ABSTRACT
Human NT cells derived from the NTera2/D1 cell line express a dopaminergic phenotype making them an attractive vehicle to supply dopamine to the depleted striatum of the Parkinsonian patient. In vitro, hNT neurons express tyrosine hydroxylase (TH), depending on the length of time they are exposed to retinoic acid. This study compared two populations of hNT neurons that exhibit a high yield of TH+ cells, MI-hNT and DA-hNT. The MI-hNT and DA-hNT neurons were intrastriatally transplanted into the 6-OHDA hemiparkinsonian rat. Amelioration in rotational behavior was measured and immunohistochemistry was performed to identify surviving hNT and TH+ hNT neurons. Results indicated that both MI-hNT and DA-hNT neurons can survive in the striatum, however, neither maintained their dopaminergic phenotype in vivo. Other strategies used in conjunction with hNT cell replacement are likely needed to enhance and maintain the dopamine expression in the grafted cells.
Subject(s)
Cell Transplantation/physiology , Dopamine/physiology , Parkinson Disease, Secondary/physiopathology , Receptors, Dopamine D1/physiology , Animals , Apomorphine/toxicity , Behavior, Animal/drug effects , Cell Line , Dopamine Agonists/toxicity , Graft Survival , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Oxidopamine , Parkinson Disease, Secondary/chemically induced , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D1/genetics , Stereotyped Behavior/drug effects , Sympatholytics , Tyrosine 3-Monooxygenase/biosynthesis , Tyrosine 3-Monooxygenase/geneticsABSTRACT
The mitochondrial toxin, 3-nitropropionic acid (3-NP), produces motor dysfunction and striatal atrophy in rats. However, rat strain and method of administration may contribute to variability in the deficits caused by 3-NP toxicity. To evaluate this, changes in nocturnal spontaneous locomotor activity from chronic administration of 3-NP using an osmotic mini pump, were examined in the Lewis rats. Lewis rats were treated with 3-NP or saline for 2 days and behavior was tested daily for a 15 day period. Animals receiving 3-NP displayed significantly less spontaneous activity than animals in the saline group. 3-NP treated animals also weighed significantly less when compared to saline treated animals. These results demonstrate that even though there were no significant alterations in overt anatomical pathology, even short-term exposure to 3-NP produced significant effects. This short-term administration may present a potential paradigm for examination of sub-threshold neurotoxicity.
Subject(s)
Behavior, Animal/drug effects , Convulsants/administration & dosage , Nitro Compounds/administration & dosage , Propionates/administration & dosage , Animals , Body Weight/drug effects , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism , Drug Administration Schedule , Glial Fibrillary Acidic Protein/metabolism , Immunohistochemistry/methods , Male , Motor Activity/drug effects , Rats , Rats, Inbred Lew , Time FactorsABSTRACT
Infants who have almost died of sudden infant death syndrome (SIDS) and infants who are siblings of SIDS victims constitute groups at increased risk for SIDS. Management dilemmas are common among physicians caring for these infants. To assess the usefulness of hypoxia (17% oxygen) and hypercapnea (3% carbon dioxide) challenge tests as predictors of outcome, we reviewed the records of 102 infants who underwent these tests. During hypoxia tests, we found that periodic breathing and respiratory pauses frequently developed among the infants in these high-risk groups, but also developed among control infants. During hypercapnea testing, some infants failed to increase their minute ventilation (usually measured by volume of breath X breaths per minute), but control infants showed this poor response just as often as high-risk infants. Our findings suggest that hypoxia and hypercapnea stress tests are of limited usefulness in planning management of infants at risk for SIDS.
Subject(s)
Hypercapnia/physiopathology , Hypoxia/physiopathology , Sudden Infant Death/physiopathology , Humans , Infant , Infant, Newborn , Risk , Sudden Infant Death/geneticsABSTRACT
CO2 chemoreceptor function was assessed during natural sleep and following the administration of 100 mg/kg of chloral hydrate to 26 puppies. With chloral hydrate-induced sleep, there were no significant changes in ventilation or in CO2 chemoreceptor response. The ventilation and CO2 chemoreceptor response of a group of infants in natural sleep were compared with those of a group receiving 50 mg/kg of chloral hydrate. Tidal volume O2 consumption, and CO2 elimination were slightly higher in the group given chloral hydrate. There was no difference in the CO2 chemoreceptor response. The proportion of time spent in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep in chloral hydrate-induced sleep was similar to that occurring in natural sleep. Use of chloral hydrate stabilizes O2 consumption sleep. Use of chloral hydrate stabilizes O2 consumption and CO2 production, and it greatly facilitates the assessment of chemoreceptor function in infants. The CO2 chemoreceptor response appears not to be altered in puppies or infants.
