Background Huntington disease (HD) is characterised by cognitive impairment, motor dysfunction and psychiatric symptoms, the latter presenting as apathy, irritability, outburst, anxiety and depression. To date neuropathological correlates for psychiatric affection have been poorly investigated in HD. In the basal forebrain two systems represent a complex morphological substrate for emotion-associated functions. The ventral striatum integrates emotional, cognitive, sensory and motor information. The extended amygdala is associated with fear, hormonal responses, stress and it is involved in addiction.
Methods In order to evaluate their impact for psychiatric affection in HD, we investigated the distribution of huntingtin aggregates and the associated neuropathology in the subareas of both systems in human HD brains by light and electron microscopical EM48-immunohistochemistry.
Results Huntingtin aggregates are abundantly patch-like expressed in the nucleus accumbens (with no difference in Calbindin-poor nor Calbindin-rich areas), ventral parts of the caudate and putamen and the olfactory tubercle, all of which areas belonging to the ventral striatum. In contrast, in the dorsal motor-associated striatum, an area exhibiting major atrophy in HD, aggregates are sparse. The subregions of the extended amygdala, the bed nuclei of the stria terminalis, the interstitial nucleus of the posterior part of the anterior commissure and the central amygdaloid nuclei also show prominent huntingtin accumulation. Electron microscopically, the aggregates are mainly detected in the neuropil, whereas intranuclear localisation occurs occasionally.
Conclusions Differential affection of the two limbic forebrain systems may help to elucidate emotional regulatory and psychiatric aspects of HD, and it may also yield information on the role of huntingtin aggregates in HD pathogenesis.
- Human HD brain
- huntingtin aggregates
- ventral striatum
- extended amygdala