Kainic acid has aided neuroscience in advanced research and conceptualization of the molecular, neurochemical, and pharmacological mechanisms of underlying conditions like epilepsy and seizures. Over the decades, the kainic acid effect was not fully recognized. However, primitive researchers took note of the signs revealed after concurrent administration. Following further investigations into the brain tissue and a thorough study of its histoarchitectural regions, it was later discovered how the impact is made on areas of the brain and the degree of the impact . The hippocampus, the long-term memory processing and storage tool, is most susceptible to change in neurological dynamics after the administration of kainic acid. Kainic acid is currently a model in Neurotoxicological research projects . The aim of the article is to reveal research project outcomes at the histological and molecular level in the changes in the expression of the hippocampus following kainic acid administration.
Kainic acid (KA )is similar in function to glutamate, which displays powerful, long-acting excitatory and toxic chemistry on the nerve cells of the nervous system. In neuroscience research studies, KA serves as a useful model for studying damaged neurons and mimicking the actions of glutamate on the glutamate receptors in the brain . Glutamate is a neurotransmitter, a chemical messenger of the nervous system that transmits impulses from the terminal of a neuron through the synapse to the targeted neuron. KA originated from seaweeds in Japan in 1953. It was used as a traditional medication for several years without any observations of its potential side effects. Decades of experimental research studies revealed that kainic acid has a toxicological impact on the nervous system.
The receptors of KA are receptors of the glutamate neurotransmitter that mediate rapid excitatory neurochemistry. These receptors are located on the synaptic terminals of the designated neuron, the presynaptic and postsynaptic terminals. The rapid influx of sodium ions is regulated by the excitatory action of KA on occupied neurons, and in this case, KA is referred to as an excitant. These receptors (along with AMPA receptors) underlie the central nervous system, rapid synaptic transmission, and gate an ion channel regulating the influx of sodium ions . The receptors to which KA binds to are ionotropic receptors with subclasses. The receptor subclasses include alpha-amino-5-methyl-3-hydroxyisoxazolone-4-propionate (AMPA), N-methyl-D-aspartate receptors, metabotropic receptors, and kainate glutamate receptors. The sporadic rush of sodium ions that produces an excitatory signal in the postsynaptic terminal of the targeted neuron is triggered by the binding of glutamate to the kainate subclass of glutamate receptors. KA also rapidly produces excitatory effects when bonded with the kainate subclass of glutamate receptors .
Roles of the kainate receptors include synaptic signaling and plasticity. These effects may occur quickly. Agonists of kainate receptors include glutamic acid (glutamate), KA, Domoic acid, and 5-iodowillardiine. Antagonists of the kainate receptor include Ethanol, Kynurenic acid, Tezampanel, and Theanine.
Memory storage for the enhancement of cognitive processes and judgment is controlled by the hippocampus. The hippocampus is the region of the brain associated with memory functions and storage. It is deeply located in the temporal lobe of each cerebral cortex .
The hippocampus belongs to or is part of the limbic system that functions in motivation, emotion, learning, and memory processes .
Anatomy of the Hippocampus
The hippocampus is a structure situated along the axis of the medial segments of the temporal lobes, forming the medial wall of the lateral ventricular inferior horns. It is made up of three components:
Hippocampus proper (Cornu Ammonis)
Histology of the hippocampus is composed of many layers ranging in surface areas, which include:
An external molecular or plexiform layer
A striatum oriens layer
A pyramidal cell layer
A striatum radiatun layer
A stratum lacunosum molecular layer
Histological studies have shown that the hippocampus is divided into different regions called fields: CA1, CA2, CA3, and CA4. CA stands for Cornu Ammonis.
The first field, also called the CA1 field and the field of Sommer largely consists of the pyramidal cells closest to the Subicular cortex. CA2 and CA3 are located in between CA1 and the Subicular cortex. The conus ammonia IV (CA4) is formed by the cells of the hippocampal hilus .
Gliosis and Atrophy of Neurons
After several studies on the neurological effects of kainic acid on the hippocampus, it was revealed that there was a significant neuronal loss in the hippocampus. On the entire hippocampal formation, there is rapid and complete degeneration of neurons, followed by gliosis and atrophy. A decreased number of positive cells is observed in all areas of the hippocampus and in both blades of the dentate gyrus after administration of kainic acid . Massive degeneration is observed in CA1 and CA3 areas of the hippocampus and the hilus of the dentate gyrus. Cells affected include Microglia, Astrocytes, and most of the pyramidal cells. Shrinkage or morphological changes of these neurons are revealed after the administration of kainic acid .
