amounts and can modulate monoamine neurotransmitter release by a mechanism that has yet to be determined.

Here, through a multidisciplinary approach using in vitro and in vivo models of α-synucleinopathy, we have explored the unprecedented role of octopamine in driving the switch from excitotoxic to neuroprotective astrocytes in the cerebral cortex by promoting aerobic glycolysis.

Physiological levels of neuron-derived octopamine act on astrocytes via the amine-binding 1–Orai1-Ca receptor.²⁺Calcineurin-mediated signaling pathway to stimulate lactate secretion.

It enhances uptake of lactate into neurons through the monocarboxylate transporter 2 – the calcineurin-dependent ATP pathway and prevents neurodegeneration. The pathological increase in octopamine induced by α-synuclein stops lactate production in astrocytes and shortens the metabolic communication of neurons.

Our work provides for the unique function of octopamine as a modulator of astrocyte metabolism and subsequent neuroprotection with implications for alpha-synuclein disruption.