Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer's disease. III. The basal forebrain compared with other subcortical areas

Abstract

The distribution of the reticular neuronal type in the human brain and its involvement in both degeneration and dendritic reorganisation under the conditions of ageing, Korsakoff's disease (KD), Alzheimer's disease (AD), and Parkinson's disease (PD) was comparatively investigated after Golgi impregnation. Reticular neurones are distributed throughout different areas along the brain axis. The cholinergic basal forebrain nuclei, i.e., the basal nucleus of Meynert, the nucleus of the diagonal band, and the medial septal nucleus form the most rostral part of this network of "open nuclei," which is collectively referred to as the "reticular core." Reticular neurones of the following areas were quantitatively investigated by a computer-based three-dimensional analysis: caudate nucleus, globus pallidus, medial septal nucleus, nucleus of the vertical limb of the diagonal band, basal nucleus, medial amygdaloid nucleus, reticular thalamic nucleus, lateral hypothalamic area, subthalamic nucleus, substantia nigra, locus coeruleus, pedunculopontine tegmental nucleus, and raphe magnus nucleus. There are three major findings. First, neurones that were found to be susceptible to degeneration in AD were largely part of the same neuronal populations prone to degeneration during ageing, in KD and PD. Thus, areas could be classified according to their overall degree of vulnerability under the present degenerative conditions as being highly vulnerable (basal forebrain nuclei, caudate nucleus, locus coeruleus), moderately vulnerable (medial amygdaloid nucleus, raphe magnus nucleus, lateral hypothalamic area, substantia nigra, pedunculopontine tegmental nucleus), or marginally vulnerable (globus pallidus, subthalamic nucleus, reticular thalamic nucleus). Second, neuronal populations that are particularly vulnerable to degenerative changes show a high degree of structural plasticity. Third, the degree of this dendritic plasticity is inversely related to the complexity of dendritic arborisation of the neurone. It is concluded that the sparsely ramified reticular type of neurone forms a pool of pluripotent neurones that have retained their plastic capacity throughout life, which makes them vulnerable to a variety of perturbations.

Plastic Neuronal Remodeling Is Impaired in Patients with Alzheimer’s Disease Carrying Apolipoprotein ε4 Allele

“…The overall extent of degeneration and the gradual variation of cell loss between different areas are also in agreement with previous reports (Zweig et al, 1988;ChanPalay et al, 1992;Arendt et al, 1995c).…”

“…These findings implicate that patients with apoE ⑀4 alleles might reach more advanced stages of the disease at a younger age than patients without ⑀4. Previous studies have indicated that younger AD patients show a more severe degeneration (Bird et al, 1983;Rossor et al, 1984;Perry et al, 1992;Arendt et al, 1995b;Soininen et al, 1995) and a more intense plastic response of subcortical neurons (Arendt et al, 1995c) than older patients. Comparative studies on carriers and noncarriers of the ⑀4 allele might, therefore, be biased by agerelated effects.…”

Fine structure and synaptology of the nitrergic neurons in medial septum of the rat brain

“…The focus of research on cholinergic neurons within this complex aims to understand their role in etiology of certain dementias [8,22]. The septohippocampal pathway is important for learning and memory-related behaviors, and degeneration of cholinergic MS/DB neurons can be diagnosed in neuropathological disorders such as Alzheimer's disease [4,20,41].…”

Análise da expressão das proteínas Rab anterior à agregação proteica associada a neurodegeneração

“…Com relação aos níveis de Rab1, foi observado aumento da expressão desta proteína na substância negra, o que pode revelar um mecanismo preventivo à toxicidade que a célula está exposta, apesar de ainda não haver acúmulo de proteínas.Enquanto que no locuscoeruleus, cujos neurônios são mais susceptíveis a mudanças que conduzem a neurodegeneração (Arendt et al, 1995), a Rab1 encontra-se diminuída, assim como na região do hipocampo, demonstrando uma maior suscetibilidade dessa região também.…”

“…Porém um antigo estudo revelou que os neurônios do locus coeruleus são mais sensíveis, e em casos de doenças neurodegenerativas esta pode ser uma das primeiras regiões afetadas (Arendt, 1995).…”