pituitrin and Cognition-Disorders

Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.

Topics: Adult; Aged; Aging; Alzheimer Disease; Case-Control Studies; Circadian Rhythm; Cognition Disorders; Corticotropin-Releasing Hormone; Dehydroepiandrosterone; Dementia; Dementia, Vascular; Hippocampus; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Middle Aged; Neuronal Plasticity; Pituitary-Adrenal System; Receptors, Steroid; Stress, Physiological; Vasopressins

Posttraumatic stress disorder (PTSD) is characterized by a peculiar cognitive state. The traumatic event(s) are partly hypermemorized, partly blurred, whereas the ability to store and retrieve new information is impaired. The question is raised as to what the biological systems might be that 'carry' this cognitive paradox. Four possible candidate systems are discussed. It is concluded that understimulation of the corticosteroid receptors, particularly the glucocorticoid receptors (GRs), overactivity of the noradrenaline (NA) and vasopressin (VA) systems, and deficits in the 5-Hydroxytryptamine (5-HT) system, particularly the 5-HT(1A) system, could generate a cognitive syndrome similar to the one observed in PTSD. A dual hypothesis is launched holding that (a) in PTSD, downregulation of the 5-HT(1A) receptor system is the primary lesion, while the other dysfunctions mentioned are subsidiaries and that (b) underdevelopment of or damage to the 5-HT(1A) receptor system will make a person PTSD-prone.

Topics: Animals; Cognition; Cognition Disorders; Humans; Models, Biological; Norepinephrine; Receptor, Serotonin, 5-HT1A; Receptors, Steroid; Serotonin; Stress Disorders, Post-Traumatic; Vasopressins

Topics: Aged; Aging; Cognition Disorders; Humans; Middle Aged; Oxytocin; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Alzheimer Disease; Animals; Cognition Disorders; Dementia; Humans; Neuropeptides; Vasopressins

Mammalian neural transplantation has recently been recognized to be a valuable technique for studying normal development and regeneration in the central nervous system. In addition, the ability of grafted neurons to reinnervate damaged regions of the host brain and to ameliorate some neuroendocrine deficits, cognitive disorders and motoric dysfunctions in young adult rodents has suggested that transplantation therapy may be effective in treating human neurodegenerative diseases and neurotransmitter deficiencies related to aging. It is of particular interest that initial studies of neuron transplants in aged rodents indicate that cholinergic, dopaminergic and noradrenergic neurons all integrate to some extent with the aged brain, and that the product of this graft-host interaction is improved behavioral performance of aged subjects. The present paper critically reviews the present domain of neural transplantation, its application to studies on the properties of the aged mammalian brain and discusses the possible therapeutic use of transplants in ameliorating transmitter-specific abnormalities associated with Parkinson's disease and Alzheimer's disease.

Topics: Adrenal Medulla; Aging; Animals; Brain; Cell Line; Central Nervous System; Cognition Disorders; Fetus; Forecasting; Humans; Hypogonadism; Mammals; Movement Disorders; Neurons; Neurosecretory Systems; Neurosurgery; Neurosurgical Procedures; Peripheral Nerves; Pituitary Hormone-Releasing Hormones; Vasopressins; Vertebrates

Many of the neurochemical changes associated with aging brain, particularly lower choline acetyltransferase and higher monoamine oxidase, occur with greater severity in senile dementia, Alzheimer's type (SDAT). These alterations correlate with neuropathologic indices, e.g., the number of senile plaques and tangles. Although many different treatment techniques have been used, most have been unsuccessful. No strong data have supported the use of stimulants, Gerovital H3, or hyperbaric oxygen. Among the vasodilators, cyclandelate and hydergine may be of value in some but not most patients. Much recent work has focused on techniques to increase acetylcholine brain concentrations. To date, precursors, such as choline, seem to have very limited value. Postsynaptic treatments, e.g., physostigmine, hold more hope for future benefit, if longer acting oral preparations are developed. Other compounds, such as ACTH, vasopressin, and piracetam, may have some value but need better definition and treatment indications. Recent discoveries on the influences of lecithin on membrane fluidity and receptor binding, may affect the focus of future pharmacologic investigation.