Changes in Enzymatic Machinery of Neurons
Enzymes that catalyze the transmission of impulse chemically are also affected. The mechanisms of enzymatic activity change from the normal state and rate after the administration of kainic acid in the hippocampus. Studies have shown that there is a significant decrease in the activity of specific biomarkers. Biomarkers for GABAergic neurons, which include the glutamic acid decarboxylase, have been tested and proved in multiple instances. Additionally, a change is observed in the cholinergic and noradrenergic afferent neurons of the hippocampus. When kainic acid is induced, no significant alteration occurs in the activity of choline acetyltransferase, but an increase in tyrosine hydroxylase is observed .
Reversal of Calcium Loading
The accumulation of calcium, which has been revealed in several research studies, mostly occurs in the postsynaptic neurons of the hippocampus. Little or no changes in calcium loading were discovered immediately after administration of kainic acid. Many hours after administration, however, demonstrated the reversibility of calcium loading after the termination of seizure activity. It was also demonstrated that calcium accumulated in the soma of the pyramidal neurons and mitochondria dynamics of basal neurons of the CA1 and CA3 areas of the hippocampus. Astrocytes were also affected with significant ischemic reactions, limiting the rate of their functions in the hippocampus .
Kainic acid is referred to as an excitotoxic substance, and its administration induces seizures predisposing to neurodegeneration. Studies have shown that kainic acid vandalizes the third and fourth field of the conus ammonia of the hippocampus but occasionally spares the first field and dentates gyrus . Destruction of the neurons in these areas leads to a reduction in the efficacy of feedback on neurons, most commonly to the pyramidal cells. Studies have shown that 5 days after kainic acid administration, seizures were initiated in rats. Before that, neurons were damaged in and out of the hippocampal area of the brain. The seizures may have been convulsive or non-convulsive depending on the histoarchitecture of the hippocampus or an underlying condition like Parkinson’s, Alzheimer’s, or Huntington’s disease .
The ratio of the physiological and toxicological effects of kainic acid is drastically engulfed. The kainic acid research model has shown that it does not only affect the hippocampal area or limbic system of the brain. The striatum, thalamus, and other vital areas are also affected by the induction of this acidic substance .
Seaweed consumption has been terminated as kainic acid, which was initially thought to be a neurophysiological agent but has now been confirmed as a neurotoxicological agent. A recognized glutamate neurophysiological action is to aid the cognitive process of the brain, which can only happen when the glutamate neurotransmitter binds the appropriate receptor to elicit the designated action without any antagonism. Kainic acid excessively expresses itself in the hippocampus to cause harm to the microglia, reducing the immune response of the hippocampus. In addition to this, it slows down metabolism by affecting the astrocytes and reducing the potential of synaptic plasticity. Neuroscientists should collaborate with biochemists and nutritionists to further research studies on seafood products and their biochemical expressions on the brain.
Epilepsy: a seizure disorder characterized by the disturbance of neuronal activity in the brain
Histoarchitecture: the structure of biological tissue
Excitatory: related to promoting the generation of an electrical signal in a receiving neuron
Impulse: a message or signal transmitted from a sensory organ or tissue to the effector organ or tissue
Dendrites: branched extensions of a neuron that serve as the receptive role in a synapse
Synapse: a neuronal junction that is the site of transmission of an impulse from the terminal end of one neuron to the dendrites of another neuron
Receptors: biochemical structures made up of protein that are responsible for the reception of impulses and signals
Influx: the arrival, entry, or invasion of a substance
AMPA receptors: glutamate receptors that function in the integration of neuronal plasticity and synaptic transmission of impulses at the postsynaptic membrane
Plasticity: the adaptability of the brain to changes in the environment of its processing mechanisms
Agonist: a chemical substance that binds to a receptor and activates the receptor to produce a biological response
Antagonist: a chemical substance that inhibits the action of an agonist
Amygdala: a limbic structure in the brain that is often regarded as the emotional control center
Hypothalamus: a structure in the brain that is responsible for a variety of functions, such as regulating hormone levels, hunger, and satisfaction
Lateral ventricles: the largest ventricles (hollow spaces within the brain that contain cerebrospinal fluid) in the brain, situated bilaterally (one on the left side and one on the right)
Entorhinal cortex: a region of the brain that is located on the medial side of the temporal lobe and is responsible for memory, navigation, and the perception of time processing
Dentate gyrus: the hippocampal circuit that is thought to be responsible for the formation of new memories
Astrocytes: glial cells in the central nervous system that are responsible for blood-brain barrier permeability and the maintenance of extracellular homeostasis
Microglia: glial cells that serve as the immune defense mechanism of the central nervous system
Celestine Reuben is an Undergraduate of the Federal University of Technology, Akure, Ondo, Nigeria. Studying the course HUMAN ANATOMY. I look forward to studying the field of Neuroscience, Pharmacology, and Radiology, Mathematics and apply these professions in FORENSIC SCIENCE AND ENGINEERING