Cerebellum, early structuring

Dystonia due to identifiable structural or biochemical abnormalities ( secondary dystonia) often occurs weeks or months after strokes or other focal lesions, which commonly involve the basal ganglia, but may also involve the thalamus or cerebellum. Dystonia is also seen in children with cerebral palsy and in patients with abnormalities of dopaminergic transmission. For instance, dystonia may develop in the context of Parkinson s disease, either as an early parkinsonian sign, or in response to dopaminergic drugs. A particularly interesting inherited disease results in a combination of dystonia and parkinsonian features at a young age, which responds dramatically to treatment with low-dose levodopa ( dopamine-responsive dystonia ). 

The determination of fhe embryonic "critical period of development" for the brain structures involved in learning and memory processes in mice is based on the original work by Rodier (1976). This study identified fhe embryonic time frames for peak neurogenesis and neuroepithelial proliferation for cerebral corfex, hippocampus, septum, amygdala, corpus striatum, thalamus, hypothalamus, cerebellum, and olfactory bulb as the period from embryonic day E14 fhrough E17. Rodier documented almost 40 years ago that the specific time of the central nervous system (CNS) insult is an important factor in subsequent effects on both anatomy and behavior. Therefore, this early work established what we refer to as the embryonic "critical period of development." The report suggested that the behavioral effects of toxicants such as benzo(a)pyrene (B(a)P) are similar in both rats and mice. This study was one of the first to demonstrate that mice could be used successfully as subjects in a variety of behavioral evaluation experiments. 

Chronic low-level lead exposure has been demonstrated to inhibit neural cell acquisition and impair early postnatal structuring of the central nervous system. Lead was demonstrated to have an anti-mitotic action both in vitro and in vivo, although the latter was confined to the cerebellum at blood lead threshold values of 30-40 jUg/dl. Low-level lead exposure more potently affected in vivo cell positioning and fibre outgrowth, as judged by the impaired developmental desialylation of the D2-CAM/N-CAM protein, and these effects were seen at blood lead threshold values of 20-30 jUg/dl. This inhibition of normal D2-CAM/N-CAM desialylation is attributed to improper guidance of neuronal cells and their fibres, as lead is demonstrated to specifically induce precocious differentiation of the glial cells. 

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