Topics: Adrenocorticotropic Hormone; Aged; Aging; Alzheimer Disease; Arecoline; Brain Chemistry; Choline; Cognition Disorders; Cyclandelate; Electroencephalography; Humans; Memory; Methylphenidate; Pentylenetetrazole; Phosphatidylcholines; Physostigmine; Piracetam; Procaine; Vasodilator Agents; Vasopressins

Topics: Animals; Behavior, Animal; Cognition; Cognition Disorders; Electroconvulsive Therapy; Humans; Memory; Mental Disorders; Neurophysins; Oxytocin; Pituitary Hormones, Posterior; Vasopressins

Topics: Adrenocorticotropic Hormone; Aged; Aging; Amnesia; Animals; Avoidance Learning; Behavior, Animal; Cognition Disorders; Endorphins; Extinction, Psychological; Humans; Hypophysectomy; Male; Memory; Middle Aged; Peptides; Pituitary Hormones; Rats; Retention, Psychology; Vasopressins

Survival rates for cardiac arrest patients, both in and out of hospital, are poor. Results of a previous study suggest better outcomes for patients treated with vasopressin than for those given epinephrine, in the out-of-hospital setting. Our aim was to compare the effectiveness and safety of these drugs for the treatment of in-patient cardiac arrest.. We did a triple-blind randomised trial in the emergency departments, critical care units, and wards of three Canadian teaching hospitals. We assigned adults who had cardiac arrest and required drug therapy to receive one dose of vasopressin 40 U or epinephrine 1 mg intravenously, as the initial vasopressor. Patients who failed to respond to the study intervention were given epinephrine as a rescue medication. The primary outcomes were survival to hospital discharge, survival to 1 h, and neurological function. Preplanned subgroup assessments included patients with myocardial ischaemia or infarction, initial cardiac rhythm, and age.. We assigned 104 patients to vasopressin and 96 to epinephrine. For patients receiving vasopressin or epinephrine survival did not differ for hospital discharge (12 [12%] vs 13 [14%], respectively; p50.67; 95% CI for absolute increase in survival 211.8% to 7.8%) or for 1 h survival (40 [39%] vs 34 [35%]; p50.66; 210.9% to 17.0%); survivors had closely similar median mini-mental state examination scores (36 [range 19-38] vs 35 [20-40]; p50.75) and median cerebral performance category scores (1 vs 1).. We failed to detect any survival advantage for vasopressin over epinephrine. We cannot recommend the routine use of vasopressin for inhospital cardiac arrest patients, and disagree with American Heart Association guidelines, which recommend vasopressin as alternative therapy for cardiac arrest.

Topics: Aged; Arrhythmias, Cardiac; Cognition Disorders; Double-Blind Method; Epinephrine; Female; Heart Arrest; Hospitalization; Humans; Hypertension; Infarction; Male; Mental Status Schedule; Mesentery; Middle Aged; Ontario; Resuscitation; Safety; Survival Analysis; Time Factors; Treatment Outcome; Vasopressins

Topics: Adolescent; Adult; Chronic Disease; Cognition Disorders; Female; Humans; Neuropsychological Tests; Oxytocin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Vasopressins; Young Adult

Many with schizophrenia experiences deficits in social cognition, neurocognition and metacognition. Yet the biological mechanisms which may underpin these cognitive deficits are poorly understood. Two candidate causes of these deficits are disturbances in oxytocin (OT) and vasopressin (VP). To explore this we assessed plasma OT and VP in 34 schizophrenia patients and 31 healthy controls. We also concurrently assessed social cognition using the Reading the Mind from the Eyes test, neurocognition using the Wisconsin Card Sorting Test and metacognition using the Metacognitive Assessment Scale-Abbreviated. Group comparisons revealed lower plasma OT levels in the schizophrenia group. Plasma VP levels did not differ between groups. Correlations revealed that lower levels of OT were associated with poorer levels of metacognitive functioning in the schizophrenia group but not poorer social cognition or neurocognition. In a stepwise multiple regression, plasma OT level, neurocognition and social cognition contributed uniquely to the prediction of metacognition in the schizophrenia group. Results may suggest that disturbance in OT is linked with deficits in metacognition and may interact with other forms of cognitive deficits, interfering with the person's abilities to form a complex and integrated sense of self and others.

