3.1 INTRODUCTION 3.1 INTRODUCTION

Age-related changes in the CNS or PNS may result in decreased or increased activity of neural tissue with corresponding signs of altered neurological or neuroendocrine function. A skilled clinician can determine the site of the changes from the neurological signs exhibited by an animal.

Reduced protein synthesis within cells is one of the main causes of age-related declines in tissue function and some authors believe that modification of neuroendocrine function offers the best prospect for delaying and reversing ageing changes (Meites 1993).

Modification of neuroendocrine function is probably one of the mechanisms by which calorie-restricted diets slow down ageing changes in body tissues, inhibit the development of disease and neoplasia, and significantly prolong the lifespan of rats and mice. Calorie-restricted diets decrease hormone secretion (in particular growth hormone and insulin-like growth factor 1) and also alter hormone receptor sensitivity, reduce whole-body metabolism (though basal metabolic rate per unit lean body mass remains the same) and lower gene expression.

As further support of this hypothesis the administration of hormones thymic peptides and some drugs can improve declining immune function thus improving resistance to infections, neoplasia and autoimmune disorders

In old dogs the administration of clonidine (an a 2-adrenergic agonist) increases the pulsatile secretion of growth hormone returning it to a young dog type of pattern. Furthermore administration of clonidine with growth hormone releasing hormone for 10 days significanily increases both the peak concentration and total amount of growth hormone released. A rapid radio-immunoassay for growth hormone in the dog has been described (Cocola et al. 1976).

Maladaptive responses of the neuroendocrine system to stressful stimuli (particularly in the hypothalamic-pituitary-adrenocortical system) are thought to accelerate the ageing process and reduce longevity. One study in rats suggests that longevity is inversely related to hyperactivity to stress and that this is genotype dependent. Basal cortisol levels have been reported to be increased in dogs and to be related to cognitive dysfunction associated with ageing.

During ageing, humans, rats and dogs have been shown to have hypercortisolaemia and diffuse Alzheimer's-like brain lesions (extracellular A4-amyloid deposits and intracellular fibrillar structures (TAU-protein) called neurofibrillary tangles) and neuronal decay have been reported to occur in dog brains (Cummings et al. 1993; Morys 1994). Recently a direct correlation has been demonstrated between behaviour changes as determined by cognitive tests and the severity of these pathological changes in beagles and these workers have suggested that cushingoid dogs might be a useful model for the study of Alzheimer's disease in humans (Ruehl, W.W. 1995, personal communication).

Free radical damage may play a part in the age-related changes in catecholamine neurones in the hypothalamus and in the neurotransmission of catecholamines, acetylcholine and peptide co-transmitters. Changes in receptor-site numbers or sensitivity may decrease secretion from cells which are otherwise still capable of manufacturing hormones.