What is the Origin of Excitotoxicity?

The term originated in neuroscience and neuropharmacology following the discovery of the potent neurotoxic effects of glutamate and its analogs in the mid-20th century. Research subsequently identified the specific receptor subtypes, particularly the NMDA and AMPA receptors, responsible for mediating this excessive excitatory signaling.

What is the Mechanism of Excitotoxicity?

The core mechanism involves the persistent activation of ionotropic glutamate receptors, leading to the massive depolarization of the postsynaptic membrane and the subsequent, sustained opening of voltage-gated calcium channels. This overwhelming intracellular calcium load triggers a sequence of destructive events, including the activation of calcium-dependent proteases, lipases, and endonucleases, ultimately leading to mitochondrial dysfunction and necrotic or apoptotic cell death. Hormonal factors, such as sex steroids, can modulate the expression and function of these glutamate receptors, influencing neuronal vulnerability.

Excitotoxicity ∞ Area

Excitotoxicity

Meaning

Excitotoxicity is a pathological process where excessive or prolonged stimulation of neurons by excitatory neurotransmitters, primarily glutamate, leads to neuronal damage and eventual cell death. This overstimulation results in a cascade of detrimental intracellular events, including the uncontrolled influx of calcium ions, which overwhelms cellular homeostatic mechanisms. Excitotoxicity is a key mechanism implicated in acute neurological insults, such as stroke or trauma, and in the progression of various chronic neurodegenerative disorders.

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Excitotoxicity

Meaning

Origin

Mechanism

Can Lifestyle Adjustments Complement Hormonal Protocols for PMDD Neurobiological Support?

How Does Progesterone Influence Neurotransmitter Balance?

What Are the Neuroprotective Benefits of Melanocortin System Activation?

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