Dogs get dementia too and may help save humans
The canine brain recapitulates many important structural features of the human brain, including an over-developed neocortex, gyral folding patterns and lobar organization. The canine medial temporal lobe is also unique for exhibiting ‘two hippocampi’ per hemisphere, an upper ‘rodent-like’ and lower ‘human-like’ hippocampus. Surprisingly, RNG research has revealed that upper and lower canine hippocampal regions have distinct neurogenic properties.
Interestingly,the great majority of canine anatomical variance only arose in the last 200 years due to unnatural selection in the form of human-induced breed pressure. This has been accompanied by behavioural adaptation, with the classic dog breed families denoted by functional attributes such as ‘pointers’, ‘retrievers’, ‘herders’, ‘guarders’, ‘hunters’ and so forth.
Along with this vast physical variability in body shape and size is a diversity of skull shapes. Using a measure called the ‘cepalic index’, RNG found that more pug-like dogs (with shorter cuboid skulls) have undergone a major reorganization of their brain. The overall axis of the pug-like brain was rotated forwards, and the olfactory lobe tended to relocate deeper down the base of the skull. Canine morphological plasticity therefore also appears to have translated into an amazing degree of brain plasticity.
One of the reasons dogs are so valued by their owners is that they celebrate our happiness and console our despair. The modern dog is uniquely sensitive to human emotion and is the only species (apart from humans) to spontaneously attend to the eye region of the human face. Dogs are, for example, able follow ‘eye-only’ commands and react differently when human gestures are preceded by a non-verbal signal of communicative intent.
Dogs also exhibit the full range of emotional states themselves. Prof Paul McGreevy of the Faculty of Veterinary Science, is leading research to understand the phenomenon of depression-like syndrome in shelter dogs. These animals appear to exhibit elements of lethargy, anhedonia, appetite loss and locomotor slowing.
With advanced age, canines experience many of the same brain problems as humans, including development of a dementia-like syndrome called Canine Cognitive Dysfunction (CCD). CCD has several clinical features that resembles human dementia at different stages: memory loss, disorientation, agitation, sleep-wake dysfunction, incontinence and abnormal motor behavior. The movie below shows one of the most characteristics features of CCD, ‘staring blankly at walls’. Like in humans, the prevalence of CCD rises exponentially in dogs after 8 years of age. Approximately 10% of dogs aged 8 years have CCD, rising to 25% in dogs aged 14 years.
Yet only 1-in-10 dogs with CCD are being diagnosed because of the low level of awareness of this syndrome amongst owners or veterinarians. In response, RNG developed the Canine Cognitive Dysfunction Rating scale (CCDR) as way to properly test for and assess CCD. The CCDR is now available online to help diagnose your dog.
With ageing, dogs also develop Alzheimer disease pathology throughout the hippocampus and cortical areas, including amyloid plaques. Such canine brain amyloid has 100% molecular homology with the human protein and 98% homology for the antecedent amyloid precursor protein.
CCD is therefore a major research focus at RNG as it presents us with the rare opportunity to understand dementia in a naturalistic animal model with many translational advantages.
In order to better understand CCD we found a missing link in the field was a method of assessing memory in pet dogs in a way that was both dog-friendly and accurate. RNG therefore developed and validated the Canine Sand Maze as a practical and accurate method of assessing canine spatial learning, working memory and delayed recall in pet dogs.
The Canine Sand Maze takes about 3 hours to complete at our specialist facility at the University of Sydney’s Faculty of Veterinary Science. It first involves a number of learning trials, where the dog is taught to dig up a food treat buried in a large pool of sand that has powdered food mixed through it (to disguise the scent!). The dog then takes a break for 1.5 hours and comes back for the key ‘probe’ trial – on this occasion we are testing whether the dog moves preferentially to the old learnt location, rather than a new location where we have secretly buried the food. We can conclude that dogs who navigate towards the learnt location have intact spatial memory rather than are just trying to sniff it out.
The videos below show examples of a young dog that successfully completes the Canine Sand Maze probe trial (and then tries to escape!), and an old dog that has no delayed memory of the learnt food location. It’s easy to work out which one is which.
Canine Stem Cells
RNG has developed a highly specialized technique for generating neurons from a small sample of adult canine skin. We do this by converting adult skin stem cells (found in all mammalian skin) into a type of neural stem cell (NSCs). In addition, we have transplanted these canine skin-derived NSCs into rats with age-related memory dysfunction. This type of treatment reverses the rats’ memory problems and cells survive and engraft into the host brain.