Topics: Adult; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Male; Metacognition; Neuropsychological Tests; Oxytocin; Schizophrenia; Schizophrenic Psychology; Social Behavior; Social Perception; Vasopressins; Young Adult

Adequate hydration is essential for normal brain function and dehydration induces cognitive deterioration. In addition, dehydration has emerged as a stroke risk factor. However, it is unknown whether alterations in cerebrovascular regulation are responsible for these effects. To address this issue, C57Bl/6 mice were water deprived for 24 or 48 hours and somatosensory cortex blood flow was assessed by laser-Doppler flowmetry in a cranial window. Dehydration increased plasma osmolality and vasopressin levels, and suppressed the increase in blood flow induced by neural activity, by the endothelium-dependent vasodilator acetylcholine and the smooth muscle relaxant adenosine. The cerebrovascular dysfunction was associated with oxidative stress and cognitive deficits, assessed using the Y maze. The vasopressin 1a receptor antagonist SR49059 improved the dehydration-induced oxidative stress and vasomotor dysfunction. Dehydration upregulated endothelin-1 in cerebral blood vessels, an effect blocked by SR49059. Furthermore, the endothelin A receptor antagonist BQ123 ameliorated cerebrovascular function. These findings show for the first time that dehydration alters critical mechanisms regulating the cerebral circulation through vasopressin and oxidative stress. The ensuing cerebrovascular dysregulation may alter cognitive function and increase the brain's susceptibility to cerebral ischemia.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Brain; Cerebrovascular Circulation; Cognition Disorders; Dehydration; Endothelin-1; Male; Mice; Mice, Inbred C57BL; Osmolar Concentration; Oxidative Stress; Vasopressins; Water Deprivation

Multiple sclerosis (MS) is a complex neurodegenerative disease presenting with a diversity of clinical symptoms including palsy and cognitive impairment. We present a 59-year-old woman with a history of secondary progressive MS since 1987, who was referred to our department because of recent onset of confusion and polydipsia. Initial lab tests showed mildly elevated serum sodium levels and low urine osmolality. Under water deprivation, diuresis and low urine osmolality persisted and serum sodium levels rose above 150 mmol/l. Oral desmopressin resulted in normalisation of serum sodium as well as urine osmolarity, confirming a diagnosis of central diabetes insipidus. As drug-induced diabetes could be excluded, pituitary magnetic resonance imaging (MRI) was performed. A demyelinating lesion was detected in the hypothalamus. The patient was started on oral desmopressin treatment (0.2 mg/day). Fluid intake and serum sodium levels have since remained normal. In summary, we report the rare case of a patient presenting with diabetes insipidus due to progressive MS. Diabetes insipidus should be considered in MS patients who develop new onset of polydipsia.

Topics: Atrophy; Cognition Disorders; Confusion; Diabetes Insipidus; Female; Humans; Hyponatremia; Hypothalamus; Magnetic Resonance Imaging; Middle Aged; Multiple Sclerosis, Chronic Progressive; Polydipsia; Sodium; Vasopressins

Although secondary end-organ damage in diabetes has generally been thought to result from long-term passive shunting of excess glucose through alternative metabolic pathways, recent studies have elucidated a second mechanism of pathogenesis that involves active changes in gene expression in neurons of the CNS. These changes in gene expression result in molecular and functional changes that can become maladaptive over time. In this review, we examine two neuronal populations in the brain that have been studied in human beings and animal models of diabetes. First, we discuss overactivation of magnocellular neurosecretory cells within the hypothalamus and how it relates to the development of diabetic nephropathy. And second, we describe how changes in hippocampal synaptic plasticity can lead to cognitive and behavioural deficits in chronic diabetes. Changes in neuronal gene expression in diabetes represent a new pathway for diabetic pathogenesis. This pathway may hold clues for the development of therapies that, via the targeting of neurons, can slow or prevent the development of diabetic end-organ damage.

