Methylazoxymethanol acetate, MAM, is a

neurotoxin Neurotoxins are toxins that are destructive to nervous tissue, nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insult (medical), insultsSpencer 2000 that can adversely affect function ...

which reduces DNA synthesis used in making

animal models A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Mod ...

of neurological diseases including

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

and

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

. MAM is found in

cycad Cycads are seed plants that typically have a stout and woody (ligneous) trunk (botany), trunk with a crown (botany), crown of large, hard, stiff, evergreen and (usually) pinnate leaves. The species are dioecious, that is, individual plants o ...

seeds, and causes zamia staggers. It selectively targets neuroblasts in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. In rats, administration of MAM affects structures in the brain which are developing most quickly. It is an

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

methylazoxymethanol Methylazoxymethanol, MAM, is a carcinogen which reduces DNA synthesis. Its derivatives include methylazoxymethanol acetate and cycasin, which they are found in cycad Cycads are seed plants that typically have a stout and woody (ligneous) ...

MAM animal models

Schizophrenia

In rat models, the specific effect of MAM on

neural development The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field ...

depends on the

gestational age In obstetrics, gestational age is a measure of the age of a pregnancy taken from the beginning of the woman's last menstrual period (LMP), or the corresponding age of the gestation as estimated by a more accurate method, if available. Such metho ...

of the subject. At the seventeenth gestational day (GD17), administration of MAM produces behavioral and histopathological patterns found in schizophrenia. The molecular mechanism behind this model is not fully known. Methylazoxymethanol acetate administered at GD17 reduces the thickness of the

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

and the

thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...

. The locomotor effects of amphetamines and the spontaneous firing rate of dopaminergic neurons in the

ventral tegmental area The ventral tegmental area (VTA) (tegmentum is Latin for ''covering''), also known as the ventral tegmental area of Tsai, or simply ventral tegmentum, is a group of neurons located close to the midline on the floor of the midbrain. The VTA is th ...

are increased. In alternating maze tests, GD17 MAM rats quickly learned the first rule, but took longer to accommodate to alterations to the rule; this is thought to indicate deficits in working spatial memory, which is also impaired in schizophrenia. Another study found that mice whom methylazoxy-methanol acetate was administered on 16th gestational day, but not those whom it was administered on GD17 showed decreased parvalbumin expression in hippocampus and prefrontal cortex, and schizophrenia-like characteristics. Mice whom MAM was administered on GD16 also exhibited reduced size of hippocampus and thinning of the prefrontal cortex. PFC-dependent cognitive deficits were shown only in male MAM-treated mice.

Epilepsy

Exposure to MAM before birth increases susceptibility to epileptic

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

caused by

flurothyl Flurothyl (Indoklon) (IUPAC names: 1,1,1-trifluoro-2-(2,2,2-trifluoroethoxy)ethane or bis(2,2,2-trifluoroethyl) ether) is a volatile liquid drug from the halogenated ether family, related to inhaled anaesthetic agents such as diethyl ether, bu ...

. Prenatal MAM exposure in rats results in a model of brain malformation. In some MAM animals, video-EEG monitoring has documented the presence of spontaneous electrographic seizure activity In some epilepsy rat models, MAM is administered at the fifteenth gestational day. Previous studies have found impaired cognitive function in GD15 MAM rats, and a reduced seizure threshold. At the cellular level, dysplastic hippocampal neurons in the MAM model were shown to have reduced potassium current function and expression for the Kv4.2 channel subunit These findings may contribute to the spontaneous seizures and reduced seizure thresholds seen in this model.

References

{{Reflist, colwidth=33em Acetate esters IARC Group 2B carcinogens Azo compounds Azoxy compounds Natural products