Related Experiment Videos
Abnormal expression of microtubule-associated protein 2 (MAP-2) in neocortex in Rett syndrome
W E Kaufmann1, S Naidu, S Budden
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract:
Immunocytochemical evaluations of the neocortex of three classical Rett syndrome (RS) individuals revealed a selective abnormality in the expression of microtubule-associated protein 2 (MAP-2). MAP-2 immunoreactivity (ir) was reduced throughout the neocortex of all three RS cases with a reversal of the normal pattern of more intense staining in deep cortical layers. This anomaly was selective for MAP-2 because nonphosphorylated neurofilament (SMI-32) labeling of deep pyramidal neurons and calbindin (CaBP)-stained GABAergic cells remained unchanged. Moreover, MAP-2 ir was virtually undetected in white matter while GABAergic and, particularly, peptidergic (neuropeptide Y: NPY) profiles were easily recognized. These results demonstrate a marked disruption of a major cytoskeletal component in neocortex in RS which seems to affect, predominantly, pyramidal projection and white matter neurons. MAP-2 expression appears early in neuronal maturation of the neocortex, particularly in the subplate region, the future superficial white matter, suggesting that these reported abnormalities in RS represent a developmental disturbance. Considering that MAP-2 expression is regulated by several neurotransmitter systems in adult cerebral cortex, particularly dopaminergic and cholinergic afferents that are deficient in RS, these neurochemical alterations could be related to this anomalous MAP-2 expression.
Insights
Rett syndrome (RS) neocortex shows reduced microtubule-associated protein 2 (MAP-2) expression, affecting pyramidal and white matter neurons. This disruption suggests a developmental disturbance linked to neurotransmitter deficiencies in RS.
Area of Science:
- Neuroscience
- Developmental Biology
- Cell Biology
Background:
- Rett syndrome (RS) is a neurodevelopmental disorder.
- Microtubule-associated protein 2 (MAP-2) is crucial for neuronal structure and function.
- Altered cytoskeletal components are implicated in neurodevelopmental disorders.
Observation:
- Immunocytochemical analysis of neocortex from three classical Rett syndrome individuals.
- Selective reduction in MAP-2 immunoreactivity (ir) observed across all cortical layers.
- Normal expression patterns of nonphosphorylated neurofilament (SMI-32) and calbindin (CaBP) were maintained.
Findings:
- A significant decrease in MAP-2 expression was detected in the neocortex of RS patients.
- MAP-2 ir was notably absent in white matter, contrasting with preserved GABAergic and NPY profiles.
- These findings indicate a selective disruption of a major cytoskeletal component in RS.
Implications:
- The observed MAP-2 abnormalities suggest a developmental disturbance during neocortical maturation in RS.
- Potential links between anomalous MAP-2 expression and neurotransmitter system deficiencies (dopaminergic, cholinergic) in RS are proposed.
- This research highlights MAP-2 as a potential biomarker and therapeutic target in Rett syndrome.