title: Parkinson's disease: acquired frailty of archaic neural networks?
abstract: In Parkinson's disease (PD) many motor and non-motor symptoms are difficult to explain in terms of a purely ascending degeneration process as described by Braak. This essay proposes phylogenetic considerations for consolidating the multidimensional elements of PD. Subtle clinical analysis paired with ethological comparisons as well as patho-anatomical data suggests that disrupted automatic gait control, olfactory deficits, selected visual deficits, impaired emotional face recognition, and REM sleep behavior disorder could be due to dysfunction of phylogenetically ancient networks. Neuroanatomical and behavioral findings lead to a reconsideration of the basal ganglia, to be viewed as the nuclear core of a widely distributed neural network that arborizes throughout the primordial core of the neuraxis, including the brainstem. Fragility of the resulting multiple, closed, ancillary loops that link brainstem and forebrain components of the basal ganglia may be a nodal point, pivotal to the pathogenesis of PD. Other primitive neural networks, such as those located at cardiac or gastro-intestinal levels, may share the same vulnerability. Such a network-based hypothesis overrides the need of a fixed temporal ordering of symptoms based on putative caudal-cephalic propagation patterns of pathological lesions. It also creates testable, secondary hypotheses such as differential gene expression in different neural networks, potential early epigenetic influences, concepts of "overuse" or maladaptation of primitive networks to the constraints of adult life, and system frailty due to irreparable mitochondrial "exhaustion" in highly energy consuming postmitotic cells.
authors: Department of Neurosciences, Centre Hospitalier de Luxembourg, Luxembourg-City, Luxembourg. diederdn@pt.lu
authors: Nico J
authors: NJ
authors: Diederich
authors: André
authors: A
authors: Parent
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000473:pathology; D005075:Biological Evolution; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000473:pathology; D006801:Humans; D008959:Models, Neurological; D009415:Nerve Net / Q000473:pathology*; D009417:Nerve Tissue / Q000637:transplantation; D000857:Olfaction Disorders / Q000209:etiology / Q000523:psychology; D010300:Parkinson Disease / Q000473:pathology* / Q000628:therapy; D010802:Phylogeny; D014786:Vision Disorders / Q000209:etiology / Q000473:pathology