Neuropathology of Aging in Cats and its Similarities to Human Alzheimer’s Disease

Elderly cats develop age-related behavioral and neuropathological changes that ultimately lead to cognitive dysfunction syndrome (CDS). These neuropathologies share similarities to those seen in the brains of humans with Alzheimer’s disease (AD), including the extracellular accumulation of ß-amyloid (Aβ) and intraneuronal deposits of hyperphosphorylated tau, which are considered to be the two major hallmarks of AD. The present study assessed the presence and distribution of Aβ and tau hyperphosphorylation within the cat brain (n = 55 cats), and how the distribution of these proteins changes with age and the presence of CDS. For this, immunohistochemistry was performed on seven brain regions from cats of various ages, with and without CDS (n = 10 with CDS). Cats accumulate both intracytoplasmic and extracellular deposits of Aβ, as well as intranuclear and intracytoplasmic hyperphosphorylated tau deposits. Large extracellular aggregates of Aβ were found in elderly cats, mainly in the cortical brain areas, with occasional hippocampal aggregates. This may suggest that these aggregates start in cortical areas and later progress to the hippocampus. While Aβ senile plaques in people with AD have a dense core, extracellular Aβ deposits in cats exhibited a diffuse pattern, similar to the early stages of plaque pathogenesis. Intraneuronal Aβ deposits were also observed, occurring predominantly in cortical brain regions of younger cats, while older cats had few to no intraneuronal Aβ deposits, especially when extracellular aggregates were abundant. Intracytoplasmic hyperphosphorylated tau was found within neurons in the brains of elderly cats, particularly in those with CDS. Due to their ultrastructural features, these deposits are considered to be pre-tangles, which are an early stage of the neurofibrillary tangles seen in AD. The largest numbers of pre-tangles are found mainly in the cerebral cortex of elderly cats, whereas lower numbers were found in other regions (i.e., entorhinal cortex and hippocampus). For the first time, intranuclear tau was found in both phosphorylated and non-phosphorylated states within neurons in the cat brain. The highest numbers of intranuclear deposits were found in the cortex of younger cats, and this tended to decrease with age. In contrast, elderly cats with pre-tangles had only occasional or no nuclear labelling.

Neuroisualization of Pharmaco-EEG Effects of Leutragine by Normalized Cat Brain Electrograms

The central mechanisms of leutragine during inhalational administration were investigated by analyzing normalized brain cat electrograms obtained by the method of Fast Fourier Transform (FFT). According to the conducted pharmaco-electroencephalography (pharmaco-EEG) analysis, Leutragine demonstrates a maximum effect on the parameters of brain electrograms approximately 30 minutes after administration followed by its persistence for about 2 hours. The observed effect is characterized predominantly by a deprimation of all analyzed rhythms compared to the initial values. Normalized brain electrograms (NBE) are less pronounced in the area of the hippocampus, although being more pronounced in the area of the cingulate gyrus and posterior hypothalamus. This may indicate the leucinencephaline regulation of intracentral relations of the brain. The most significant effects obtained in high-frequency β- and γ-rhythms (about 20–25, 40 and 60 Hz) indicate an increase in the γ-activity of interneurons and inhibition of pyramidal cells, which may indicate an anti-anxiety, antidepressant, antiepileptic, analgesic and similar actions of the substance under study. The NBE parameters were found to identical under the action of Leutragine and the derivatives of gamma-aminobutyric acid (glutamine, gabapentin, pregabalin, and phenibut), mainly at frequencies of about 40 and 60 Hz. Similar NBE parameters were obtained under the action of nootropics (semax), which is expressed in the activation of the hippocampus and the hypothalamus posterior at frequencies of about 60–65 Hz. This suggests that the action of Leutragine reflects the mechanisms of GABAergic modulation of the hippocampus and prefrontal neocortex, at the same time as having a positive effect on mental performance, memory consolidation and cognitive function. Leutragine can be used to model and study mechanisms exhibiting a positive effect in the treatment of diseases caused, among other things, by the new coronavirus infection COVID-19.

New Biomedical Approaches in Information and Cognitive Technologies of Psychopathology Modeling

Analysis of intracentral brain relationships, cognitive and psychopathological processes in animals by means of pharmacological modulation is an optimal method of cognition, determining the possibilities of correlation with similar processes in humans. New methods and approaches to biomodulation of psychopathologies, based on the principles of pharmaco-EEG standardization using fast Fourier-transformed brain electrograms and elements of systemic behavior, allow to identify quantitative parameters of fundamental mechanisms of neuropsychoactive agents in the cat brain.

Principles of age-related changes in the canine and feline brain

In the aged dog and cat, especially dog, a cognitive decline develops naturally in many different domains, but at the same time it also exhibits human-like individual variability in the aging process. In the aging dog and cat brain lesions develop spontaneously. Dogs share some morphological characteristics with those of Alzheimer’s disease in man. The canine brain with its plaques and tangles which show oxidative changes, forms a spontaneous model for understanding the early changes and their interrelationships in Alzheimer’s disease. Additionally, the aged dog represents a useful model for the development of preventive or therapeutic interventions to improve aged brain function. These interventions can then be translated into human clinical trials.