beta-endorphin and Nerve-Degeneration

Exogenous angiotensin II (AII) administration produces a robust drinking response, even in water-satiated rats. All receptors are located in the hypothalamus and circumventricular organs (CVOs). Early postnatal administration of monosodium glutamate (MSG) produces hypothalamic/CVO damage. Therefore MSG might damage hypothalamic/CVO neurons important for producing the drinking response to AII. Few noninvasive procedures or tests exist to indicate the presence of a MSG lesion. Thus, the present study sought to determine whether altered water consumption after AII administration would signify the presence of a MSG lesion, as well as to demonstrate hypothalamic/CVO involvement in AII-induced drinking. Adult rats (dosed as neonates with MSG or saline) were given various doses of AII and the beta-adrenergic agonist isoproterenol. MSG-treated rats drank significantly less water after 100 ug/kg, sc AII than control rats. MSG-treated rats also had an unexpectedly high mortality after 100 ug/kg, sc isoproterenol. Thus, measurement of the drinking response may be a sensitive, noninvasive method for detecting neurotoxic damage to hypothalamic/CVO sites critical for the central action of AII.

Topics: Angiotensin II; Animals; Animals, Newborn; beta-Endorphin; Blood Glucose; Brain Mapping; Cerebral Ventricles; Dose-Response Relationship, Drug; Drinking; Eating; Hypothalamus; Isoproterenol; Male; Nerve Degeneration; Rats; Rats, Sprague-Dawley; Sodium Glutamate

Cerebrospinal fluid (CSF) levels of several neuropeptides have been suggested as candidate markers in neurodegenerative disorders. We have examined the levels of corticotropin-releasing hormone (CRH), beta-endorphine (BEND), delta sleep-inducing peptide (DSIP), somatostatin (SRIF), and neuropeptide Y (NPY) in CSF samples obtained under highly standardized conditions from healthy aged controls and from patients suffering from Alzheimer's disease (AD) or vascular dementia (VAD). The influence of some potentially confounding factors was evaluated. CRH and BEND were markedly decreased in both AD and VAD patients, and BEND levels correlated negatively with degree of dementia within the patient population. SRIF was decreased in both AD and VAD patients. DSIP was slightly increased in AD, but not in VAD. NPY did not differ between groups. For none of the peptides did CSF concentrations correlate significantly with duration of illness, nor, with the exception of BEND, with its degree. Present data do not support the hypothesis that specific neuropeptide changes occur in different neurodegenerative disorders, but are in agreement with previous reports suggesting that neuropeptide systems are differentially affected by neurodegeneration.

Topics: Aged; Alzheimer Disease; beta-Endorphin; Brain; Corticotropin-Releasing Hormone; Delta Sleep-Inducing Peptide; Dementia, Vascular; Female; Humans; Male; Nerve Degeneration; Neuropeptides; Somatostatin; Spinal Puncture

Neonatal administration of monosodium glutamate (MSG) produces necrosis of circumventricular structures, including perikarya in the medial-basal hypothalamus that contain beta-endorphin (BEND) and met-enkephalin. Since neonatal MSG treatment alters morphine analgesia, the present study examined neonatal MSG effects upon opioid analgesia observed following either BEND or d-ala d-leu enkephalin (DADL). Rats treated with either MSG or vehicle over the first ten post-natal days, were surgically prepared with a lateral ventricle cannula at 100 days of age. Respective groups received central injections of either BEND (0, 0.1, 0.5 or 1.0 microgram) or DADL (0, 4, 20 or 40 micrograms), and jump thresholds were assessed 15, 30, 45 and 60 min thereafter. Following testing, selected MSG-treated and control animals were prepared for BEND immunocytochemistry. While the magnitude, duration and sensitivity of BEND analgesia on the jump test failed to differ between groups, MSG-treated rats displayed a 10-fold leftward shift in sensitivity and a 200-300% increase in the magnitude of DADL analgesia. Immunocytochemical analysis indicated that MSG treatment depleted perikarya in the medial-basal hypothalamus, periventricular thalamic fibers and periaqueductal gray terminal fields that contained BEND. The differential effects of MSG treatment upon opiate and opioid analgesia are discussed in terms of possible alterations in opiate receptor subpopulations.

Topics: Analgesia; Animals; Animals, Newborn; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Brain Chemistry; Dose-Response Relationship, Drug; Electroshock; Endorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Female; Glutamates; Immunoenzyme Techniques; Nerve Degeneration; Rats; Rats, Inbred Strains; Reflex; Sodium Glutamate