Canine cognitive dysfunction and the cerebellum: Acetylcholinesterase reduction, neuronal and glial changes

Pugliese, Marco; Gangitano, Carlo; Ceccariglia, Sabrina; Carrasco, Josep L.; Fa, Aurora Del; Rodrı́guez, Manuel J.; Michetti, Fabrizio; Mascort, Joan; Mahy, Nicole

doi:10.1016/j.brainres.2006.12.090

Cited by 35 publications

(30 citation statements)

References 60 publications

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“…170 As mentioned previously, laboratory-based tasks are a challenge to translate into the veterinary clinic but several studies report success using informant-based measures. [94][95][96] Veterinarians and clinical researches can use questionnaires and have owners report on changes in behavior in the home setting 34,96,145,146 similar in some ways to questionnaires including the Mini Mental State Exam used in human clinics. 18,19 Although there are several published reports of questionnaires sensitive to cognitive and behavioral aging in pet dogs, each appears to have some success in being able to distinguish normally aging dogs from those showing abnormal behavioral changes signaling canine cognitive dysfunction.…”

Section: Cognitive Dysfunction Syndrome In Dogsmentioning

confidence: 99%

“…29 Interestingly, there is little data regarding changes in the neuroinflammatory milieu in aging dog brain despite reports of higher levels of activated microglia and astrocytosis. 145,146,172 Thus, the prevalence of cerebrovascular disease (CVD) and how it relates to white matter integrity and inflammation has yet to be determined. Overall, dogs are thought to be a good model for cerebrovascular pathology and CAA.…”

Section: Vascular Lesionsmentioning

confidence: 99%

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Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

et al. 2016

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According to the WHO, the proportion of people over 60 years is increasing and expected to reach 22% of total world's population in 2050. In parallel, recent animal demographic studies have shown that the life expectancy of pet dogs and cats is increasing. Brain aging is associated not only with molecular and morphological changes but also leads to different degrees of behavioral and cognitive dysfunction. Common age-related brain lesions in humans include brain atrophy, neuronal loss, amyloid plaques, cerebrovascular amyloid angiopathy, vascular mineralization, neurofibrillary tangles, meningeal osseous metaplasia, and accumulation of lipofuscin. In aging humans, the most common neurodegenerative disorder is Alzheimer's disease (AD), which progressively impairs cognition, behavior, and quality of life. Pathologic changes comparable to the lesions of AD are described in several other animal species, although their clinical significance and effect on cognitive function are poorly documented. This review describes the commonly reported age-associated neurologic lesions in domestic and laboratory animals and the relationship of these lesions to cognitive dysfunction. Also described are the comparative interspecies similarities and differences to AD and other human neurodegenerative diseases including Parkinson's disease and progressive supranuclear palsy, and the spontaneous and transgenic animal models of these diseases.

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Section: Cognitive Dysfunction Syndrome In Dogsmentioning

confidence: 99%

Section: Vascular Lesionsmentioning

confidence: 99%

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

et al. 2016

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“…In addition, overall neurogenesis and neuronal differentiation in the aged canine hippocampus were substantially reduced by 90-96% [24]. However, no studies have been reported on density and morphology of DCX-immunoreactive ( + ) neuroblasts in the DG of dogs, which are widely acceptable animal models for aging [17,19], at various age stages. Therefore, we examined differences in the distribution of DCX + neuroblasts in the dog DG at various ages.…”

mentioning

confidence: 99%

Comparison of Density and Morphology of Neuroblasts in the Dentate Gyrus among Variously Aged Dogs, German Shepherds

Hwang

Yoo

Park

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. Neural progenitor cells in the dentate subgranular zone (SGZ) produce new cells all through life via proliferation. We observed differences in neuroblasts using doublecortin (DCX, a marker of neuronal differentiation) in the SGZ in variously aged dogs (German shepherds). In the 1-year-old group, DCX-immunoreactive ( + ) cells were abundantly observed in the SGZ: These cells had processes extending into the molecular layer. In the 3-year-old group, DCX + cells were decreased by 53.0% compared to that in the 1-year-old group, and DCX + processes were also markedly decreased. In the 6 and 8-year-old groups, DCX + cells were decreased by 34.3% and 62.9% vs. the pre-aged group. In the 8-year-old group, DCX + cells were decreased by 86.4% compared to that in the 1-year-old group. In the 12-year-old group, DCX + cells and processes were nearly disappeared. This suggests that DCX + cells processes significantly decreased at 3 years in the SGZ of the German shepherd.

