healthy neuron dendrite vs diseased neuron dendrite

They also exhibit a progressive age-related decline in hippocampus-dependent working and spatial memory tasks, decreased hippocampal volume, and several AD-like pathological changes compared to age-matched wild type (WT) counterparts. Increased levels of HNE protein adducts occur in the brains of AD patients at both early and late stages of disease progression and likewise, Aldh2 knockout (KO) mice exhibit increased levels of HNE protein adducts. Oxidative stress has been implicated as a primary driving force in AD pathogenesis and we have developed an oxidative stress-based model of age-related cognitive impairment based on gene deletion of aldehyde dehydrogenase 2 (ALDH2), an enzyme important for the detoxification of endogenous aldehydes (e.g., 4-hydroxynonenal, HNE) arising from lipid peroxidation. Animals that develop pathology because they age, rather than because they are genetically programmed, would facilitate the assessment of intervention strategies that relieve AD symptoms and slow/reverse the underlying disease process. In contrast, the study of late-onset (sporadic) Alzheimer’s disease (LOAD) lacks animal models that mirror age-related progression of AD pathologies. However, genetic changes account for only a small proportion of AD cases (1–5%). There are numerous transgenic mouse models of Alzheimer’s disease (AD) which exhibit neuropathological changes dependent on the overexpression of mutant human genes linked to early onset, familial AD. This is in keeping with studies showing that lesions to the dorsal hippocampus impair primarily cognitive memory whereas ventral hippocampal lesions cause deficits in stress, emotion, and affect. These data suggest a region-specific vulnerability to oxidative stress-induced damage and/or a major and specific reduction in synaptic input to the pyramidal neurons of the dorsal hippocampus. In contrast, pyramidal arborization in the vCA1 and primary sensory cortex were only minimally reduced in KO versus WT mice. As well, spine density along dorsal CA1 apical dendrites was significantly lower in KO versus WT. Compared to WT controls, the morphology and complexity of dCA1 pyramidal neurons from KOs showed significant reductions in apical and basal dendritic length, dendrite intersections, ends, and nodes. Four pyramidal neurons were traced per mouse in each region, followed by branched structured analysis and Sholl analysis. Dendritic morphology was quantitatively analyzed following Golgi-Cox staining using 9 WT mice (108 neurons) and 15 KO mice (180 neurons). Here we performed morphometric analyses in the dorsal and ventral hippocampal CA1 regions (dCA1 and vCA1) as well as in overlying primary sensory cortex to determine if altered neuronal structure can help account for the cognitive impairment in 12-month old KO mice. Compared to wildtype (WT) mice, the knockout (KO) mice exhibit a progressive decline in recognition and spatial memory and AD-like pathologies. This enzyme is important for the detoxification of endogenous aldehydes arising from lipid peroxidation. Oxidative stress promotes LOAD, so we have developed an oxidative stress-based model of age-related cognitive impairment based on gene deletion of aldehyde dehydrogenase 2 (ALDH2). The study of late-onset (sporadic) Alzheimer’s disease (LOAD) has lacked animal models where impairments develop with aging.

Healthy neuron dendrite vs diseased neuron dendrite