Methylazoxymethanol acetate, MAM, is a neurotoxin which reduces DNA synthesis used in making

animal models A model organism (often shortened to model) 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 working ...

of neurological diseases including

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

and

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrica ...

. MAM is found in

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

seeds, and causes zamia staggers. It selectively targets

neuroblasts In vertebrates, a neuroblast or primitive nerve cell is a postmitotic cell that does not divide further, and which will develop into a neuron after a migration phase. In invertebrates such as ''Drosophila,'' neuroblasts are neural progenitor cells ...

in the

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

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

MAM animal models

Schizophrenia

In rat models, the specific effect of MAM on neural development depends on the

gestational age In obstetrics, gestational age is a measure of the age of a pregnancy which is 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. Su ...

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 (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

and the

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...

. 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 adminitred 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 An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

caused by flurothyl. 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