Topics: Animals; Cognition Disorders; Diabetes Mellitus; Diabetic Nephropathies; Gene Expression; Hippocampus; Humans; Hyperglycemia; Hypothalamus; Neuronal Plasticity; Neurons; Vasopressins

Brattleboro (BB) rats are Long Evans rats with a single base pair genetic mutation that impairs their ability to synthesize vasopressin, a neurotransmitter and neurohormone. Brattleboro rats are known to have deficits in memory, emotional reactivity, motivation, attention, and social recognition, abnormalities associated with schizophrenia. Prepulse inhibition (PPI) of the acoustic startle reflex (ASR) is a measure of sensorimotor gating. Prepulse inhibition is deficient in unmedicated schizophrenia patients, and PPI deficits in schizophrenia may be related to the cognitive and behavioral abnormalities associated with this disorder. In this study we tested the hypothesis that BB rats exhibit PPI deficits analogous to those exhibited by schizophrenia patients.. In one experiment, BB rats homozygous (BB-Ho) or heterozygous (BB-Hz) for the mutated vasopressin gene were compared with normal Long Evans (LE) rats from the same breeder source. In separate studies, BB-Ho and LE rats were treated with acute or subchronic (22 days) injections of haloperidol.. Both BB-Ho and BB-Hz rats had significantly higher ASR and significantly lower PPI compared with LE rats, with BB-Ho rats exhibiting the lowest PPI among all three genotypes. Furthermore, a single subcutaneous (SC) injection of haloperidol (0.5 mg/kg) did not reverse the PPI deficits in BB rats. In contrast, daily SC administration of haloperidol for 22 days reversed PPI deficits in BB rats.. These results suggest that PPI deficient BB rats may be an important genetic model of PPI deficits, which may help elucidate genetic, pharmacologic, and pathophysiologic mechanisms underlying PPI deficits and the effects of antipsychotic drugs on PPI.

Topics: Animals; Antipsychotic Agents; Cognition Disorders; Drug Administration Schedule; Gait Disorders, Neurologic; Genotype; Haloperidol; Heterozygote; Homozygote; Inhibition, Psychological; Male; Rats; Rats, Brattleboro; Rats, Long-Evans; Reflex, Startle; Vasopressins

An old women was in an 8-year-period 9 times admitted to the hospital because of severe mental disturbances. The average serum sodium concentration was 126.25 +/- 2.43 mmol/l at the admissions; it increased to 139.44 +/- 1.40 mmol/l after intravenous infusion of hypertonic solutions accompanied with the disappearance of the mental disturbances. The patient was usually chronically hyponatremic due to the increased water intake and the insufficient water excretion. The latter was induced by the augmented vasopressin levels. The remarkable feature of the syndrome of inappropriate antidiuretic hormone secretion was its association with lowered blood level of atrial natriuretic factor accompanied by sodium, and volume depletion. Discontinuation of the exaggerated water intake resulted in the elimination of the permanent hyponatremia; no episode of water intoxication occurred during the last 3 and 1/2 years.

Topics: Aged; Atrial Natriuretic Factor; Cognition Disorders; Drinking Behavior; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Vasopressins; Water Intoxication

Topics: Cognition Disorders; Consciousness Disorders; Humans; Inappropriate ADH Syndrome; Lung Neoplasms; Male; Middle Aged; Osmolar Concentration; Vasopressins

Topics: Aged; Amitriptyline; Cognition Disorders; Depression; Female; Humans; Hyponatremia; Syndrome; Vasopressins

Topics: Amitriptyline; Cognition Disorders; Fatigue; Female; Humans; Hyponatremia; Middle Aged; Osmolar Concentration; Sodium; Syndrome; Vasopressins