Brain sites of movement disorder: Genetic and environmental agents in neurodevelopmental perturbations

Abstract

In assessing and assimilating the neurodevelopmental basis of the so-called movement disorders it is probably useful to establish certain concepts that will modulate both the variation and selection of affliction, mechanisms-processes and diversity of disease states. Both genetic, developmental and degenerative aberrations are to be encompassed within such an approach, as well as all deviations from the necessary components of behaviour that are generally understood to incorporate "normal" functioning. In the present treatise, both conditions of hyperactivity/hypoactivity, akinesia and bradykinesia together with a constellation of other symptoms and syndromes are considered in conjunction with the neuropharmacological and brain morphological alterations that may or may not accompany them, e.g. following neonatal denervation. As a case in point, the neuroanatomical and neurochemical points of interaction in Attention Deficit and Hyperactivity disorder (ADHD) are examined with reference to both the perinatal metallic and organic environment and genetic backgrounds. The role of apoptosis, as opposed to necrosis, in cell death during brain development necessitates careful considerations of the current explosion of evidence for brain nerve growth factors, neurotrophins and cytokines, and the processes regulating their appearance, release and fate. Some of these processes may possess putative inherited characteristics, like alpha-synuclein, others may to greater or lesser extents be endogenous or semi-endogenous (in food), like the tetrahydroisoquinolines, others exogenous until inhaled or injested through environmental accident, like heavy metals, e.g. mercury. Another central concept of neurodevelopment is cellular plasticity, thereby underlining the essential involvement of glutamate systems and N-methyl-D-aspartate receptor configurations. Finally, an essential assimilation of brain development in disease must delineate the relative merits of inherited as opposed to environmental risks not only for the commonly-regarded movement disorders, like Parkinson's disease, Huntington's disease and epilepsy, but also for afflictions bearing strong elements of psychosocial tragedy, like ADHD, autism and Savantism.

A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

“…These findings resemble the idiosyncratic bouts of repetitive behaviors noted in autism. Autism has been grouped with the movement disorders [109] and the contribution of seizures to these behaviors may be underappreciated [3] .…”

Neurobehavioural deficits associated with apoptotic neurodegeneration and vulnerability for ADHD

“…The pathophysiology of the disorder remains unresolved, with a complex interaction of genetic, environmental and neurophysiological factors (cf. Rapport et al, 2000;Palomo et al, 2003). The genetic factor contributing to ADHD is substantial (e.g., Fisher et al, 2002;Smalley et al, 2002), reflecting associations with siblings , fathers (Frick et al, 1995) and mothers (Schacher and Wachsmuth, 1990;Faraone et al, 1998;.…”

“…Although the issue of animal models useful to a better understanding of ADHD is well-documented (cf. Davids et al, 2003;Palomo et al, 2003;Panksepp et al, 2003), the present study will present an alternative conceptualization of the putative neurodevelopmental 'accidents' implicated in the disorder, i.e., those involving the role of glutamate in development of brain systems.…”

Effects of Maternal Stress during Different Periods of Pregnancy on the Early Neurobehavioral Response of Rats

“…Following the maturation of certain neural reflexes and motor coordination may give us an insight into the neurodevelopment of prenatally stressed animals. It has been shown that reflex ontogeny in rodents is influenced by several factors such as undernutrition, maternal care, toxic agents, environmental enrichment, genetic background [22][23][24][25][26][27][28][29][30]. We have previously described that perinatal hypoxic and toxic injuries remarkably delay the neurobehavioral development but 3-hr-long maternal separation induces only slight changes [31][32][33][34].…”