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“…Since dense core Aβ plaque formation has been associated with an acetylcholinesterase heterogeneous nucleator action [69], the relation between cerebellar pathology, acetylcholinesterase density and cognitive dysfunction has also been studied in family dogs [70]. In these animals, the late cerebellum involvement is evidenced by the absence of Aβ plaque.…”

Section: Brain Aβ Distributionmentioning

confidence: 99%

Dogs with Cognitive Dysfunction Syndrome: A Natural Model of Alzheimer’s Disease

Bosch¹,

Pugliese²,

Gimeno-Bayón³

et al. 2012

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In the search for appropriate models for Alzheimer's disease (AD) involving animals other than rodents, several laboratories are working with animals that naturally develop cognitive dysfunction. Among the animals tested, dogs are quite unique in helping to elucidate the cascade of events that take place in brain amyloid-beta (Aβ) deposition aging, and cognitive deficit. Recent innovative research has validated human methods and tools for the analysis of canine neuropathology and has allowed the development of two different approaches to investigate dogs as natural models of AD. The first approach relates AD-like neuropathy with the decline in memory and learning ability in aged housed dogs in a highly controlled laboratory environment. The second approach involves research in family-owned animals with cognitive dysfunction syndrome. In this review, we compare the strengths and limitations of housed and family-owned canine models, and appraise their usefulness for deciphering the early mechanisms of AD and developing innovative therapies.KEYWORDS: aging, Amyloid-beta, animal model, canine cognitive dysfunction syndrome, family dog, therapies. 6 Why a canine model of AD?For years, the search for appropriate animal models for Alzheimer's disease (AD) has focused on a variety of manipulations to reproduce the disease in various species, such as yeast, Drosophyla melanogaster, Caenorabditis elegans, rodents, and rabbits, with a particular interest in obtaining knockout and transgenic animals (for a review, see [1]research is currently performed in the mouse because its brain structure is somewhat similar to that of humans, and it is amenable to highly sophisticated genetic engineering. Because age-related cognitive decline is a common feature of most mammals, other laboratories have focused on the few species that naturally develop cognitive dysfunction with various Alzheimer-like characteristics. These animals include the monkey, polar bear, cat and dog [2][3][4][5]. Canine models are currently considered a useful intermediate between genetically modified mouse models and humans [6,7]. Although many of the transgenic AD models have provided insights into the molecular mechanisms of the pathology, none of them encompass all the cognitive deficits observed in AD (see Table 1). One of the first transgenic mouse AD models was the amyloid precursor protein transgenic mouse, PDAPP mouse, which develops age-dependent amyloid beta accumulation and deposition in both diffuse and fibrillar neuritic plaques in the hippocampus, cerebral cortex, and corpus callosum [8]. Other models with AD-like pathology are apolipoprotein E (ApoE) or Tau transgenic mice, and also mice in which other genes have been modified. In more sophisticated approaches, important information has been gained from crossing PDAPP and ApoE models and with mice lacking or over-expressing genes for beta-secretase, alpha-secretase, or the insulin-degrading enzyme [9,10].All these models have provided valuable information on AD pathology and on the poss...

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Canine cognitive dysfunction and the cerebellum: Acetylcholinesterase reduction, neuronal and glial changes

Cited by 35 publications

References 60 publications

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

Pathology of the Aging Brain in Domestic and Laboratory Animals, and Animal Models of Human Neurodegenerative Diseases

Comparison of Density and Morphology of Neuroblasts in the Dentate Gyrus among Variously Aged Dogs, German Shepherds

Dogs with Cognitive Dysfunction Syndrome: A Natural Model of Alzheimer’s Disease

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