In all studies so far, transplantation of these cells has been safe – rodents have shown no side effects from the treatment or developed brain tumors.
DOGS +CELLS Trial of Cell Therapy to Help Beat CCD
We are therefore at the exciting stage in our research where we aim to trial, for the first time, whether Canine Cognitive Dysfunction in older dogs can be treated by brain transplantation of NSCs generated from the dog’s own skin.
Dogs as Natural Models of Humankind’s Noble Qualities and Greatest Health Challenges
Beyond CCD, dogs exhibit a wide range of neurodegenerative, neurological and neuropsychiatric conditions. There is for example an established body of research investigating canine epilepsy, as well as emerging interest in hereditary parkinsonism, stroke and so forth.
Interestingly, secular trends in human health and demographics such as population ageing and the rising prevalence of obesity and metabolic syndrome disorders are also occurring in the community dog population. Dogs often eat what we eat, exercise as much as we do, and are exposed to a similar environment that we live in. Accordingly, dogs present us with a fascinating opportunity to study physical-mental-health interactions that are rising in prominence in human health.
Dogs also present us the rare chance to systematically study the characteristics we normally associate with noble human virtues. Loyalty, fidelity, companionship, empathy, happiness and even unconditional love, are all traits that companion dogs express naturally and are almost impossible to ‘model’ in rodents. At a higher level, social cognitive ideas such as ‘theory of mind’, group membership, and interpersonal dynamics are completely new frontiers for canine research.
Overall, the canine brain represents an unique opportunity to study a range of positive psychological states as well as naturalistic models of neuropsychiatric disorders. The RNG Canine Translational Neuroscience Program aims to expand and accelerate this research through collaborations with experts in basic science and clinical research from within the Brain and Mind Research Institute, as well as the University of Sydney’s Faculty of Veterinary Science, and leading national, international and industry-based researchers.
Welfare of our dogs is always a primary consideration – through this research we aim to improve both canine and human health.
1. Bertolini G 2011. ‘Canine ischaemic stroke: current status and future directions.’ The Veterinary Journal, 188: 9-10.
2. Head E, McCleary R, Hahn F, Milgram N, Cotman CW. 2000 ‘Region-specific age at onset of b-amyloid in dogs. Neurobiology of Aging.’ 21, 96.
3. Lowe A, Dalton M, Sidhu K, Sachdev P, Reynolds B, Valenzuela M. Dissociable Neurogenic Stem Cell Differences in the Dorsal and Ventral Adult Canine Hippocampus. In preparation.
4. Neff MW, Rine J. 2006 ‘A Fetching Model Organism.’ Cell 124, 229-231
5. O’Brien DP, Johnson GS, Schnabel RD, Khan S, Coates JR. 2005 ‘Genetic Mapping of Canine Multiple System Degeneration and Ectodermal Dysplasia Loci.’ Journal of Heredity, 96 (7) 727-734.
6. Podell M, Fenner WR, Powers JD. (1995) ‘Classification in Dogs from a Non-Referral-Based Population. J American Vetrinary Medical Association, 206: 1721e8.
7. Roberts T, McGreevy P, Valenzuela M. (2010). “Human Induced Rotation and Reorganization of the Brain of Domestic Dogs.” PLoS One 5(7): e11946.
8. Salvin HE, McGreevy PD, Sachdev PS, Valenzuela MJ. 2010 ‘Under Diagnosis of Canine Cognitive Dysfunction: A cross=sectional survey of Older Companion Dogs. The Veterinary Journal, 184 (3) 277-281.
9. Salvin HE, McGreevy PD, Sachdev PS, Valenzuela MJ. 2011a ‘The Canine Cognitive Dysfunction Rating Scale (CCDR): A data-driven and ecologically relevant assessment tool.’ The Veterinary Journal, 188 331-336.
10. Salvin HE, McGreevy PD, Sachdev PS, Valenzuela MJ. 2011b ‘The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs.’ Journal of the Experimental Analysis of Behaviour.’ 95 109-118.
11. Selkoe D. 1999 ‘Translating cell biology into therapeutic advances in Alzheimer’s disease.’ Nature 399, A23-A31.
12. Téglás E, Gergely A, Kupán K, Miklósi A, Topál J. 2012 ‘Dogs’ Gaze Following is Tuned to Human Communicative Signals.’ Current Biology 22, 1-4.